Dengue infection in mice inoculated by the intracerebral route: neuropathological effects and identification of target cells for virus replication.

Dengue is an important arboviral infection, causing a broad range symptom that varies from life-threatening mild illness to severe clinical manifestations. Recent studies reported the impairment of the central nervous system (CNS) after dengue infection, a characteristic previously considered as atypical and underreported. However, little is known about the neuropathology associated to dengue. Since animal models are important tools for helping to understand the dengue pathogenesis, including neurological damages, the aim of this work was to investigate the effects of intracerebral inoculation of a neuroadapted dengue serotype 2 virus (DENV2) in immunocompetent BALB/c mice, mimicking some aspects of the viral encephalitis. Mice presented neurological morbidity after the 7th day post infection. At the same time, histopathological analysis revealed that DENV2 led to damages in the CNS, such as hemorrhage, reactive gliosis, hyperplastic and hypertrophied microglia, astrocyte proliferation, Purkinje neurons retraction and cellular infiltration around vessels in the pia mater and in neuropil. Viral tropism and replication were detected in resident cells of the brain and cerebellum, such as neurons, astrocyte, microglia and oligodendrocytes. Results suggest that this classical mice model might be useful for analyzing the neurotropic effect of DENV with similarities to what occurs in human.

AIM2 inflammasome is associated with disease severity in tegumentary leishmaniasis caused by Leishmania (V.) braziliensis.

The inflammasome is a multiprotein signalling platform involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated gene and protein expression of the inflammasome molecules AIM2 and NLRP3 in active lesions from patients with L. (V.) braziliensis-associated tegumentary leishmaniasis (TL) and correlated these findings with the clinical presentations and responses to therapy. Real-time PCR assays showed a significantly higher AIM2 gene expression in mucosal leishmaniasis (ML) compared with that in cutaneous leishmaniasis (CL). Additionally, AIM2 mRNA expression was significantly higher in lesions from poor responders than in lesions from good responders. In situ protein quantification analyses revealed greater AIM2 expression in ML lesions than in CL lesions. The percentage of AIM2-producing cells was higher in poor responders than in good responders. Although not quite significant, IL-1ß+ cells were slightly more prominent in poor responders than in good responders. Similar results were observed when patients were evaluated according to clinical form. GP63 immunostaining was identified in all samples, but no significant variation between mucosal and cutaneous lesions was observed. GP63 could be associated with reduced NLRP3 inflammasome expression in CL and ML patients. Taken together, these data demonstrate that AIM2 is an important component of the inflammasome in TL patients and is directly associated with the severity of lesions.

Peripheral effects induced in BALB/c mice infected with DENV by the intracerebral route.

The lack of an immunocompetent animal model for dengue mimicking the disease in humans is a limitation for advances in this field. Inoculation by intracerebral route of neuroadapted dengue strains in mice is normally lethal and provides a straightforward readout parameter for vaccine testing. However, systemic effects of infection and the immune response elicited in this model remain poorly described. In the present work, BALB/c mice infected by the intracerebral route with neuroadapted DENV2 exhibited several evidences of systemic involvement. DENV-inoculated mice presented virus infective particles in the brain followed by viremia, especially in late stages of infection. Infection induced cellular and humoral responses, with presence of activated T cells in spleen and blood, lymphocyte infiltration and tissue damages in brain and liver, and an increase in serum levels of some pro-inflammatory cytokines. Data highlighted an interplay between the central nervous system commitment and peripheral effects under this experimental condition.

Results after supracricoid horizontal partial laryngectomy.

OBJECTIVES: This study analyzed oncological and functional results of supracricoid horizontal partial laryngectomy. METHODS: A retrospective study was conducted involving 20 patients with squamous cell carcinoma (SCC) of the larynx who underwent SCPL between 1996 and 2005 in Faculty of Medical Sciences of Santa Casa Hospital of Sao Paulo, Brazil. There were 18 male and 2 female patients with ages ranging from 39 to 74 years (median=58 years), of whom 19 were smokers and 14 alcoholics. The tumors were present in the glottis in 16 cases and supraglottis in 4; 5 were stage I or II and 15 were stage III or IV. We analyzed treatment given when rehabilitation was unsuccessful, oncological results of SCPL, including local and regional recurrences, time to recurrence and treatment given, distal metastases, global survival, survival free of disease, and appearance of second primary tumors. We also calculated the index of functional preservation of the larynx. RESULTS: Rehabilitation of swallowing capabilities and speech was achieved in 18 patients. Removal of the tracheostomy varied between 1 and 9 months. Rehabilitation was unsuccessful in two patients. Three patients required a total laryngectomy, two for unsuccessful rehabilitation and one for recurrence. The preservation of a functional larynx was 85%, with 10% of patients requiring a total laryngectomy after failed rehabilitation. CONCLUSIONS: Supracricoid horizontal partial laryngectomy is an efficient surgical oncology technique that yields good functional results for the treatment of laryngeal cancer.

