IGRT com CBCT: o impacto na precisão em radioterapia

Mestrado em Radiações Aplicadas às Tecnologias da Saúde.

Dosimetric effect of tissue heterogeneity for 125I prostate implants

Aim - To use Monte Carlo (MC) together with voxel phantoms to analyze the tissue heterogeneity effect in the dose distributions and equivalent uniform dose (EUD) for (125)I prostate implants. Background - Dose distribution calculations in low dose-rate brachytherapy are based on the dose deposition around a single source in a water phantom. This formalism does not take into account tissue heterogeneities, interseed attenuation, or finite patient dimensions effects. Tissue composition is especially important due to the photoelectric effect. Materials and Methods - The computed tomographies (CT) of two patients with prostate cancer were used to create voxel phantoms for the MC simulations. An elemental composition and density were assigned to each structure. Densities of the prostate, vesicles, rectum and bladder were determined through the CT electronic densities of 100 patients. The same simulations were performed considering the same phantom as pure water. Results were compared via dose-volume histograms and EUD for the prostate and rectum. Results - The mean absorbed doses presented deviations of 3.3-4.0% for the prostate and of 2.3-4.9% for the rectum, when comparing calculations in water with calculations in the heterogeneous phantom. In the calculations in water, the prostate D 90 was overestimated by 2.8-3.9% and the rectum D 0.1cc resulted in dose differences of 6-8%. The EUD resulted in an overestimation of 3.5-3.7% for the prostate and of 7.7-8.3% for the rectum. Conclusions - The deposited dose was consistently overestimated for the simulation in water. In order to increase the accuracy in the determination of dose distributions, especially around the rectum, the introduction of the model-based algorithms is recommended.

Influence of attenuation correction in the MPI image reconstructed by the ‘Evolution for Cardiac’™

The acquisition of a Myocardial Perfusion image (MPI) is of great importance for the diagnosis of the coronary artery disease, since it allows to evaluate which areas of the heart aren’t being properly perfused, in rest and stress situations. This exam is greatly influenced by photon attenuation which creates image artifacts and affects quantification. The acquisition of a Computerized Tomography (CT) image makes it possible to get an atomic images which can be used to perform high-quality attenuation corrections of the radiopharmaceutical distribution, in the MPI image. Studies show that by using hybrid imaging to perform diagnosis of the coronary artery disease, there is an increase on the specificity when evaluating the perfusion of the right coronary artery (RCA). Using an iterative algorithm with a resolution recovery software for the reconstruction, which balances the image quality, the administered activity and the scanning time, we aim to evaluate the influence of attenuation correction on the MPI image and the outcome in perfusion quantification and imaging quality.

Avaliação de realce tardio do miocárdio por tomografia computorizada

A distinção entre miocárdio atordoado e danificado tem sido uma preocupação relevante, no cenário de um enfarte agudo do miocárdio (EAM). A avaliação da viabilidade do miocárdio, pós-enfarte, é de importância vital, no contexto clínico, principalmente numa fase inicial. Actualmente a Ressonância Magnética Cardíaca é o exame de referência para a avaliação de viabilidade do miocárdio. No entanto, é um exame com elevado custo e de difícil acesso. Estudos preliminares demonstraram potencial na utilização de imagens por Tomografia Computorizada para avaliação da área de enfarte, quer em estudos animais quer em humanos. É objectivo desta tese verificar a utilidade de um protocolo de avaliação de viabilidade do miocárdio, com base em imagens de realce tardio (RT) por Tomografia Computorizada, após um procedimento de intervenção coronária percutânea, no contexto de enfarte agudo do miocárdio com elevação do segmento ST (STEMI). Pretende-se igualmente contribuir para a análise da imagem médica do miocárdio, proporcionando métodos de quantificação do RT e software de suporte à decisão médica nesta modalidade de imagem substancialmente recente. São avaliados vários processos para a quantificação do volume de RT, incluindo um método inovador baseado na detecção automática do miocárdio normal. _E ainda proposto um algoritmo para detecção automática do grau de transmuralidade, por segmento do miocárdio, e comparado o seu grau de eficiência face ao diagnóstico médico dos mesmos exames. Apesar do reduzido número de exames utilizado para validação das técnicas descritas nesta tese, os resultados são bastante promissores e podem constituir uma mais-valia no auxilio à gestão do paciente com EAM.

