Bilateral adrenal histoplasmosis in an immunocompetent man

Histoplasmosis is a fungal disease that is endemic in Brazil. It may present as chronic pulmonary infection or in disseminated form. Disseminated histoplasmosis frequently affects the adrenal gland; however, unilateral involvement in immunosuppressed patients is the usual presentation. We report a case of an elderly immunocompetent male with history of weight loss, fever and bilateral adrenal mass who was successfully treated with itraconazole.

Doença meningocócica: comparação entre formas clínicas

Visando avaliar formas clínicas da doença meningocócica, foram revistos 201 casos diagnosticados como doença meningocócica, em Hospital Universitário da Universidade Federal Fluminense; durante o período de 1971 a 1996, dos quais 185 preencheram os critérios de inclusão. A caracterização clínico-laboratorial permitiu reagrupá-los nas formas de doença meningocócica com meningite, 18%, meningite e septicemia, 62%, e septicemia, 20%. Dados epidemiológicos disponíveis não diferenciaram formas clínicas. Na meningite meningocócica foi significativamente maior: tempo de história clínica; freqüência de manifestações neurológicas; e positividade da bacterioscopia, cultura e teste do látex no líquor. Na septicemia menigocócica, houve predomínio significativamente de: choque; letalidade e níveis maiores de tempo parcial de tromboplastina. Septicemia meningogócica e septicemia com meningite se diferenciaram da meningite meningocócica quanto a: tempo de história clínica; ocorrência de sinais neurológicos focais; coagulação intravascular disseminada e artrite. Dados clínico-laboratoriais levam a admitir meningite como forma localizada de doença meningocócica, e septicemia com meningite e septicemia como variações de gravidade da forma sistêmica da doença.

Transcriptional regulation of the mannosyltransferase-encoding gene pigm in inherited glycosylphosphatidylinositol (GPI) deficiency