Surgically assisted maxillary expansion in adults: prospective study.

The purpose of this research was to carry out a prospective clinical study of patients with transverse maxillary deficiency, orthopaedically expanded after minimum osteotomies of the zygomatic pillars and the median palatine suture, with quantitative assessment of the stability of the transverse dimensions of the maxilla. The distance between the superior canines and the first superior molars was measured six times during the clinical experiment. The desired expansion was achieved by 15 days postoperatively for all patients. After one year of follow-up, clinical measurements showed a relapse rate of 23% in the superior canine area and 18% in the superior first molar area.

Amidine derivatives and Leishmania amazonensis: an evaluation of the effect of nitric oxide (NO) production on the parasite-macrophage interaction.

Previous work has demonstrated that N-N'-diphenyl-R-benzamidine was highly effective against Leishmania amazonensis promastigotes/axenic amastigotes and Trypanosoma evansi trypomastigotes and the compound with a methoxy substituent, was the most effective derivative in the parasite-macrophage interaction. Comparative analysis of the nitric oxide (NO) released from the culture infection's supernatant showed the amidine to be less effective than pentamidine Isethionate as a reference drug. Additionally, in order to verify if the methoxylated derivative interferes with NO production by L. amazonensis, the effect of the amidine on the constitutive nitric oxide synthase (cNOS) purified from parasites, was examined, but demonstrated less activity in comparison with the reference drug. This data contributes to studies concerning the metabolic targets present in Leishmania parasites for leishmanicidal drugs.

Long-term follow-up of co-infected HIV and Trypanosoma cruzi Brazilian patients.

Three cases of Trypanosoma cruzi-HIV co-infected haemophiliacs are described. Parasitological (xenodiagnosis, haemoculture, PCR) and immunological (CD4+ and CD8+ T cell counts, in vitro lymphoproliferative responses) studies were performed. Hybridization of isolated parasites with a specific probe confirmed the T. cruzi aetiology. We observed that despite the high parasitaemia, no clinical or parasitological evidence of T. cruzi reactivation was detected. CD4+ T cells decreased with time in two patients and the lymphocyte proliferative response to T. cruzi was very low in all patients. These data suggest that T. cruzi infection may have a long silent course in immunosuppressed HIV patients. Therefore, this parasitic infection should be investigated in any AIDS patient coming from areas endemic for Chagas' disease.

Cell populations in lesions of cutaneous leishmaniasis of Leishmania (L. ) amazonensis- infected rhesus macaques, Macaca mulatta

The cellular nature of the infiltrate in cutaneous lesion of rhesus monkeys experimentally infected with Leishmania (L.) amazonensis was characterized by immunohistochemistry. Skin biopsies from infected animals with active or healing lesions were compared to non-infected controls (three of each type) to quantitate inflammatory cell types. Inflammatory cells (composed of a mixture of T lymphocyte subpopulations, macrophages and a small number of natural killer cells and granulocytes) were more numerous in active lesions than in healing ones. T-cells accounted for 44.7 +/- 13.1 of the infiltrate in active lesions (versus CD2+ = 40.3 +/- 5.7 in healing lesions) and T-cell ratios favor CD8+ cells in both lesion types. The percentage of cells expressing class II antigen (HLA-DR+) in active lesions (95 +/- 7.1) was significantly higher (P < 0.005) from the healing lesions (42.7 +/- 12.7). Moreover, the expression of the activation molecules CD25 (@ 16), the receptor for interleukin-2, suggests that many T cells are primed and proliferating in active lesions. Distinct histopathological patterns were observed in lesions at biopsy, but healing lesions contained more organized epithelioid granulomas and activated macrophages, followed by fibrotic substitution. The progression and resolution of skin lesions appears to be very similar to that observed in humans, confirming the potential for this to be used as a viable model to study the immune response in human cutaneous leishmaniasis.

Short-term intensive consolidation therapy after all-trans retinoic acid in acute promyelocytic leukemia.

Complete remission induced by all-trans retinoic acid (ATRA) in acute promyelocytic leukemia is short lived, and several consolidation chemotherapy courses usually are given to reduce the relapse rate. To assess the value of short-term intensive consolidation, 38 patients with newly diagnosed acute promyelocytic leukemia entered a prospective study in which induction therapy with ATRA immediately was followed by a single course of mitoxantrone plus high-dose cytarabine (3 g/m2 every 12 hours, days 1-4), with no further treatment. Complete remission was achieved in 31 patients (81.6%) after a median time of 49 days of ATRA (to which chemotherapy was added at entry in 10 patients with leukocytosis). Thirty patients received the planned consolidation course. After a median follow-up of 36 months, four of these patients have relapsed and 24 are still in first complete remission, for an estimated disease-free survival of 75% at 60 months. The authors conclude that this single course consolidation of ATRA-induced remission provides excellent long-term control of acute promyelocytic leukemia.