Anemia de células falciformes na idade pediátrica : contribuição para o estudo das suas principais complicações e indicadores de prognóstico

RESMO: Introdução: A anemia de células falciformes doença hereditária, com repercussão multi-orgânica, tem grande variabilidade na sua expressão clínica. Daí o interesse do estudo de indicadores de prognóstico. A investigação realizada foi precedida de um resumo histórico incidindo sobre a compreensão de aspectos fundamentais da doença ao longo dos tempos. Na primeira parte do estudo e após revisão bibliográfica, foram referidos dados da fisiopatologia como base para os estudos que integram a presente dissertação. Abordou-se o estado da arte relativamente às complicações, aos indicadores de prognóstico e à terapêutica utilizada. Objectivos: Constituíram objectivos deste estudo realizado numa amostra populacional representativa: identificar as lesões a nível dos sistemas cardio-respiratório e nervoso central, avaliando-se as respectivas repercussões; avaliar a presença de indicadores de prognóstico entre as variáveis seleccionadas; estudar a eficácia e toxicidade da HU nos doentes com as formas graves da ACF. Para a prossecução destes objectivos foram delineados para além do estudo global três estudos específicos: Estudo 1- repercussão no sistema cardio-respiratório; Estudo 2- repercussão no sistema nervoso central; Estudo 3- terapêutica com hidroxiureia. Doentes e métodos: Procedeu-se a um estudo prospectivo e multi-institucional durante um período de três anos tendo-se seleccionado para a amostra, e de acordo com critérios pré-definidos, 30 doentes com ACF na fase estável da doença, com idades compreendidas entre os sete e os 18 anos, todos de origem africana à excepção de um caucasiano. O diagnóstico baseou-se em técnicas de electroforese e estudo molecular que definiu o genotipo da doença e a presença da delecção da -talassémia assim como os haplotipos da amostra populacional. Foram utilizadas diferentes metodologias para avaliar a existência de lesão pulmonar e cerebral. Através do estudo estatístico foram seleccionadas diversas variáveis como hipotéticos indicadores de prognóstico. Estudo 1. Para determinar a existência de lesão a nível pulmonar usaram-se duas metodologias diferentes, a avaliação da função pulmonar com estudo da saturação da Hb em O2 no sangue arterial e a tomografia computadorizada de alta resolução. Estudou-se também a possível disfunção cardíaca como repercussão da lesão pulmonar, através do ecocardiograma, e os indicadores de prognóstico com significado estatístico para a lesão encontrada. Estudo 2. O desenho deste estudo foi sobreponível ao anterior, mas com metodologia adequada para o SNC. Procedeu-se ao estudo das lesões cerebrais por meio de exames imagiológicos, (RMN-CE e DTC) e de testes psicológicos. Correlacionaram-se as três metodologias utilizadas e a importância de cada uma para a decisão de atitudes terapêuticas preventivas. Estudo 3. Consistiu num estudo aberto prospectivo não controlado com nove crianças e adolescentes com formas graves de ACF, com o objectivo de avaliar a eficácia da terapêutica com hidroxiureia, durante um período de 24 meses. Todos os doentes completaram no mínimo 15 meses de terapêutica, com uma dose final média de 194 mg/K/dia. Resultados globais: Durante o período anterior à investigação caracterizou-se a amostra populacional estudada quanto ao fenotipo genético, clínico e hematológico de acordo com os critérios utilizados por outros investigadores. Verificou-se: predomínio do haplotipo Bantu na forma homozigótica em 53% dos doentes; número total de EVO ≥3/ano em 87,5% dos doentes; crises de sequestração em 18,75%; dactilites no primeiro ano de vida em 31,2%; quadro de sépsis grave apenas num doente; crises de hiper-hemólise em 50%; e STA em 59,38% dos doentes. Quanto ao fenotipo hematológico evidenciaram-se como factores de risco reticulocitose (13,1x103/l) e hiperbilirrubinémia (2,5 mg/dl) e como factores de bom prognóstico a presença de delecção de um gene da -talassémia em 46,9% dos doentes e valor médio de Hb 8,1 g/dl. Resultados dos estudos parcelares: Estudo 1. Deste estudo infere-se que a DPR ligeira foi diagnosticada em 70% dos doentes, uma vez que as alterações da difusão não foram estatisticamente significativas, o estudo dos gases no sangue não evidenciaram resultados anormais e a TCAR evidenciou alterações em 43,3% dos doentes. Apenas num doente se verificou doença pulmonar obstrutiva relacionada com maior número da STA.O estudo da disfunção cardíaca encontrada em 86,7% dos doentes não reflecte a repercussão da DPR a nível cardíaco, podendo estar associada às alterações fisiopatológicas da própria anemia crónica. Encontraram-se indicadores de prognóstico hematológicos e clínicos. Entre os primeiros, valores de Hb ≥8,5 g/dl e de HbF ≥13% foram considerados indicadores de bom prognóstico para a lesão pulmonar. Em relação aos parâmetros clínicos, as STA não foram consideradas indicadoras de prognóstico para a DPR ao contrário do que se verificou com o número de EVO. Pela análise dos parâmetros genéticos e socio-económicos provou-se a ausência de relação estatisticamente significativa com lesão pulmonar. Estudo 2. Pela RMN-CE foram diagnosticados ES em 33,3% com uma localização preferencial na substância branca