RESUMO:O glicosilfosfatidilinositol (GPI) é um complexo glicolipídico utlizado por dezenas de proteínas, o qual medeia a sua ancoragem à superfície da célula. Proteínas de superfície celular ancoradas a GPI apresentam várias funções essenciais para a manutenção celular. A deficiência na síntese de GPI é o que caracteriza principalmente a deficiência hereditária em GPI, um grupo de doenças autossómicas raras que resultam de mutações nos genes PIGA, PIGL, PIGM, PIGV, PIGN, PIGO e PIGT, os quais sao indispensáveis para a biossíntese do GPI. Uma mutação pontual no motivo rico em GC -270 no promotor de PIGM impede a ligação do factor de transcrição (FT) Sp1 à sua sequência de reconhecimento, impondo a compactação da cromatina, associada à hipoacetilação de histonas, e consequentemente, impedindo a transcrição de PIGM. Desta forma, a adição da primeira manose ao GPI é comprometida, a síntese de GPI diminui assim como as proteínas ligadas a GPI à superficie das células. Pacientes com Deficiência Hereditária em GPI-associada a PIGM apresentam trombose e epilesia, e ausência de hemólise intravascular e anemia, sendo que estas duas últimas características definem a Hemoglobinúria Paroxística Nocturna (HPN), uma doença rara causada por mutações no gene PIGA. Embora a mutação que causa IGD seja constitutiva e esteja presente em todos os tecidos, o grau de deficiência em GPI varia entre células do mesmo tecido e entre células de tecidos diferentes. Por exemplo nos granulócitos e linfócitos B a deficiência em GPI é muito acentuada mas nos linfócitos T, fibroblastos, plaquetas e eritrócitos é aproximadamente normal, daí a ausência de hemólise intravascular. Os eventos transcricionais que estão na base da expressão diferencial da âncora GPI nas células hematopoiéticas são desconhecidos e constituem o objectivo geral desta tese. Em primeiro lugar, os resultados demonstraram que os níveis de PIGM mRNA variam entre células primárias hematopoiéticas normais. Adicionalmente, a configuração dos nucleossomas no promotor de PIGM é mais compacta em células B do que em células eritróides e tal está correlacionado com os níveis de expressão de PIGM, isto é, inferior nas células B. A presença de vários motivos de ligação para o FT específico da linhagem megacariocítica-eritróide GATA-1 no promotor de PIGM sugeriu que GATA-1 desempenha um papel regulador na sua transcrição. Os resultados mostraram que muito possivelmente GATA-1 desempenha um papel repressor em vez de activador da expressão de PIGM. Resultados preliminares sugerem que KLF1, um factor de transcrição restritamente eritróide, regula a transcrição de PIGM independentemente do motivo -270GC. Em segundo lugar, a investigação do papel dos FTs Sp demonstrou que Sp1 medeia directamente a transcrição de PIGM em ambas as células B e eritróide. Curiosamente, ao contrário do que acontece nas células B, em que a transcrição de PIGM requer a ligação do FT geral Sp1 ao motivo -270GC, nas células eritróides Sp1 regula a transcrição de PIGM ao ligar-se a montante e não ao motivo -270GC. Para além disso, demonstrou-se que Sp2 não é um regulador directo da transcrição de PIGM quer nas células B quer nas células eritróides. Estes resultados explicam a ausência de hemólise intravascular nos doentes com IGD associada a PIGM, uma das principais características que define a HPN. Por último, resultados preliminares mostraram que a repressão da transcrição de PIGM devida à mutação patogénica -270C>G está associada com a diminuição da frequência de interacções genómicas em cis entre PIGM e os seus genes “vizinhos”, sugerindo adicionalmente que a regulação de PIGM e desses genes é partilhada. No seu conjunto, os resultados apresentados nesta tese contribuem para o conhecimento do controlo transcricional de um gene housekeeping, específico-detecido, por meio de FTs genéricos e específicos de linhagem.-------------ABSTRACTC: Glycosylphosphatidylinositol (GPI) is a complex glycolipid used by dozens of proteins for cell surface anchoring. GPI-anchored proteins have various functions that are essential for the cellular maintenance. Defective GPI biosynthesis is the hallmark of inherited GPI deficiency (IGD), a group of rare autosomal diseases caused by mutations in PIGA, PIGL, PIGM, PIGV, PIGN, PIGO and PIGT, all genes indispensable for GPI biosynthesis. A point mutation in the -270GC-rich box in the core promoter of PIGM disrupts binding of the transcription factor (TF) Sp1 to it, imposing nucleosome compaction associated with histone hypoacetylation, thus abrogating transcription of PIGM. As a consequence of PIGM transcriptional repression, addition of the first mannose residue onto the GPI core and thus GPI production are impaired; and expression of GPI-anchored proteins on the surface of cells is severely impaired. Patients with PIGM-associated IGD suffer from life-threatening thrombosis and epilepsy but not intravascular haemolysis and anaemia, two defining features of paroxysmal nocturnal haemoglobinuria (PNH), a rare disease caused by somatic mutations in PIGA. Although the disease-causing mutation in IGD is constitutional and present in all tissues, the degree of GPI deficiency is variable and differs between cells of the same and of different tissues. Accordingly, GPI deficiency is severe in granulocytes and B cells but mild in T cells, fibroblasts, platelets and erythrocytes, hence the lack of intravascular haemolysis.The transcriptional events underlying differential expression of GPI in the haematopoietic cells of PIG-M-associated IGD are not known and constitute the general aim of this thesis. Firstly, I found that PIGM mRNA levels are variable amongst normal primary haematopoietic cells. In addition, the nucleosome configuration in the promoter of PIGM is more compacted in B cells than in erythroid cells and this correlated with the levels of PIGM mRNA expression, i.e., lower in B cells. The presence of several binding sites for GATA-1, a mega-erythroid lineage-specific transcription factor (TF), at the PIGM promoter suggested that GATA-1 has a role on PIGM transcription. My results showed that GATA-1 in erythroid cells is most likely a repressor rather than an activator of PIGM expression. Preliminary data suggested that KLF1, an erythroid-specific TF, regulates PIGM transcription but independently of the -270GC motif. Secondly, investigation of the role of the Sp TFs showed that Sp1 directly mediates PIGM transcriptional regulation in both B and erythroid cells. However, unlike in B cells in which active PIGM transcription requires binding of the generic TF Sp1 to the -270GC-rich box, in erythroid cells, Sp1 regulates PIGM transcription by binding upstream of but not to the -270GC-rich motif. Additionally, I showed that Sp2 is not a direct regulator of PIGM transcription in B and erythroid cells. These findings explain lack of intravascular haemolysis in PIGM-associated IGD, a defining feature of PNH. Lastly, preliminary work shows that transcriptional repression of PIG-M by the pathogenic -270C>G mutation is associated with reduced frequency of in cis genomic interactions between PIGM and its neighbouring genes, suggesting a shared regulatory link between these genes and PIGM. Altogether, the results presented in this thesis provide novel insights into tissuespecific transcriptional control of a housekeeping gene by lineage-specific and generic TFs.

