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Lorenzi A.T.,Barretos Cancer Hospital | Fregnani J.H.T.G.,Barretos Cancer Hospital | Possati-Resende J.C.,Barretos Cancer Hospital | Neto C.S.,Barretos Cancer Hospital | And 6 more authors.
Gynecologic Oncology | Year: 2013

Objective. Cervical cancer is the second most common cancer among Brazilian women. High-risk human papillomavirus (hr-HPV) persistence is the primary cause of cervical neoplasia. Early detection of hr-HPV is important for identifying women at risk for developing cervical lesions. Approximately 85% of new cases of cervical cancer worldwide and 50% of the total cervical cancer deaths occurred in developing countries. Here, a newmethodology to support a cervical cancer screening program was evaluated in women from various Brazilian regions. Methods. Two thousand women aged 18-77 years were enrolled in an opportunistic cervical cancer screening programandwere randomized into self-vaginal or health professional-guided cervical sampling groups. The Qiagen careHPV™testwas performed on all samples. Pap testswere performed on all women using liquid-based cytology. Results. Positive hr-HPV resultswere obtained in 12.3% (245/2000) ofwomen; similar rateswere observed in self- or health professional-collected samples. Eighty-nine percent (1719/2000) of cervical cytologies classified as normal were negative to hr-HPV. Among the cytological samples, 36.6% classified as ASC-US+ were positive to hr-HPV, 78.8% were LSIL and 75.0% were HSIL. Conclusions. Self-sampled and health professional-sampled vaginal/cervical specimens did not differ in their rates of detection of hr-HPV. Therefore, HPV DNA testing in self-sampled vaginal cells is an alternative to primary screening in low-resource settings. © 2013 Elsevier Inc. All rights reserved.


PubMed | Federal University of São Paulo, Santa Casa de Sao Paulo Medical School, University of Sao Paulo and King's College London
Type: | Journal: Journal of psychiatric research | Year: 2015

Schizophrenia is a neurodevelopmental disorder that produces abnormalities across different brain regions. Measuring structural covariance with MRI is a well-established approach to investigate common changes in distinct systems. We investigated structural covariance in schizophrenia in a large Brazilian sample of individuals with chronic schizophrenia (n = 143), First Episode Psychosis (n = 32), and matched healthy controls (n = 82) using a combination of graph analysis and computational neuroanatomy. Firstly, we proposed the connectivity-closeness and integrity-closeness centrality measures and them compared healthy controls with chronic schizophrenia regarding these metrics. We then conducted a second analysis on the mapped regions comparing the pairwise difference between the three groups. Our results show that compared with controls, both patient groups (in pairwise comparisons) had a reduced integrity-closeness in pars orbitalis and insula, suggesting that the relationship between these areas and other brain regions is increased in schizophrenia. No differences were found between the First Episode Psychosis and Schizophrenia groups. Since in schizophrenia the brain is affected as a whole, this may mirror that these regions may be related to the generalized structural alteration seen in schizophrenia.


Vasconcelos A.R.,University of Sao Paulo | Yshii L.M.,University of Sao Paulo | Viel T.A.,University of Sao Paulo | Buck H.S.,Santa Casa de Sao Paulo Medical School | And 4 more authors.
Journal of Neuroinflammation | Year: 2014

Background: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Methods: Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses.Results: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels.Conclusions: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection. © 2014 Vasconcelos et al.; licensee BioMed Central Ltd.