Paracoccidioidomycosis in children in the state of Rio de Janeiro (Brazil). Geographic distribution and the study of a "reservarea".

Thirty six cases of acute disseminated paracoccidioidomycosis in 3 to 12 year-old children, natives of the state of Rio de Janeiro, were seen in the period 1981-1996. All patients were residents in the rural region of 15 counties, scattered on the Southwestern part of this state. The rural region of two neighboring counties, where 16 cases (44.4%) occurred, was visited. It exhibited the environmental conditions that are considered favorable to the survival of P. brasiliensis. The most important of these conditions, abundant watercourses and autochthonous forest, are distributed on well defined and limited areas, in which the dwellings are also localized. Probably, a careful epidemiological study of forthcoming cases of the disease in children may facilitate the search for the micro-niche of the fungus.

Granulocyte-macrophage colony-stimulating factor in post-remission therapy of acute myeloid leukemia.

The impact on occult leukemia of GM-CSF as a sensitizing agent has not been studied. We treated 41 adult patients with de novo acute myeloid leukemia, 25 of whom achieved complete remission and were given 1 to 3 post-remission courses, each course including GM-CSF begun 4 days prior to chemotherapy and given until day 3. After a median follow-up of 32 months, the probability of remaining in continuous complete remission was 17% at 46 months. GM-CSF in this setting was not associated with an improved outcome, arguing against a priming effect.

American cutaneous leishmaniasis associated with HIV infection: report of four cases.

OBJECTIVE: A report of four cases of American cutaneous leishmaniasis associated with HIV infection is presented. BACKGROUND: The association of mucocutaneous leishmaniasis and HIV infection is rare. Only 15 cases have been reported in the literature thus far. SUBJECTS: Four new cases are described and the differences between the clinical presentation in immunocompromised and immunocompetent patients are emphasized. CONCLUSIONS: Multiple cutaneous lesions plus mucosal involvement characterize the clinical presentation of American cutaneous leishmaniasis in association with HIV infection in the majority of the cases. A serological investigation for HIV infection is recommended for patients presenting with this type of clinical picture, especially if the patient is a young male.

Paracoccidioidomycosis in children in the state of Rio de Janeiro (Brazil): geographic distribution and the study of a "reservarea"

No periodo 1981-1996 foram observados 36 casos de paracoccidioidomicose aguda disseminada em criancas, entre 3 e 12 anos de idade, nativas do estado do Rio de Janeiro. Todos os pacientes residiam em regiäo rural, distribuida por 15 municipios localizados na parte sudoeste do estado. Dois municipios vizinhos, onde haviam ocorrido 16 (44,4 por cento) dos casos, foram visitados. Na regiäo rural de ambos, existem as condicöes climáticas e ambientais favoraveis a sobrevivência do P. brasiliensis. Dentre essas condicöes, as mais importantes, abundantes cursos de agua e vegetacao nativa, distribuem-se em areas limitadas e bem definidas. Nessas areas localizam-se, também, as casas dos ruriculas. Provavelmente, um cuidadoso estudo epidemiologico de novos casos, que venham a ocorrer na regiäo, facilitara a busca do nicho do fungom

Coccidioidomicose pulmonar aguda: primeiro surto epidêmico descrito no Ceará - segundo no Brasil / Acute pulmonar coccidioidomycosis: first epidemic outbreak in Ceara - second in Brazil

Os autores descrevem um surto de coccidioidomicose aguda em caçadores de tatu em Aiuaba, Cear . Revisam a literatura brasileira sobre esta micose. Verificam que todos os casos säo oriundos da regiÝo Nordeste. Apontam caçadores de tatu como grupo de risco. Alertam para a inclusäo do Brasil entre os países endêmicos e para a consideraçäo da doença no diagnóstico diferencial das pneumonias na prática médica. Destacam a importância da realizaçäo de inquéritos epidemiológicos para definir a situaçäo da coccidioidomicose no país.

Clinical and laboratorial correlation of postoperative hypocalcemia after extensive thyroidectomy.

The medical records of 84 patients submitted to extensive thyroidectomy from January 1991 to April 1995 were reviewed and the data was analyzed in order to verify a correlation between postoperative laboratories results and physical findings suggestive of hypocalcemia. It was verified that there was hypocalcemia in 51.2 percent of the patients, of which only 18.6 percent presented symptoms. It was concluded that asymptomatic hypocalcemia is frequent in extensive thyroidectomy and a routine screening for serum calcium in the postoperative period following thyroidectomy and calcium reposition must be systematic.