Poisoning due to Philodryas olfersii (Lichtenstein, 1823) attended at Restauração Hospital in Recife, State of Pernambuco, Brazil: case report

Few papers have been published on snake bites caused by Philodryas olfersii. We report here the first case identified at the Centro de Assistência Toxicológica do Hospital da Restauração, Recife, State of Pernambuco. This case was described based on medical protocols, interviewing the patient and identifying the animal that caused the bite. The patient presented pain, heat, erythema, edema and ecchymosis, without other laboratory abnormalities or coagulation disorders. The treatment consisted of administration of eight ampoules of antibothropic serum, and post-administration allergenic reactions were observed. The importance of bites by opistoglyph snakes needs to be reconsidered in research and at specialized treatment centers.

Sistema de deteção de eventos adversos baseado num data warehouse

RESUMO - A Segurança do Doente tem assumido uma relevância crescente nas organizações de saúde, resultado da divulgação de diversos estudos que revelaram a magnitude deste problema e simultaneamente, de uma maior pressão por parte da opinião pública e da comunicação social. Este estudo pretende desenvolver e avaliar a performance de um sistema eletrónico de deteção de eventos adversos, baseado num Data Warehouse, por comparação com os resultados obtidos pela metodologia tradicional de revisão dos registos clínicos. O objetivo principal do trabalho consistiu em identificar um conjunto de triggers / indicadores de alerta que permitam detetar potenciais eventos adversos mais comuns. O sistema desenvolvido apresentou um Valor Preditivo Positivo de 18.2%, uma sensibilidade de 65.1% e uma especificidade de 68.6%, sendo constituído por nove indicadores baseados em informação clínica e 445 códigos do ICD-9-CM, relativos a diagnósticos e procedimentos. Apesar de terem algumas limitações, os sistemas eletrónicos de deteção de eventos adversos apresentam inúmeras potencialidades, nomeadamente a utilização em tempo real e em complemento a metodologias já existentes. Considerando a importância da problemática em análise e a necessidade de aprofundar os resultados obtidos neste trabalho de projeto, seria relevante a sua extensão a um universo mais alargado de instituições hospitalares, estando a sua replicabilidade facilitada, uma vez que o Data Warehouse tem por base um conjunto de aplicações disseminadas a nível nacional. O desenvolvimento e a consolidação dos sistemas eletrónicos de deteção de eventos adversos constitui inegavelmente uma área de futuro, com reflexos ao nível da melhoria da informação existente nas organizações e que contribuirá decisivamente para a melhoria dos cuidados de saúde prestados aos doentes.