Younes R.N.,University of Sao Paulo | Fares A.L.,Santa Casa de Sao Paulo Medical School | Sardenberg R.A.S.,Hospital Sirio Libanes | Gross J.L.,Hospital AC Camargo
Minerva Chirurgica | Year: 2012

Aim. Isolated pulmonary metastases from head and neck cancer occur in 20%-30% of patients affected by head and neck neoplams. Surgical resection is well accepted as a standard approach to treat metastases from head and neck cancer isolated to the lungs. Many studies reported overall five-year survival ranging from 20% to 30%. The aim of this study is to determine demographics and clinical treatment-related variables associated with longterm (60-month) overall survival in patients with lung metastases undergoing pulmonary metastasectomy from head and neck tumors. Methods. A retrospective review was performed of patients who were admitted with lung metastases and underwent thoracotomy for resection after treatment of the primary tumor. Data were collected regarding primary tumor features, demographics, treatment, and outcome. Results. Median follow-up time of all patients was 36.4 months (range: 0-288 months). The postoperative complication rate was 14.4%, and the 30-day mortality rate was 0%. The 60-month overall survival rate for all patients was 35.5%. Multivariate analysis identified the number of nodules at CT scan, the disease-free interval, and histological type as independent prognostic factors for overall survival. Conclusion. Lung metastasectomy is a safe and potentially curative procedure for patients with treated primary tumors. A select group of patients can achieve long-term survival after lung resection.


PubMed | Santa Casa de Sao Paulo Medical School and University of Sao Paulo
Type: | Journal: Frontiers in endocrinology | Year: 2016

Glucocorticoids (GCs) are potent anti-inflammatory compounds that have been extensively used in clinical practice for several decades. GCs effects on inflammation are generally mediated through GC receptors (GRs). Signal transduction through these nuclear receptors leads to dramatic changes in gene expression programs in different cell types, typically due to GR binding to DNA or to transcription modulators. During the last decade, the view of GCs as exclusive anti-inflammatory molecules has been challenged. GR negative interference in pro-inflammatory gene expression was a landmark in terms of molecular mechanisms that suppress immune activity. In fact, GR can induce varied inhibitory molecules, including a negative regulator of Toll-like receptors pathway, or subject key transcription factors, such as NF-B and AP-1, to a repressor mechanism. In contrast, the expression of some acute-phase proteins and other players of innate immunity generally requires GR signaling. Consequently, GRs must operate context-dependent inhibitory, permissive, or stimulatory effects on host defense signaling triggered by pathogens or tissue damage. This review aims to disclose how contradictory or comparable effects on inflammatory gene expression can depend on pharmacological approach (including selective GC receptor modulators; SEGRMs), cell culture, animal treatment, or transgenic strategies used as models. Although the current view of GR-signaling integrated many advances in the field, some answers to important questions remain elusive.


Melo M.R.,Santa Casa de Sao Paulo Medical School | Clark S.,Amcare Labs | Barrio D.,Technical Operations
Clinical Chemistry and Laboratory Medicine | Year: 2011

Clinical laboratories provide an invaluable service to millions of people around the world in the form of quality diagnostic care. Within the clinical laboratory industry the impetus for change has come from technological development (miniaturization, nanotechnology, and their collective effect on point-of-care testing; POCT) and the increasingly global nature of laboratory services. Potential technological gains in POCT include: the development of bio-sensors, microarrays, genetics and proteomics testing, and enhanced web connectivity. In globalization, prospective opportunities lie in: medical tourism, the migration of healthcare workers, cross-border delivery of testing, and the establishment of accredited laboratories in previously unexplored markets. Accompanying these impressive opportunities are equally imposing challenges. Difficulty transitioning from research to clinical use, poor infrastructure in developing countries, cultural differences and national barriers to global trade are only a few examples. Dealing with the issues presented by globalization and the impact of developing technology on POCT, and on the clinical laboratory services industry in general, will be a daunting task. Despite such concerns, with appropriate countermeasures it will be possible to address the challenges posed. Future laboratory success will be largely dependent on one's ability to adapt in this perpetually shifting landscape. © 2011 by Walter de Gruyter Berlin New York.