profunda em 26,6% dos doentes. Relativamente aos parâmetros hematológicos seleccionados, o valor médio da HbF 8,6% constituíu um indicador de bom prognóstico para o aparecimento de ES, enquanto o valor médio de leucócitos 12.39x103/μl foi considerado um indicador de mau prognóstico. No estudo do DTC apenas um doente apresentou aumento da velocidade do fluxo cerebral na ACM igual a 196 cm/segundos, associado a vasculopatia grave. Os testes psicológicos alterados em 80% dos doentes mostraram ser o método mais sensível para detectar alterações do neurodesenvolvimento, mas sem correlação com os ES em 10% dos doentes. Realça-se a baixa percentagem de DTC patológicos encontrados neste estudo em relação ao número elevado de ES e de testes psicológicos alterados, não se verificando concordância entre os três exames. Dos indicadores de prognóstico estudados a -talassémia foi considerada um factor de protecção para o coeficiente de inteligência da escala de Wechsler. Em relação a parâmetros clínicos estudados os doentes com maior número de EVO, tem em média valores inferiores nos testes psicológicos. Estudo 3. Neste estudo verificou-se que o valor médio da HbF aumentou significativamente de 7,0±4% para 13,7±5,3% (p=0,028) ao fim de 15 meses de terapêutica com hidroxiureia. Clinicamente todos os doentes responderam significativamente com uma redução de 80% no número de EVO, 69% no número de internamentos, 76% no número de dias de hospitalização e 67% no número de transfusões. Deste modo comprovou-se não só a eficácia desta terapêutica neste grupo pediátrico como também a falta de efeitos secundários significativos. Considera-se a necessidade de estudos mais prolongados e em grande séries, para com segurança se usar a HU antes que a lesão orgânica se estabeleça, portanto logo nos primeiros anos de vida. Conclusão: Na amostra populacional estudada foram evidenciadas lesões pulmonares e cerebrais na grande maioria dos doentes que condicionaram a sua qualidade de vida. Foram identificados indicadores de prognóstico que poderão eventualmente ditar medidas terapêuticas precoces com o objectivo de diminuir a morbilidade e a mortalidade neste grupo etário. Demonstrou-se que a terapêutica com a HU foi eficaz e bem tolerada----------ABSTRACT: Background: Sickle cell anemia (SCA), a hereditary disease characterized by pain and lifetime multi-organic lesion, is a challenge for all that work with carriers of this disease. The clinical expression variability of SCA is a constant reality and a problem to be solved in the current world of investigation, for which the knowledge of prognostic indicators responsible for the different aspects of clinical evolution diversity wiil be an added value. The study is preceded by a historical summary of the most important factors in the evolution of SCA, which are in themselves, an incentive for future research. In the first part of the study, after an extensive bibliographical revision, physiopathology data is referred to in general and specifically regarding the target organs, that constituted the base for the studies presented in the dissertation. The state of the art for the complications to be studied, the choice of prognostic indicators and the therapeutics application, were approached for the renewed interest in the theme. Aims: In regard to the investigation, the objective was to study the lesions in the most affected organs of a chosen pediatric group, to investigate prognostic indicators for lung and cerebral lesions and to evaluate the protective effect of hydroxyurea in children with severe outcomes. Patients and methods: A prospective and multi-institutional study was carried out during a three-year period, February 1998 to March 2001, with children and adolescents followed up at a Immunohematology Outpatient Clinic of Dona Estefânia's Hospital, Lisbon. Based in predefined criteria, 30 children with SCA were selected in a stable phase of the disease, aged from seven to 18 years old, all of whom were of African origin with exception of one who was Caucasian. The diagnosis was based on electrophoresis techniques and molecular study that allowed to define the genotype, the presence of deletional alpha-thalassemia as well as haplotypes in the population. Different methodologies were used to evaluate the existence of lung and cerebral lesion. Statistical study of the different variables selected the prognostic indicators. In Study 1, to determine the existence of lung lesion two different methodologies were used: pulmonar function study with arterial blood gases determination; and high resolution computerized tomography. Heart dysfunction as a repercussion of lung lesion was also studied through echocardiography, and prognostic indicators were statistically significant for lesions found. The design of Study 2 was similar to Study 1, but with the appropriate methodology for CNS. After neurological examination, which was normal in all patients (control group), cerebral lesions were studied with imagiologic exams (MRN-CE and TCD) and psychological tests. These three methodologies were correlated and the importance of each one in the decision of the therapeutic profilactic attitudes. Study 3 consisted of a controlled prospective open study in children with severe forms of SCA, with the aim of the evaluating