Bits, Atoms, and Information Sharing: new opportunities for participation

The particular characteristics and affordances of technologies play a significant role in human experience by defining the realm of possibilities available to individuals and societies. Some technological configurations, such as the Internet, facilitate peer-to-peer communication and participatory behaviors. Others, like television broadcasting, tend to encourage centralization of creative processes and unidirectional communication. In other instances still, the affordances of technologies can be further constrained by social practices. That is the case, for example, of radio which, although technically allowing peer-to-peer communication, has effectively been converted into a broadcast medium through the legislation of the airwaves. How technologies acquire particular properties, meanings and uses, and who is involved in those decisions are the broader questions explored here. Although a long line of thought maintains that technologies evolve according to the logic of scientific rationality, recent studies demonstrated that technologies are, in fact, primarily shaped by social forces in specific historical contexts. In this view, adopted here, there is no one best way to design a technological artifact or system; the selection between alternative designs—which determine the affordances of each technology—is made by social actors according to their particular values, assumptions and goals. Thus, the arrangement of technical elements in any technological artifact is configured to conform to the views and interests of those involved in its development. Understanding how technologies assume particular shapes, who is involved in these decisions and how, in turn, they propitiate particular behaviors and modes of organization but not others, requires understanding the contexts in which they are developed. It is argued here that, throughout the last century, two distinct approaches to the development and dissemination of technologies have coexisted. In each of these models, based on fundamentally different ethoi, technologies are developed through different processes and by different participants—and therefore tend to assume different shapes and offer different possibilities. In the first of these approaches, the dominant model in Western societies, technologies are typically developed by firms, manufactured in large factories, and subsequently disseminated to the rest of the population for consumption. In this centralized model, the role of users is limited to selecting from the alternatives presented by professional producers. Thus, according to this approach, the technologies that are now so deeply woven into human experience, are primarily shaped by a relatively small number of producers. In recent years, however, a group of three interconnected interest groups—the makers, hackerspaces, and open source hardware communities—have increasingly challenged this dominant model by enacting an alternative approach in which technologies are both individually transformed and collectively shaped. Through a in-depth analysis of these phenomena, their practices and ethos, it is argued here that the distributed approach practiced by these communities offers a practical path towards a democratization of the technosphere by: 1) demystifying technologies, 2) providing the public with the tools and knowledge necessary to understand and shape technologies, and 3) encouraging citizen participation in the development of technologies.

Oropharyngeal histoplasmosis: report of eleven cases and review of the literature

INTRODUCTION: Histoplasmosis is a systemic mycosis endemic in Brazil, especially in the State of Rio Grande do Sul, where Histoplasma capsulatum was isolated from the soil. H. capsulatum may compromise unusual areas, including the oropharynx, particularly in patients presenting disseminated histoplasmosis; which is associated with a state of immunosuppression, such as AIDS. METHODS: During database analysis of a total of 265 cases of histoplasmosis, the medical records of 11 patients with histological or microbiological diagnoses of oral histoplasmosis (OH) between 1987 and 2008 were retrospectively reviewed. RESULTS: This work reports 11 cases of OH, the majority presenting histopathological or microbiological evidence of disseminated histoplasmosis (DH). In the patients with DH, OH was the first manifestation of histoplasmosis. Five of the 11 patients discussed were HIV-seropositive with clinical and laboratory findings of AIDS. Four patients presented active pulmonary tuberculosis concomitant with histoplasmosis. Treatment was based on the use of itraconazole and amphotericin B deoxycholate. Eight patients responded successfully to therapy after one year, two did not come back for reevaluation and one died despite adequate therapy. CONCLUSIONS: Oral histoplasmosis is closely associated with immunosuppression status, especially in patients presenting AIDS; moreover, in many cases, OH is the first sign of disseminated histoplasmosis.