PubMed | University of Porto, Hospital Italiano Of Buenos Aires, Federal University of Rio de Janeiro, Santa Casa de Sao Paulo Medical School and Liga Norte Riograndense Contra o Cancer
Type: Clinical Trial, Phase III | Journal: Annals of hematology | Year: 2016

The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9% with MPT, 89.7% with CTD, and 68.7% with TD (p=0.056 for the comparison between MPT and CTD). The median PFS was 24.1months for MPT, 25.9months for CTD, and 21.5months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p=0.046) and with performance status of 0 or 1 (p=0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available.


Sutti R.,Santa Casa de Sao Paulo Medical School | Tamascia M.L.,University of Campinas | Hyslop S.,University of Campinas | Rocha-e-Silva T.A.A.,Santa Casa de Sao Paulo Medical School
Journal of Venomous Animals and Toxins Including Tropical Diseases | Year: 2014

Background: Venom hyaluronidase (Hyase) contributes to the diffusion of venom from the inoculation site. In this work, we purified and characterized Hyase from the venom ofVitalius dubius(Araneae, Theraphosidae), a large theraphosid found in southeastern Brazil. Venom obtained by electrical stimulation of adult male and femaleV. dubiuswas initially fractionated by gel filtration on a Superdex® 75 column. Active fractions were pooled and applied to a heparin-sepharose affinity column. The proteins were eluted with a linear NaCl gradient.Results: Active fractions were pooled and assessed for purity by SDS-PAGE and RP-HPLC. The physicochemical tests included optimum pH, heat stability, presence of isoforms, neutralization by flavonoids and assessment of commercial antivenoms. Hyase was purified and presented a specific activity of 148 turbidity-reducing units (TRU)/mg (venom: 36 TRU/mg; purification factor of ~4). Hyase displayed a molecular mass of 43 kDa by SDS-PAGE. Zymography in hyaluronic-acid-containing gels indicated an absence of enzyme isoforms. The optimum pH was 4-5, with highest activity at 37°C. Hyase was stable up to 60°C; but its activity was lost at higher temperatures and maintained after several freeze-thaw cycles. The NaCl concentration (up to 1 M) did not influence activity. Hyase had greater action towards hyaluronic acid compared to chondroitin sulfate, and was completely neutralized by polyvalent antiarachnid sera, but not by caterpillar, scorpion or snakes antivenoms.Conclusion: The neutralization by arachnid but not scorpion antivenom indicates that this enzyme shares antigenic epitopes with similar enzymes in other spider venoms. The biochemical properties of this Hyase are comparable to others described. © 2014 Sutti et al.


Araujo J.L.V.,Santa Casa Medical School | De Aguiar G.B.,Santa Casa Medical School | Do Prado Aguiar U.,Santa Casa Medical School | Mayrink D.,Santa Casa de Sao Paulo Medical School | And 2 more authors.
Journal of Craniofacial Surgery | Year: 2012

Malignant chondroid syringoma is a mixed cutaneous tumor, with epithelial and mesenchymal components, which compromises principally the trunk and extremities. This lesion is quite rare, with few cases related in the literature and no publications demonstrating its involvement of the central nervous system. Histologically, owing to its mixed origin, it represents a lesion that is difficult to recognize, often being confused with basocellular carcinoma. We report the case of a female patient, carrier of malignant chondroid syringoma in the occipital region, with invasion of the central nervous system, who was submitted to surgical excision of the lesion at our service. We also made a brief revision of the literature on the theme. Copyright © 2012 by Mutaz B. Habal, MD.


PubMed | Hospital Alemao Oswaldo Cruz and Santa Casa de Sao Paulo Medical School
Type: Journal Article | Journal: Case reports in oncology | Year: 2016

Splenic tumors are not frequent. Blood vessel neoplasms are a rare category of tumors and have an extremely low incidence in the spleen. This case report aims to describe a 57-year-old woman in whom a routine imaging examination had shown splenic cysts. During her follow-up, the cysts became larger and increased in number. A diagnostic splenectomy was performed and its analysis showed a rare splenic angiosarcoma.

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