therapeutic effectiveness of hydroxyurea, during a period of 24 months. Results: In the global overall study preceding the Studies 1,2 and 3, there were a prevalence of haplotype Bantu (53%) and other risk factors, namely the number of VOC (87,5%), sequestration crisis (18,75%), dactilytis in first year of life(31,2%), hyperhemolysis crisis (50%) and ATC in more than half of the patients (59,38%). This group of bad prognostic indicators, associated with the population of the lower class according to the Graffar scale, demonstrates the importance of primary health care services, information provided to the children and their relatives, as well as the interest in prophylactic therapeutics, specific screening and prenatal diagnosis. Study 1. It was evident from this study that slight RPD was diagnosed in 70% of the patients, because alterations of the diffusion had no statistical significance and arterial blood gases determinations were normal. Only one patient had restrictive lung disease related with numerous ACS. However ACS was not considered a prognostic indicator for RPD, contrary to the number of EVO. HRTC revealed discreet fibrotic lines that could be related with slight RPD, but the lack of correlation of these two exams (33%) supports the value of lung function tests for precocious diagnosis of RPD. Heart dysfunction was found in 86,7% of patients, does not reflect the repercussion of RPD, but with the physiopathology of chronic anemia. Hematologic and clinical prognostic indicators were found. Good prognostic indicators for the non-evolution of RPD with average Hb values of ≥ 8,5 g/dl and average HbF values of ≥13%, respectively. The genetic and social-economic factors had no statistical significance; nevertheless, they were more prevalent among Bantu haplotype (53,3%) in patients with RPD. Study 2. RMN-CE detected SI in 33,3% of the patients, with preferential location in deep white substance in 26,6% and in front lobe in 20%. This distribution can be related to structural aspects of the brain and with the high sensibility of this organ to hypoxia. From the hematological parameters selected, average HbF value 8,6% and average leucocyte count 12.39x103/μl were prognostic indicators with different meaning to SI. The increase in the total bilirubin related to hyperhemolysis clinically explains the genesis of SI In the TCD study, only one patient had increased cerebral flow speed >196 cm/sec in CMA, which corresponded to serious vasculopathy in AngioMR. This patient never present previously neurological symptoms and had several hyperhemolysis crisis and VOC as risk factors. Low percentage of pathological TCD in this study, in relation to the high number of SI and altered tests, although without correlation among the three exams, is probably attributed to factors related to the methodology, aspects of cerebral physiopathology or perhaps a sign of good prognostic if the duration of study had not been so short. TCD should be used as a screening method in the age groups with higher risk of AVC and should never be considered separately in prophylactic therapeutics indication. Psychological tests were the most sensitive method to detect neurodevelopment impairment; in 80% of patients the neuropsychologics tests were altered, but without correlation with SI (10%). Since SI can become evident during the first two years of life and develop with time, the first psychological tests should be carried out between 3 and 5 years of age to timely be referred to special education and stimulation programs. Prognostic indicators to psychological tests were also found: alpha-thalassemia was found to be a protection factor of the IQ, just as other hematologic factors (hematocrit, MGCV and erythrocytes count). In relation to clinical parameters, although without statistical significance, patients with larger number of VOC had average lower scores versus the average in tests, except in TP. Results from different studies were conclusive as to the type of lesion found and the importance of prognostic indicators. Study 3. All the patients completed a minimum of 15 months therapeutic treatment with the final average daily dose of 19±4 mg/kg/day. The average value of the fetal hemoglobin increased significantly from 7,0±3,9% to 13,7±5,3% (p=0.028). The HbF average values increased from 6% to 15% after 15 months of therapeutic treatment. Clinically there was a reduction of 80% in the number of VOE , 69% in the number of hospitalization, 76% in the number of days of hospitalization and 67% in the number of transfusions. Once again the effectiveness of this treatment in this pediatric group, as well as the lack of any significant secondary effects, was evident. The study confirms the need for further detailed research in order to safely effect the appropriate treatment prior to the development of organic lesions, which ideally should be in the first year of life. Conclusions: These results allow us to clarify the importance of either pulmonary lesions or either nervous central system impairment among patients, children and adolescents, with sickle cell anemia. These lesions were demonstrated in most of the patients studied compromising their quality of life and the mortality. The treatment with HU is proved to be effective and having low toxicity.

