Nelson Pires Ferreira

Irmandade da Santa Casa da Misericórdia de Santos, Santos, São Paulo, Brazil

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Publications (35)44.9 Total impact

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    ABSTRACT: To evaluate the ability of post-transsphenoidal pituitary surgery (TSS) serum cortisol levels (s-cortisol) to predict surgical remission and recurrence of Cushing's disease (CD). One hundred and three CD patients from a tertiary referral centre were prospectively analyzed over 6.0 ± 4.8 years of follow-up. Twenty patients received perioperative glucocorticoids as routine care and had s-cortisol measured 10 to 12 days after TSS (Protocol I). Eighty-six patients (91 surgeries) had s-cortisol measured at 6, 12, 18, 24 h, 48 h, and 10 to 12 days after TSS, and received glucocorticoids only in case of adrenal insufficiency (Protocol II). Remission (clinical signs and symptoms of adrenal insufficiency (or hypocortisolism) plus cortisol <3 μg/dL on the 1-mg overnight test [OT] and/or normal free urinary cortisol) during follow-up. Recurrence was defined as loss of remission criteria at least 1 year after TSS. The remission rate after first TSS was 80%; 8% had recurrence. An s-cortisol nadir ≤3.5 μg/dL within 48 h after TSS had sensitivity of 73%, specificity and positive predictive value (PPV) of 100% and negative predictive value (NPV) of 60% and an s- cortisol nadir ≤5.7 μg/dL within 10 to 12 days of TSS had specificity and PPV of 100% and sensitivity of 91% NPV of 78% for CD remission. At hospital discharge, the s-cortisol nadir within 48 h after TSS was already able to predict surgical remission for some patients and the s-cortisol nadir within 10 to 12 days of TSS was able to predict cohort-wide surgical remission. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2013; · 3.40 Impact Factor
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    ABSTRACT: BACKGROUND: Prolactin (PRL) is a hormone synthesized in both the pituitary gland and extrapituitary sites. It has been associated with the occurrence of neoplasms and, more recently, with central nervous system (CNS) neoplasms. The aim of this study was to evaluate prolactin expression in primary central nervous system tumors through quantitative real-time PCR and immunohistochemistry (IH). RESULTS: Patient mean age was 49.1 years (SD 15.43), and females accounted for 70% of the sample. The most frequent subtype of histological tumor was meningioma (61.5%), followed by glioblastoma (22.9%). Twenty cases (28.6%) showed prolactin expression by immunohistochemistry, most of them females (18 cases, 90%). Quantitative real-time PCR did not show any prolactin expression. CONCLUSIONS: Despite the presence of prolactin expression by IH, the lack of its expression by quantitative real-time PCR indicates that its presence in primary tumors in CNS is not a reflex of local production.
    Journal of Negative Results in BioMedicine 01/2013; 12(1):4. · 1.47 Impact Factor
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    ABSTRACT: Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.
    The Journal of craniofacial surgery 05/2012; 23(3):650-3. · 0.81 Impact Factor
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    ABSTRACT: We aimed at the evaluation of MEG3 and GADD45γ expression in sporadic functioning and clinically non-functioning human pituitary adenomas, morphologically characterized by immunohistochemistry analysis and their association with clinical features. Thirty eight patients who had undergone hypophysectomy at São José Hospital of Irmandade Santa Casa de Misericórdia in Porto Alegre, Brazil, were included in this study. We evaluated tumor-type specific MEG3 and GADD45γ expression by qRT-PCR in the pituitary adenomas, and its association with clinical features, as age, gender and tumor size, obtained from medical records. The patients consisted of 21 males and 17 females and the mean age was 47 ± 14 (mean ± SD), ranging from 18 to 73 years-old. Of these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5 ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45γ expression was significantly lost in most clinically non-functioning adenomas (78 and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both genes at significantly different levels, and, in some cases, with overexpression. There was no significant association between gene expression and the analyzed clinical features. Our results confirm the previous report, which indicated that MEG3 and GADD45γ expression is lost in the majority of human pituitary tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had differences of relative expression levels. The two groups of tumors are probably genetically different and may have a different natural history.
    Pituitary 08/2011; 15(3):420-7. · 2.67 Impact Factor