Clinical epidemiological study of 171 cases of cryptococcosis.

We retrospectively studied 171 patients with cryptococcosis who were divided into three groups according to their associated predisposing conditions (if any): group 1 comprised nonimmunosuppressed patients, group 2 comprised patients with AIDS, and group 3 comprised those patients with other conditions and/or who were users of immunosuppressive drugs. Analysis and correlation of the behavior of the mycosis among the three groups showed differences in the demographic data, clinical forms and manifestations of cryptococcosis, laboratory results, morbidity and mortality rates, and histopathologic aspects. Study of the clinical isolates of Cryptococcus neoformans from 83 patients with cryptococcosis showed that 75 were characterized as C. neoformans variety neoformans and eight as C. neoformans var. gatti. Comparison of the distribution of the gattii and neoformans varieties between the nonimmunosuppressed (group 1) and immunosuppressed (groups 2 and 3) patients showed a significant statistical difference (P < .01).

[Hemoptysis and the adult respiratory distress syndrome as the causes of death in leptospirosis. Changes in the clinical and anatomicopathological patterns]. / Hemoptise/s e síndrome de angústia respiratória do adulto como causas de morte na leptospirose. Mudanças de padrões clínicos e anatomopatológicos.

Human leptospirosis, one of the main urban endemics/epidemics in Brazil, has dramatically grown in the last three decades, especially after floods caused by summer rains. This presentation describes recent changes in the clinical patterns of this pathology in our region, expressed by the emergence of massive haemoptysis and acute respiratory distress syndrome, or both conditions associated. The evident changes in the respiratory structures emerged as a serious life threat and death mechanisms, becoming the main cause of death in leptospirosis among us because of their high incidence. This new face of the disease demands a revision of current concepts about its seriousness and raises speculations about the pathogenesis of such alterations.

Cryptococcus neoformans varieties as agents of cryptococcosis in Brazil.

The study of the clinical isolates of Cryptococcus neoformans from 83 Brazilian patients with disseminated cryptococcosis showed that 75 were C. neoformans var. neoformans and 8 were var. gattii. Twenty-seven isolates were serotyped; all 19 var. neoformans were serotype A and all 8 var. gattii were serotype B. The correlation of the varieties of C. neoformans with the presence or not of hosts predisposing conditions to the mycosis showed that: (1) cryptococcosis caused by gattii variety occurred in 7 (58.3%) of the 12 nonimmunosuppressed patients, and (2) cryptococcosis caused by neoformans variety occurred in 65 (98.5%) of the 66 AIDS patients and in all 5 patients with other immunosuppressive conditions. The comparison of the distribution of the gattii and neoformans varieties between the nonimmunosuppressed and immunosuppressed patients showed a significant statistical difference (p < 0.01).

PIP: 8 mycologists reviewed the medical records of 83 patients with disseminated crypttococcosis living in Brazil to examine the varieties of Cryptococcus neoformans. 12 patients were not immunosuppressed (group 1). 65 patients had AIDS (group 2). 5 patients either also had another disease and/or used immunosuppressive drugs (group 3). Almost all the clinical isolates were from the cerebrospinal fluid and/or blood (80 isolates [96.4%]. C. neoformans var. gattii caused cryotococcosis in 58.3% (7) of the nonimmunosuppressed patients. C. neoformans var. neoformans was responsible for crypttococcosis in all but 1 of the AIDS patients (98.5%) and in all 5 patients who had another disease and/or used immunosuppressive drugs. 6 of the 8 cases with crypttococcosis caused by C. neoformans var. gatti lived in rural areas during their first 10 years. A statistically significant difference existed between the nonimmunosuppressed group (group 1) and the immunosuppressed patients (groups 2 and 3) in the comparison of the distribution of the gattii and neoformans varieties (p.01). The omnipresence of C. neoformans var. neoformans, the urban population's regular exposure to C. neoformans var. neoformans, and predisposing conditions (i.e., immunosuppression) to crypttococcosis likely accounted for the neoformans variety mainly being the cause of crypttococcosis in areas in Brazil where C. neoformans var. gattii is indigenous.

[Internuclear ophthalmoplegia: initial and isolated clinical findings in bacterial endocarditis]. / Oftalmoplegia internuclear: achado clínico inicial e único em endocardite bacteriana.

Unilateral internuclear ophthalmoplegia become manifest by homolateral paralysis of ocular adduction and contralateral nystagmus. Principal causes are multiple sclerosis and vertebro-basilar insufficiency. We report a case in which this signal appeared as the first clinical manifestation of bacterial endocarditis and turned up to be the only neurological finding.