Coccidioidomycosis in Brazil. A case report

Coccidioidomycosis is an endemic infection with a relatively limited geographic distribution: Mexico, Guatemala, Honduras, Colombia, Venezuela, Bolivia, Paraguai, Argentina and the southwest of the United States. In these countries, the endemic area is restricted to the semiarid desert like regions which are similar to the northeast of Brazil. Case report: The patient is a 32 year-old male, born in the state of Bahia (Northeast of Brazil) and has been living in São Paulo (Southeast) for 6 years. He was admitted at Hospital das Clínicas, at the Department of Pneumology in October 1996, with a 6 month history of progressive and productive cough, fever, malaise, chills, loss of weight, weakness and arthralgia in the small joints. Chest x-rays and computerized tomography disclosed an interstitial reticulonodular infiltrate with a cavity in the right upper lobe. The standard potassium hydroxide preparation of sputum and broncoalveolar lavage demonstrated the characteristic thickened wall spherules in various stages of development. Sabouraud dextrose agar, at 25° C and 30° C showed growth of white and cottony aerial micelium. The microscopic morphology disclosed branched hyphae characterized by thick walled, barrel shaped arthroconidia alternated with empty cells. The sorological studies with positive double immunodiffusion test, and also positive complement fixation test in 1/128 dilution confirmed the diagnosis. The patient has been treated with ketoconazole and presents a favorable clinical and radiological evolution

Perinephric and renal abscesses in children: a study of three cases

Perinephric and renal abscesses are rare in childhood, but they must be remembered in the differential diagnosis of fever and abdominal or flank pain. This paper reports three cases whose solution was found after clinical and surgical treatment. The importance of ultrasound and computerized tomography (CT) in prompt diagnosis is highlighted in this work. The use of these methods along the improved antimicrobial therapy may result in decrease in mortality due to this pathology.

Cerebral aspergillosis due to Aspergillus fumigatus in AIDS patient: first culture - proven case reported in Brazil

Cerebral aspergillosis is a rare cause of brain expansive lesion in AIDS patients. We report the first culture-proven case of brain abscess due to Aspergillus fumigatus in a Brazilian AIDS patient. The patient, a 26 year-old male with human immunodeficiency virus (HIV) infection and history of pulmonary tuberculosis and cerebral toxoplasmosis, had fever, cough, dyspnea, and two episodes of seizures. The brain computerized tomography (CT) showed a bi-parietal and parasagittal hypodense lesion with peripheral enhancement, and significant mass effect. There was started anti-Toxoplasma treatment. Three weeks later, the patient presented mental confusion, and a new brain CT evidenced increase in the lesion. He underwent brain biopsy, draining 10 mL of purulent material. The direct mycological examination revealed septated and hyaline hyphae. There was started amphotericin B deoxycholate. The culture of the material demonstrated presence of the Aspergillus fumigatus. The following two months, the patient was submitted to three surgeries, with insertion of drainage catheter and administration of amphotericin B intralesional. Three months after hospital admission, his neurological condition suffered discrete changes. However, he died due to intrahospital pneumonia. Brain abscess caused by Aspergillus fumigatus must be considered in the differential diagnosis of the brain expansive lesions in AIDS patients in Brazil.