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    ABSTRACT: Benign intracranial hypertension (Pseudotumor cerebri) has been described as related to the reduction in steroid levels in Cushing's disease (CD), especially after surgical remission. Ketoconazole is a common and effective adjuvant therapy for hypercortisolism, but the major concern is liver enzyme dysfunction. We describe here the case of a 12-year old girl with CD who developed benign intracranial hypertension during treatment with ketoconazole. She presented headache, vomiting, a black spot on her right temporal visual field, and signs of elevated intracranial pressure. Pituitary image was normal on magnetic resonance image (MRI), and all symptoms improved after treatment with acetazolamide. We call attention to the diagnosis of this disorder in CD patients, especially children on ketoconazole treatment, because it could be confounded with adrenal insufficiency and lead to definitive severe visual impairment.
    Arquivos brasileiros de endocrinologia e metabologia 06/2011; 55(4):284-7. · 0.68 Impact Factor
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    ABSTRACT: Pituitary adenomas (PA) occasionally show aggressive behavior, with invasion of the surrounding tissues. The identification of markers able to recognize aggressive PA in early stages remains a challenge. We aimed to determine the expression of a new cell proliferation marker, Mcm2, and the presence of apoptosis in PA, and to evaluate the association of clinicopathological features with the apoptotic and proliferative indices. Additionally, the TGF-beta1 expression, an inducer of apoptosis, was determined. The proliferative index was determined in GH-secreting or clinically nonfunctioning PA using immunohistochemical (IH) methods for Mcm2 and Ki-67 antigens. The apoptosis was assessed by the TUNEL method and the TGF-beta1 expression by IH. A significant positive correlation was found between log Mcm2 index and log Ki-67 index (p < 0.001). Mcm2 and Ki-67 detected a similar number of proliferating cells. Mcm2 index showed a significant association with tumor extension (p = 0.02), but not with tumor invasion. Apoptosis was detected in 17% of the adenomas, with a maximum apoptotic index of 0.77%. Immunoreactivity to TGF-beta1 was observed in 77% of the adenomas, showing an association with tumor extension. We concluded that, in this sample, Mcm2 was similar to Ki-67 in the identification of the proliferating cells and that apoptosis was rare.
    Endocrine Pathology 02/2010; 21(1):32-9. · 1.60 Impact Factor
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    ABSTRACT: As a consequence of the progressive evolution of neurosurgical techniques, there has been increasing concern with the esthetic aspects of burr holes. Therefore, the objective of this study was to compare the use of cortical bone graft and bone dust for correcting cranial deformities caused by neurosurgical trephines. Twenty-three patients were enrolled for cranial burr hole reconstruction with a 1-year follow-up. A total of 108 burr holes were treated; 36 burr holes were reconstructed with autogenous cortical bone discs (33.3%), and the remaining 72 with autogenous wet bone powder (66.6%). A trephine was specifically designed to produce this coin-shaped bone plug of 14 mm in diameter, which fit perfectly over the burr holes. The reconstructions were studied 12 months after the surgical procedure, using three-dimensional quantitative computed tomography. Additionally, general and plastic surgeons blinded for the study evaluated the cosmetic results of those areas, attributing scores from 0 to 10. The mean bone densities were 987.95 ± 186.83 Hounsfield units (HU) for bone fragment and 473.55 ± 220.34 HU for bone dust (P < 0.001); the mean cosmetic scores were 9.5 for bone fragment and 5.7 for bone dust (P < 0.001). The use of autologous bone discs showed better results than bone dust for the reconstruction of cranial burr holes because of their lower degree of bone resorption and, consequently, better cosmetic results. The lack of donor site morbidity associated with procedural low cost qualifies the cortical autograft as the first choice for correcting cranial defects created by neurosurgical trephines.
    Surgical Neurology International 01/2010; 1:91. · 1.18 Impact Factor
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    ABSTRACT: Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross-sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08). Behavior pattern differences observed between aromatase expression, present in normal tissues and absent in meningiomas, and estrogen and androgen hormone receptors, absent in normal tissues and present in meningiomas, suggest that there is heterogeneity in modulation by sex steroids in the development of these tumors.
    Neuropathology 09/2009; 30(1):44-9. · 1.91 Impact Factor
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    Arquivos de neuro-psiquiatria 07/2009; 67(2A):308-10. · 0.55 Impact Factor
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    Arquivos de neuro-psiquiatria 04/2009; 67(1):127-9. · 0.55 Impact Factor