Occurrence and risk factors associated with infection by Toxoplasma gondii in goats in the State of Alagoas, Brazil

INTRODUCTION: Goats are considered very susceptible to infection by Toxoplasma gondii and when this occurs during pregnancy, it may cause fetal death with subsequent fetal resorption, abortion, mummification, stillborn or the birth of weak goats. The objective of this work was to determine the occurrence of and identify risk factors for T. gondii infection in goats in different mesoregions in the State of Alagoas. METHODS: The research was conducted on 24 goat breeding farms in 10 municipalities. A total of 454 blood samples were examined for anti-T. gondii antibodies by indirect immunofluorescence antibody test. To evaluate the risk factors of toxoplasmosis in goats, questionnaires were applied analyzing the farm's production system and nutritional, reproductive and sanitary management. RESULTS: Disease occurrence was 39% with 95.8% of farms presenting seropositive animals. Significant associations were observed for mesoregion (OR = 0.23; 95%CI = 0.09 - 0.57), age (OR = 0.36; 95%CI = 0.20 - 0.64), semi-intensive herd management (OR = 8.70; 95%CI = 1.87 - 40.43), access of cats to water provided for goats (OR = 3.38; 95%CI = 1.89-6.02) and cats feeding on placental remnants (OR = 2.73; 95%CI = 1.38 - 5.40). CONCLUSIONS: Toxoplasma gondii infection is disseminated in the State of Alagoas and the adoption of a program that monitors infection foci is required to reduce the risk factors identified in the present study.

Bacillary angiomatosis in HIV-positive patient from Northeastern Brazil: a case report

It is a report of disseminated bacillary angiomatosis (BA) in a 23-year-old female patient, who is HIV-positive and with fever, weight loss, hepatomegaly, ascites, and papular-nodular skin lesions. The clinical and diagnostic aspects involved in the case were discussed. Bacillary angiomatosis must always be considered in the diagnosis of febrile cutaneous manifestations in AIDS.

Acute meningoencephalomyelitis due to varicella-zoster virus in an AIDS patient: report of a case and review of the literature

Varicella-zoster virus (VZV) meningoencephalomyelitis is a rare but severe neurological complication of VZV reactivation in immunocompromised patients. We report the case of an HIV-infected individual who developed an acute and severe meningoencephalomyelitis accompanied by a disseminated cutaneous eruption due to VZV. The presence of VZV DNA in cerebrospinal fluid was confirmed by polymerase chain reaction (PCR) technique. The patient started undergoing an intravenous acyclovir therapy with a mild recovery of neurological manifestations. Varicella-zoster virus should be included as a cause of acute meningoencephalomyelitis in patients with AIDS. Early diagnosis followed by specific therapy should modify the rapid and fulminant course for this kind of patients.

Liver transplantation for neotropical polycystic echinococcosis caused by Echinococcus vogeli: a case report

Neotropical polycystic echinococcosis (NPE) is a parasitic disease caused by cestodes of Echinococcus vogeli. This parasite grows most commonly in the liver, where it produces multiples cysts that cause hepatic and vessel necrosis, infects the biliary ducts, and disseminates into the peritoneal cavity, spreading to other abdominal and thoracic organs. In cases of disseminated disease in the liver and involvement of biliary ducts or portal system, liver transplantation may be a favorable option. We present a report of the first case of liver transplantation for the treatment of advanced liver NPE caused by E. vogeli.

Involvement and interactions of different immune cells and their cytokines in human visceral leishmaniasis

Visceral leishmaniasis (VL) or kala-azar, a disseminated infection of the lymphoreticular system of the body, is marked by severe defect in immune system of the host. Successful cure of VL depends on the immune status of the host in combination with the effects of the antileishmanial drugs. The rationale approach towards eradication of this disease would be to potentiate the immune functioning of the host in addition to parasite killing. This review deals with different aspects of adaptive and innate immune responses and explores their role in protection or pathogenesis of VL. IL-10 has emerged as the principal cytokine responsible for disease pathogenesis, although evidences regarding its source during active VL remain inconclusive. On the other hand, IFNγ, under the influence of IL-12, is mostly correlated with healing of the disease. Chemokines are important in mounting cell-mediated immune response as they can prevent parasite invasion in association with cytokines. Different types of T cells like CD4, CD8 and NK T cells also contribute to the immunology of this disease. In spite of conflicting reports, the role of regulatory T cells in VL pathogenesis is important. Recently discovered Th17 subset and its different members have been reported to perform diverse functions in the course of VL and leishmaniasis as a whole. Innate immune responses, depending on the cell types, are essential in early parasite detection and subsequent development of an efficient NK cell response. Immunotherapy targeting IL-10 could be looked upon as an interesting option for the treatment of VL.