Reconstrução de Superfícies usando um Scanner 3D de Luz Estruturada

Ao longo dos últimos anos, os scanners 3D têm tido uma utilização crescente nas mais variadas áreas. Desde a Medicina à Arqueologia, passando pelos vários tipos de indústria, ´e possível identificar aplicações destes sistemas. Essa crescente utilização deve-se, entre vários factores, ao aumento dos recursos computacionais, à simplicidade e `a diversidade das técnicas existentes, e `as vantagens dos scanners 3D comparativamente com outros sistemas. Estas vantagens são evidentes em áreas como a Medicina Forense, onde a fotografia, tradicionalmente utilizada para documentar objectos e provas, reduz a informação adquirida a duas dimensões. Apesar das vantagens associadas aos scanners 3D, um factor negativo é o preço elevado. No âmbito deste trabalho pretendeu-se desenvolver um scanner 3D de luz estruturada económico e eficaz, e um conjunto de algoritmos para o controlo do scanner, para a reconstrução de superfícies de estruturas analisadas, e para a validação dos resultados obtidos. O scanner 3D implementado ´e constituído por uma câmara e por um projector de vídeo ”off-the-shelf”, e por uma plataforma rotativa desenvolvida neste trabalho. A função da plataforma rotativa consiste em automatizar o scanner de modo a diminuir a interação dos utilizadores. Os algoritmos foram desenvolvidos recorrendo a pacotes de software open-source e a ferramentas gratuitas. O scanner 3D foi utilizado para adquirir informação 3D de um crânio, e o algoritmo para reconstrução de superfícies permitiu obter superfícies virtuais do crânio. Através do algoritmo de validação, as superfícies obtidas foram comparadas com uma superfície do mesmo crânio, obtida por tomografia computorizada (TC). O algoritmo de validação forneceu um mapa de distâncias entre regiões correspondentes nas duas superfícies, que permitiu quantificar a qualidade das superfícies obtidas. Com base no trabalho desenvolvido e nos resultados obtidos, é possível afirmar que foi criada uma base funcional para o varrimento de superfícies 3D de estruturas, apta para desenvolvimento futuro, mostrando que é possível obter alternativas aos métodos comerciais usando poucos recursos financeiros.

Oral cavity eumycetoma

Mycetoma is a pathological process in which eumycotic (fungal) or actinomycotic causative agents from exogenous source produce grains. It is a localized chronic and deforming infectious disease of subcutaneous tissue, skin and bones. We report the first case of eumycetoma of the oral cavity in world literature. CASE REPORT: A 43-year-old male patient, complaining of swelling and fistula in the hard palate. On examination, swelling of the anterior and middle hard palate, with fistula draining a dark liquid was observed. The panoramic radiograph showed extensive radiolucent area involving the region of teeth 21-26 and the computerized tomography showed communication with the nasal cavity, suggesting the diagnosis of periapical cyst. Surgery was performed to remove the lesion. Histopathological examination revealed purulent material with characteristic grain. Gram staining for bacteria was negative and Grocott-Gomori staining for the detection of fungi was positive, concluding the diagnosis of eumycetoma. The patient was treated with ketoconazole for nine months, and was considered cured at the end of treatment. CONCLUSION: Histopathological examination, using histochemical staining, and direct microscopic grains examination can provide the distinction between eumycetoma and actinomycetoma accurately.

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematodermic neoplasia with frequent cutaneous involvement and leukemic dissemination. We report the case of a 76-year-old man with a 2 month history of violaceous nodules and a tumor with stony consistency, located on the head, and mandibular, cervical and supraclavicular lymphadenopathies. Multiple thoracic and abdominal adenopathies were identified on computerized tomography. Flow cytometry analysis of the skin, lymph node and bone marrow biopsies demonstrated the presence of plasmocytoid dendritic cell neoplastic precursor cells (CD4+, CD45+, CD56+ and CD123+ phenotype). After initial clinical and laboratorial complete remission with chemotherapy, the patient died due to relapse of the disease associated with the appearance of a cervical mass with medullary compromise.

Birt-Hogg-Dubé Syndrome

A 45-year-old woman with a history of renal carcinoma was observed for facial, cervical and truncal flesh-colored papules. Relatives had similar skin findings and a brother had repeated episodes of pneumothorax. The computerized tomography scan revealed multiple cysts on both lungs. A skin biopsy revealed a perifollicular fibroma. The clinical diagnosis of Birt-Hogg-Dubé syndrome (BHDS) was corroborated by identification of a novel frameshift c.573delGAinsT (p.G191fsX31) mutation in heterozygosity on exon 6 of the folliculin gene. The presence of multiple and typical benign hair follicle tumors highlights the role of the dermatologist in the diagnosis of this rare genodermatosis that is associated with an increased risk of renal cell cancer and pulmonary cysts, warranting personal and familial follow-up and counseling.

Aortic and Tricuspid Endocarditis in Hemodialysis Patient with Systemic and Pulmonary Embolism

This is a case report of a 43-year-old Caucasian male with end-stage renal disease being treated with hemodialysis and infective endocarditis in the aortic and tricuspid valves. The clinical presentation was dominated by neurologic impairment with cerebral embolism and hemorrhagic components. A thoracoabdominal computerized tomography scan revealed septic pulmonary embolus. The patient underwent empirical antibiotherapy with ceftriaxone, gentamicin and vancomycin, and the therapy was changed to flucloxacilin and gentamicin after the isolation of S. aureus in blood cultures. The multidisciplinary team determined that the patient should undergo valve replacement after the stabilization of the intracranial hemorrhage; however, on the 8th day of hospitalization, the patient entered cardiac arrest due to a massive septic pulmonary embolism and died. Despite the risk of aggravation of the hemorrhagic cerebral lesion, early surgical intervention should be considered in high-risk patients.

Histoplasmosis presenting as addisonian crisis in an immunocompetent host

A 71-year-old man with presumptively treated pulmonary tuberculosis ten years earlier and previous alcoholism presented with adrenal insufficiency. HIV serology was negative. A computerized tomography scan of the abdomen showed enlarged right adrenal. He recovered after emergency treatment with hydrocortisone IV. Right adrenalectomy was performed. Histoplasmosis was diagnosed and the patient was treated with itraconazole, corticosteroid replacement, and discharged with good health.

Premature thelarche: identification of clinical and laboratory data for the diagnosis of precocious puberty

PURPOSE: Two groups of girls with premature breast development were studied retrospectively. We tried to identify clinical, radiological, and hormonal parameters that could distinguish between a benign, nonprogressive premature thelarche and a true precocious puberty. METHODS: The clinical outcome of 88 girls with breast enlargement before 6.1 years of age was analyzed. Taking into account the progression of their sexual maturation, we allocated the children into 2 groups: "Isolated Premature Thelarche" (n = 63) and "Precocious Puberty" (n = 25) groups. Chronological and bone ages, height and growth velocity centiles, computerized tomography of hypothalamus-pituitary area, pelvic ultrasonography, gonadotropin response to luteinizing hormone-releasing hormone stimulation as well as basal levels of luteinizing hormone, follicle-stimulating hormone, estradiol, and prolactin were studied in both groups. Statistical analysis were performed using the Student t test to compare the sample means. Fisher's exact test and chi² test were used to analyze the nonparametric variables. RESULTS: Isolated premature thelarche most frequently affected girls younger than 2 years who presented exaggerated follicle-stimulating hormone response to luteinizing hormone-releasing hormone stimulation test. The precocious puberty group had higher initial stature, accelerated growth rate and bone age, increased uterine and ovarian volumes, high spontaneous luteinizing hormone levels by immunofluorimetric assay, as well as a high luteinizing hormone response and peak luteinizing hormone/follicle-stimulating hormone ratio after luteinizing hormone-releasing hormone stimulation. CONCLUSION: At initial presentation, girls who undergo true precocious puberty present advanced bone age, increased uterine and ovarian volumes in addition to breast enlargement, as well as an luteinizing hormone-predominant response after a luteinizing hormone-releasing hormone stimulation test.