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    ABSTRACT: Angiogenesis, a fundamental process for the development and growth of a tumor, is less expressive in adenomas than in the normal pituitary tissue. There is controversy about the behavior of angiogenesis as a function of hormonal secretion or other characteristics of pituitary tumors. Endoglin (CD105) is a proliferation-associated antigen on endothelial cells, as well as an endothelial progenitor cell marker. We used the anti-endoglin antibody, a glycoprotein expressed in endothelial cells and conjunctive tissue, as a new marker particularly associated with neovascularization, in order to determine microvascular density (MVD) in pituitary adenomas. There were 77 samples, 31 males and 46 females, carriers of micro- (n = 24) or macroadenomas (n = 53). No significant difference was found in MVD concerning the variables of age, clinical presentation, and immunohistochemical phenotype or tumor size. MVD in males (median 5.4) was significantly higher (P = 0.001) than in females (median 3.0). Cell proliferation, as evaluated by the MIB-1 antibody (a cellular proliferation index [Ki-67 antigen], which is present in all stages of the cellular cycle except for the resting cells), ranged from 0% to 19.58%. No correlation was found between MIB-1 and MVD. It is possible to infer that the lower MVD found in pituitary adenomas in females reflects an inhibitory estrogen action on TGF-beta1, a protein involved in vascular remodeling. Because of its role as a TGF receptor ligand, endoglin proved to be sensitive in detecting this gender difference in pituitary tumor angiogenesis.
    Neuropathology 08/2008; 29(1):40-4. · 1.91 Impact Factor
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    Guilherme Rollin, Nelson Pires Ferreira, Mauro A Czepielewski
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    ABSTRACT: Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.
    Arquivos Brasileiros de Endocrinologia & Metabologia 12/2007; 51(8):1355-61. · 0.88 Impact Factor
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    ABSTRACT: We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushing's disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 microg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis.
    Arquivos Brasileiros de Endocrinologia & Metabologia 12/2007; 51(8):1362-72. · 0.88 Impact Factor
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    ABSTRACT: A case of presentation of Rathke cyst is reported, uncommon because of its precocity, with endocrinologic clinical manifestation of diabetes insipidus and preservation of anterior pituitary function. As there was no clinical suspicion or imaging evidence of this diagnosis, the female patient was submitted to transsphenoidal surgery for pituitary microadenomectomy. Pathologic examination diagnosed Rathke cyst. After the intervention, diabetes insipidus persisted. The possibility of Rathke cyst should be raised in the differential diagnosis of nonfunctioning pituitary adenomas.
    The Endocrinologist 04/2007; 17(3):154-156. · 0.12 Impact Factor
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    ABSTRACT: The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.
    Brain Tumor Pathology 02/2007; 24(2):41-6. · 1.58 Impact Factor
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    ABSTRACT: A pituitary abscess is a rare pathology, but it must be considered when evaluating sellar masses, since its prognosis depends on surgical drainage and on the use of specific antibiotics. The main clinical manifestation is chronic headache, and it is not always associated with the identification of a site of infection, which diminishes the probability of including it in diagnostic hypotheses. The case is presented of a patient with a pituitary abscess and a previous history of adenoma that had been operated on, recent onset headache and acquired hypopituitarism whose initial diagnosis was pituitary apoplexy.
    Arquivos Brasileiros de Endocrinologia & Metabologia 01/2007; 50(6):1122-6. · 0.88 Impact Factor
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    ABSTRACT: The purpose of this study is to report a rare case of primary meningeal high grade Burkitt-type lymphoma presenting as the first clinical manifestation of acquired immunodeficiency syndrome. A 38-year-old Caucasian man, with a negative past medical history, sought treatment after experiencing global headache for five days. CT-Scan revealed a right front-temporo-parietal hyperdense subdural expansive mass. A craniotomy was performed and a hard white subdural was microsurgically dissected. Some hours after the surgery, the patient developed hemispheric cerebral edema and intracranial hypertension syndrome. Decompressive craniotomy was performed and the patient had an excellent recovery. Screening blood tests diagnosed human immunodeficiency virus infection. Further investigation ruled out systemic diseases. Eleven days after the initial surgery, the patient developed an acute respiratory failure and sepsis, dying on that day. Pathological studies diagnosed Burkitt-type lymphoma.
    Arquivos de Neuro-Psiquiatria 07/2006; 64(2B):511-5. · 0.83 Impact Factor