Histoplasmosis in immunocompetent individuals living in an endemic area in the Brazilian Southeast

Introduction The distribution of infection by Histoplasma capsulatum in Brazil is heterogeneous, and the number of cases affecting immunocompetent individuals is relatively small. This study reports the epidemiological and clinical data regarding histoplasmosis in non-immunosuppressed individuals. Methods The study included only the immunocompetent patients with histoplasmosis who were diagnosed between 1970 and 2012 at a university hospital located in Ribeirão Preto, State of São Paulo, Brazil. Clinical and epidemiological data were collected retrospectively from the patient records. Results Of the 123 patients analyzed, 95 had an active disease that manifested in the different clinical forms of histoplasmosis. Men were the predominant gender, and most patients resided in the Northeast of the State of São Paulo and in the nearby municipalities of the State of Minas Gerais. The risk factors for acquiring histoplasmosis and prolonged contact in a rural environment were recorded in 43.9% and 82.9% of cases, respectively. Smoking, alcoholism, and comorbidity rates were high among the patients with the chronic pulmonary and subacute/chronic disseminated forms of histoplasmosis. Many patients achieved clinical cure spontaneously, but 58.9% required antifungals; the disease lethality rate was 5.3%. Conclusions Immunocompetent individuals manifested the diverse clinical forms of histoplasmosis over a period of 4 decades, revealing an additional endemic area of this fungal disease in the Brazilian Southeast.

CD8+ T cells in situ in different clinical forms of human cutaneous leishmaniasis

Introduction Leishmania braziliensis infection induces a large spectrum of lesions that clinically manifest as nodules or papules that progress to ulcers. Although it is already known that T helper cells predominate in the lesions, cytotoxic T cells have also been reported to be present, and their role in leishmaniasis immunopathogenesis is not well known. This study investigated the amounts of CD8+ and granzyme B+ cells in different clinical forms of human cutaneous leishmaniasis (CL). Methods Forty tissue fragments from early (E-CL) and late CL (L-CL) lesions and from disseminated leishmaniasis (DL) - papules and ulcers - were characterized. The inflamed area per fragment was calculated, and the CD8 and granzyme B expression levels in the infiltrates were quantified by counting positive cells in 15 fields. The localization of CD8 and granzyme B was graded subjectively. Results Inflammation was higher in L-CL and DL ulcers. CD8 expression was increased in late ulcerated lesions compared to recent lesions. The increase in CD8+ cells also correlated with the duration of the lesion. Papules had a higher frequency of granzyme B+ cells than E-CL lesions, although the frequency was similar to those for late and DL ulcers. CD8+ cells were mostly found in the papillary dermis. Conclusions CD8+ T and granzyme B+ cells are present in the inflammatory infiltrates of CL and DL and may participate in the immunopathogenesis of Leishmania infection.

Invasive aspergillosis in a user of inhaled cocaine: rhinosinusitis with bone and cartilage destruction

Aspergillosis is an infection caused by saprophytic fungi of the genus Aspergillus, which typically occurs in immunosuppressed individuals, but has also been reported in immunocompetent patients. The main routes of entry are the respiratory tract, skin, cornea, and ear, and the infection may be localized or disseminated by contiguity or vascular invasion. We report a severe case of rhinosinusitis with cutaneous involvement, caused by invasive aspergillosis, in an immunocompetent user of inhaled cocaine. Invasive aspergillosis related to cocaine abuse has not yet been reported in the literature. After itraconazole treatment and surgical debridement, complete clinical remission was achieved. Nasal reconstruction with a skin graft over a silicone prosthesis resulted in a satisfactory esthetic outcome.