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    ABSTRACT: Stereotactic CT-guided biopsy is a valuable and safe procedure for diagnosing intracranial lesions. The objectives of this article are to analyze the diagnostic yield in a series of stereotactic CT-guided brain biopsies and to evaluate whether predictive factors may influence diagnostic yield. The medical records of a series of patients who underwent stereotactic CT-guided brain biopsy from 1993 to 2005 in a neurosurgical center were reviewed. Clinical data were stored and analyzed with Microsoft Access (Microsoft Corp, Seattle, WA) and SPSS V11.0 software (SPSS, Inc, Chicago, IL). The following variables were analyzed: age, sex, anatomopathologic diagnosis, lesion topography and volume, postsurgical complications, and predictive factors that may affect diagnostic yield. One hundred seventy patients (102 males, 68 females; average age, 48.5 years) were analyzed. Stereotactic CT-guided biopsies allowed diagnosis in 157 cases (92%). The most frequent anatomopathologic diagnoses were high-grade glioma (n = 45), low-grade glioma (n = 31), nonspecific inflammatory lesions (n = 19), metastasis (n = 10), and lymphoma (n = 10). The most frequent topographies were frontal (n = 42), basal ganglia (n = 40), and parietal (n = 27) and front-parietal lobes (n = 9). Complications occurred in 5 patients (2.9%). Mortality rate was 1.2% (2 patients). Age had a positive impact, whereas female sex negatively affected diagnostic yield. All other predictive factors analyzed were not significant. Stereotactic CT-guided brain biopsies performed presented acceptable anatomopathologic diagnostic rate. Age had a positive impact, whereas female sex negatively affected diagnostic yield in this series.
    Surgical Neurology 02/2006; 65 Suppl 1:S1:27-1:32. · 1.67 Impact Factor
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    ABSTRACT: Craniosynostosis, a premature fusion of cranial sutures, can happen as an isolated defect (nonsyndromic) or as part of a syndrome. It may lead to raised intracranial pressure and deformity of both the cranial and facial skeletons. Early surgery is usually the best treatment choice. The aim of this study was to review the experience of a multidisciplinary staff with the surgical treatment of nonsyndromic craniosynostosis. All the nonsyndromic craniosynostosis cases treated surgically from 1991 to 2005 at 2 neurosurgical centers were reviewed. The variables analyzed were sex, age, weight, type of deformity, estimated volemia, surgical technique, surgical time, blood loss, PO hospitalization time, and complications. All data were stored in a database and analyzed with Microsoft Access (Microsoft Corp, Seattle, WA) and SPSS V11.0 (SPSS, Inc, Chicago, IL). The sample consisted of 120 patients (70 males, 50 females). Six patients were excluded because of their atypical timing of treatment (average age, 72 months). The final average age was 7.08 months (variation, 1-18), and the average weight was 7.8 kg. The types of deformities found were scaphocephaly (n = 54, 45%), plagiocephaly (n = 27, 22%), trigonocephaly (n = 19, 16%), brachycephaly (n = 16, 13%), and oxycephaly (n = 4, 3%). The mean surgical time was 186 minutes and the mean PO hospitalization time was 6.8 days. The mortality on this series was 2.6% (3 patients). In the last operated cases, a significant improvement in morbid-mortality was observed. A multidisciplinary approach, including neurosurgeons, neurologists, and pediatricians, and appropriate training of the clinical surgical staff can minimize the risks and decrease the complications in the treatment of craniosynostosis, leading to a satisfactory outcome.
    Surgical Neurology 02/2006; 65 Suppl 1:S1:22-1:26; discussion S1:26. · 1.67 Impact Factor
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    ABSTRACT: Pituitary Abscess Simulating Apoplexy. A pituitary abscess is a rare pathology, but it must be considered when evaluating sellar masses, since its prognosis depends on surgical drainage and on the use of specific antibiotics. The main clinical mani- festation is chronic headache, and it is not always associated with the identification of a site of infection, which diminishes the probability of including it in diagnostic hypotheses. The case is presented of a patient with a pituitary abscess and a previous history of adenoma that had been operated on, recent onset headache and acquired hypopitu- itarism whose initial diagnosis was pituitary apoplexy. (Arq Bras Endocrinol Metab 2006;50/6:1122-1126)
    Arquivos Brasileiros De Endocrinologia E Metabologia - ARQ BRAS ENDOCRINOL METABOL. 01/2006; 50(6).

Publication Stats

181 Citations
44.90 Total Impact Points

Institutions

  • 2007–2013
    • Irmandade da Santa Casa da Misericórdia de Santos
      Santos, São Paulo, Brazil
  • 2005–2013
    • Universidade Federal do Rio Grande do Sul
      • Faculty of Medicine
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
    • Santa Casa de Porto Alegre
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 2011
    • Hospital De Clínicas De Porto Alegre
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil
  • 1992–2010
    • Universidade Federal de Ciências da Saúde de Porto Alegre
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil