Browsing by Author "Gonzalez, Sergio"

Now showing 1 - 18 of 18
  • Thumbnail Image
    Item
    Actinomycotic mycetoma due to Actinomadura madurae
    (SOC CHILENA INFECTOLOGIA, 2012) Jerez, Richard; Schafer, Fabiola; Fich, Felix; Garcia, Patricia; Leon, Pilar; Gonzalez, Sergio
    Mycetoma is a chronic, granulomatous, subcutaneous, inflammatory lesion caused by true fungi (eumycetoma) or filamentous bacteria (actinomycetoma). Mycetoma commonly affects young people between 20 and 40 years old. The most common affected site is the foot. The characteristic clinical triad is tumefaction, draining sinuses and discharging grains. We report a healthy 31-year-old male, with a 6-year history of a progressive inflammatory tumor associated with sinus tracts and granules on his left sole. Actinomycetoma was suspected. The clinical diagnosis was confirmed by microbiological and histopathological study. Polymerase chain reaction and DNA sequencing identified Actinomadura madurae. To our knowledge, this is the second case of mycetoma reported in Chile. Our report emphasizes the need to consider this diagnosis in patients with chronic granulomatous disease associated with sinus tracts, fistulas and grains.
  • Thumbnail Image
    Item
    Allelotyping, Microsatellite Instability, and BRAF Mutation Analyses in Common and Atypical Melanocytic Nevi and Primary Cutaneous Melanomas
    (LIPPINCOTT WILLIAMS & WILKINS, 2009) Uribe, Pablo; Wistuba, Ignacio I.; Gonzalez, Sergio
    Loss of heterozygosity (LOH) in several chromosomal regions is found in melanoma, and it has been partially studied in nevi. BRAF mutations are found in melanoma and nevi and in colorectal cancer are linked to mismatch repair deficiency. We studied early genetic events involved in melanomagenesis through analysis of allelic loss, microsatellite instability (MSI), and BRAF mutations.
  • Thumbnail Image
    Item
    Angiolymphoid hyperplasia with eosinophilia showing prominent granulomatous and fibrotic reaction: A morphological and immunohistochemical study
    (LIPPINCOTT WILLIAMS & WILKINS, 2006) Macarenco, Ricardo S.; do Canto, Abaete Leite; Gonzalez, Sergio
    Angiolymphoid hyperplasia with eosinophilia is an uncommon condition that usually presents in early to middle-aged adults as multiple red nodules or plaques, most commonly on the head and neck. It can also occur on the trunk and limbs, and rarely at other sites such as the breast and oral mucosa. Although one-third of these lesions recur, surgical excision is curative. The histopathological hallmark is the presence of blood vessels with plump epithelioid endothelial cells. The nonvascular component consists of histiocytes, plasma cells, eosinophils, and lymphocytes. The occurrence of numerous giant cells in the stroma of angiolymphoid hyperplasia with eosinophilia is extremely unusual and such a finding in association with diffuse granulomatous/fibrous reaction has not been reported. We describe such a lesion that developed in the wrist of a 34-year-old pregnant female.
  • Thumbnail Image
    Item
    Comparative analysis of loss of heterozygosity and microsatellite instability in adult and pediatric melanoma.
    (2005) Uribe González, Pablo Francisco; Wistuba, Ignacio I.; Solar, Antonieta; Balestrini, Claudia; Perez-Cotapos, Maria Luisa; Gonzalez, Sergio
    Although 0.3% of melanomas occur in children, the incidence has risen in past decades. In adult melanoma, some chromosomal regions in 1p, 6q, 9p, 10q, and 11q are frequently deleted. Microsatellite instability (MSI), which reflects impaired DNA repair, has been found at low levels in adult melanoma and melanocytic nevi. To investigate the molecular changes in pediatric melanoma, a screening for loss of heterozygosity and microsatellite instability was performed and compared with changes found in adult melanoma. Formalin-fixed, paraffin-embedded tissues from 10 adult melanomas, 9 melanocytic nevi, and 8 pediatric melanomas were microdissected and the DNA was extracted. Loss of heterozygosity and microsatellite instability were evaluated using 13 microsatellite repeat polymorphisms located in 1p36, 1q32, 2p12, 2p22-25, 2q33-37, 9p21, 10q23.3, 11q23, 13q14, 17p13, and 17q21. The overall frequency of loss of heterozygosity was 0.09 for nevi, 0.30 for adult melanoma, and 0.43 for pediatric melanoma (nevi vs. adult melanoma, P = 0.0082; nevi vs. pediatric melanoma, P = 0.0092). Pediatric melanoma has more loss of heterozygosity (44%) in 11q23 than adult melanoma (7%, P = 0.046). The microsatellite instability overall frequency was greater in pediatric melanoma (0.24) than nevi (0.05, P = 0.0031) and adult melanoma (0.09, P = 0.0195). Our findings suggest that pediatric melanoma has a different abnormal pattern than adult melanoma. Pediatric melanoma has more microsatellite instability than adult melanoma. 11q23 could contain genes related to the early age onset of melanoma. The high frequency of microsatellite instability is coincidental with the finding of higher levels of microsatellite instability in pediatric brain tumors and could play a role in the pathogenesis of pediatric melanoma.
  • No Thumbnail Available
    Item
    Complete response to immunotherapy plus chemotherapy after an unusual clinical response to afatinib and stereotactic radiosurgery in a patient with metastatic EGFR-mutant non–small-cell lung cancer
    (2020) Pizarro, Gonzalo; Pinto, Mauricio P.; Muñoz-Medel, Matías; Cordova-Delgado, Miguel; Bravo, M. Loreto; Nervi, Bruno; Sánchez, César; Ibañez, Carolina; Peña, José; Walbaum, Benjamín; Madrid, Jorge; Briones, Juan; Koch, Erica; Valbuena, Jose; Gonzalez, Sergio; Gejman, Roger; Acevedo, Francisco; Mondaca, Sebastian; Garrido, Marcelo; Vines, Eugenio; Galindo, Hector
  • Thumbnail Image
    Item
    Cryptogenic organizing pneumonitis during oxaliplatin chemotherapy for colorectal cancer - Case report
    (AMER COLL CHEST PHYSICIANS, 2007) Garrido, Marcelo; O'Brien, Andres; Gonzalez, Sergio; Clavero, Jose Mignel; Orellana, Eric
    The patient presented here is a 30-year-old woman who underwent anterior resection for the initial treatment of rectal cancer. A postoperative study showed a single liver metastasis. The patient received adjuvant pelvic radiotherapy with concomitant 5-fluorouracil (5-FU) treatment followed by liver metastasectomy 6 weeks after the completion of radiation therapy and chemotherapy. Adjuvant therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX 4 regimen) was continued. The initial five cycles were well tolerated with the occurrence of only paresthesia that did not interfere with function. After the sixth cycle of the treatment, progressive dyspnea and persistent cough developed in the patient, although her clinical history was negative for lung disease. A chest radiograph revealed diffuse bilateral interstitial infiltrates, and a chest CT scan showed bilateral alveolar infiltrates predominant in the right lung. Lung biopsy by video-assisted thoracoscopy was performed, and the histologic report showed cryptogenic organizing pneumonitis (COP). Prednisone therapy (1 mg/kg/d) resulted in a very good clinical response. In fact, the patient had complete remission of respiratory symptoms including cough and dyspnea after 4 days of treatment, and the chest CT scan showed complete resolution of lung infiltrates after 4 weeks. One month later, the patient continued adjuvant treatment with six cycles of 5-FU, leucovorin, and irinotecan (ie, the FOLFIRI regimen) without complications. Thus, oxiplatin was implicated as the likely cause of this drug-induced lung toxicity, which is a very rare complication associated with platins. Diffuse interstitial lung disease, particularly COP, has been described following the administration of the cytotoxic agents bleomycin and busulfan, but a connection to oxaliplatin has not been reported before this case.
  • Thumbnail Image
    Item
    Dysferlinopathy in Chile: Evidence of Two Novel Mutations in the First Reported Cases
    (MARY ANN LIEBERT, INC, 2009) Bevilacqua, Jorge A.; Krahn, Martin; Pedraza, Luis; Gejman, Roger; Gonzalez, Sergio; Levy, Nicolas
    We describe two Chilean patients with dysferlinopathy, a 32-year-old man with Miyoshi's distal myopathy and a 29-year-old woman with a proximodistal phenotype. Absence of dysferlin in frozen muscle biopsy allowed diagnostic confirmation. In these two patients, two mutations not previously identified in other populations were found: a homozygous c.1948delC (p. Leu650TyrfsX6) was found in the male patient; the heterozygous mutation c.1276G>A (p.Gly426Arg) was found in the female patient in association with the previously reported c.2858dupT (p.Phe954ValfsX2). To our knowledge, this is the first time that mutations in DYSF are identified in native Chileans. Our findings suggest the possibility that mutations in the DYSF gene were present in the Native American population before colonization.
  • Thumbnail Image
    Item
    Efficacy of topical photodynamic therapy for keratoacanthomas: A case-series of four patients
    (MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2012) Farias, Maria M.; Hasson, Ariel; Navarrete, Cristian; Nicklas, Claudia; Garcia Huidobro, Isidora; Gonzalez, Sergio
    Topical photodynamic therapy (PDT) is an excellent treatment option for various non-melanoma skin cancers and precancerous lesions, including actinic keratosis, Bowen's disease, and basal cell carcinoma. The clinical use of PDT includes a broad range of neoplastic, inflammatory, and infectious skin diseases. There is also anecdotal evidence suggesting the efficacy of PDT for the treatment of keratoacanthomas (KA). We report a case-series of four patients with solitary KA confirmed by histology, treated with topical PDT with methylaminolevulinic acid (MAL) cream. After three sessions of PDT, the lesions completely disappeared. There was no evidence of recurrence and excellent cosmetic outcome was achieved after three years of follow-up. Topical photodynamic therapy with MAL can be a therapeutic alternative for KA with good clinical and cosmetic outcomes.
  • Thumbnail Image
    Item
    Impaired cardiac autophagy in patients developing postoperative atrial fibrillation
    (MOSBY-ELSEVIER, 2012) Garcia, Lorena; Verdejo, Hugo E.; Kuzmicic, Jovan; Zalaquett, Ricardo; Gonzalez, Sergio; Lavandero, Sergio; Corbalan, Ramon
    Objectives: Postoperative atrial fibrillation (POAF) is a common complication after on-pump heart surgery. Several histologic abnormalities, such as interstitial fibrosis and vacuolization, have been described in atrial samples from patients developing POAF. This ultrastructural remodeling has been associated with the establishment of a proarrhythmic substrate. We studied whether atrial autophagy is activated in patients who develop POAF.
  • No Thumbnail Available
    Item
    Influence of socioeconomic status on clinical outcomes of malignant melanoma in Chile: A cross-sectional study
    (2015) Molgó Novell, Montserrat; Andino Navarrete, Romina; Silva, Maria Jesus; Navajas Galimany, Lucas; Sazunic, Ivo; Gonzalez, Sergio
  • Thumbnail Image
    Item
    Lack of association between BRAF mutation and MAPK ERK activation in melanocytic nevi
    (NATURE PUBLISHING GROUP, 2006) Uribe, Pablo; Andrade, Leonardo; Gonzalez, Sergio
    The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase signaling pathway can be activated through mutations of V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60%), common nevi (CN) (73-82%), and atypical nevi (AN) (52-80%). MAPK activation has been reported between 0 and 22% in nevi, and 86% of primary melanoma, without any knowledge of BRAF mutational status. We studied the correlation of MAPK activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma. Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29% of CN, 48% of AN, and 85% of PM. BRAF mutation was found in 67% of CN, 62% of AN, and 58% of PM. In all, 23% of CN, 54% of AN, and 93% of PM with BRAF mutation have activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi, and it is suggested that other events are needed to induce MAPK activation, that is, B-Raf overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase inhibitors.
  • Thumbnail Image
    Item
    Leukocytoclastic Vasculitis as Early Manifestation of Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma of the Elderly
    (LIPPINCOTT WILLIAMS & WILKINS, 2012) Zoroquiain, Pablo; Gonzalez, Sergio; Molgo, Montserrat; Rodriguez, Alejandra; Valbuena, Jose R.
    Extensive necrotizing vasculitis (ENV) is a rare paraneoplastic phenomenon, and the majority of cases reported are associated with hematolymphoid neoplasms. Histologically, most cases of ENV represent leukocytoclastic vasculitis (LCV). Here we report the clinicopahological features of a 68-year-old man with ENV associated to a Epstein Barr virus-positive diffuse large B-cell lymphoma (EBV+DLBCL) of the elderly, a newly recognized lymphoproliferative disorder, most likely representing a paraneoplastic manifestation. The patient was treated with standard chemotherapy regimen for malignant lymphoma. Due to the extensive involvement of the extremities by ENV, surgical debridement was not feasible and a novel therapy based on CHITOSAN apposits was initiated with overall good response and subsequent re-epithelization of the skin lesions. The patient died of sepsis secondary to a Pseudomona pneumonia 17 months after diagnosis.
  • Thumbnail Image
    Item
    Linear IgA bullous dermatosis: report of five cases in Chile
    (WILEY, 2012) Sandoval, Mauricio; Magdalena Farias, Maria; Gonzalez, Sergio
    Background Linear IgA bullous dermatosis (LABD) is an acquired autoimmune sub-epidermal vesiculobullous disease characterized by continuous linear IgA deposit on the basement membrane zone, as visualized on direct immunofluorescence microscopy. LABD can affect both adults and children. The disease is very uncommon, with a still unknown incidence in the South American population. Materials and methods All confirmed cases of LABD by histological and immunofluorescence in our hospital were studied. Results The confirmed cases were three females and two males, aged from 8 to 87 years. Precipitant events associated with LABD were drug consumption (non-steroid inflammatory agents in two cases) and ulcerative colitis (one case). Most of our patients were treated with dapsone, resulting in remission. Discussion Our series confirms the heterogeneous clinical features of this uncommon disease in concordance with a larger series of patients reported in the literature.
  • Thumbnail Image
    Item
    Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha
    (WILEY-BLACKWELL, 2008) Fernandez, Ricardo; Gonzalez, Sergio; Rey, Sergio; Cortes, Paula P.; Maisey, Kevin R.; Reyes, Edison Pablo; Larrain, Carolina; Zapata, Patricio
    In the absence of information on functional manifestations of carotid body (CB) inflammation, we studied an experimental model in which lipopolysaccharide (LPS) administration to pentobarbitone-anaesthetized cats was performed by topical application upon the CB surface or by intravenous infusion (endotoxaemia). The latter caused: (i) disorganization of CB glomoids, increased connective tissue, and rapid recruitment of polymorphonuclear cells into the vascular bed and parenchyma within 4 h; (ii) increased respiratory frequency and diminished ventilatory chemoreflex responses to brief hypoxia (breathing 100% N-2 for 10 s) and diminished ventilatory chemosensory drive (assessed by 100% O-2 tests) during normoxia and hypoxia; (iii) tachycardia, increased haematocrit and systemic hypotension in response to LPS I.V.; and (iv) increased basal frequency of carotid chemosensory discharges during normoxia, but no change in maximal chemoreceptor responses to brief hypoxic exposures. Lipopolysaccharide-induced tachypnoea was prevented by prior bilateral carotid neurotomy. Apoptosis was not observed in CBs from cats subjected to endotoxaemia. Searching for pro-inflammatory mediators, tumour necrosis factor-alpha (TNF-alpha) was localized by immunohistochemistry in glomus and endothelial cells; reverse transcriptase-polymerase chain reaction revealed that the CB expresses the mRNAs for both type-1 (TNF-R1) and type-2 TNF-alpha receptors (TNF-R2); Western blot confirmed a band of the size expected for TNF-R1; and histochemistry showed the presence of TNF-R1 in glomus cells and of TNF-R2 in endothelial cells. Experiments in vitro showed that the frequency of carotid nerve discharges recorded from CBs perfused and superfused under normoxic conditions was not significantly modified by TNF-alpha, but that the enhanced frequency of chemosensory discharges recorded along responses to hypoxic stimulation was transiently diminished in a dose-dependent manner by TNF-alpha injections. The results suggest that the CB may operate as a sensor for immune signals, that the CB exhibits histological features of acute inflammation induced by LPS, that TNF-alpha may participate in LPS-induced changes in chemosensory activity and that some pathophysiological reactions to high levels of LPS in the bloodstream may originate from changes in CB function.
  • Thumbnail Image
    Item
    p16ink4a Expression in Benign and Malignant Melanocytic Conjunctival Lesions
    (SAGE PUBLICATIONS INC, 2012) Zoroquiain, Pablo; Fernandes, Bruno F.; Gonzalez, Sergio; Novais, Gustavo N.; Schalper, Kurt A.; Burnier, Miguel N., Jr.
    Acquired conjunctival melanocytic lesions include nevi, primary acquired melanoses (PAMs), and melanomas. Conjunctival melanoma is a malignant melanocytic neoplasm with a high metastasis and mortality rate. Usually, the diagnosis can be achieved only with routine microscopic analysis, but in some cases, the samples are small or have artifacts. In these cases, complementary studies will be helpful, but currently, there are no well-understood or studied complementary methods. Objective. To analyze the immunohistochemical expression of p16 in conjunctival melanocytic lesions and to assess its potential for differentiating between benign and malignant melanocytic lesions. Methods. Immunohistochemical study against p16ink4a (p16) was performed on paraffin-embedded sections on 45 melanocytic lesions (9 melanomas, 19 nevi, and 2 PAMs with atypia and 15 without atypia). Expression was scored according to the German immunoreactive score (IRS). Results. Expression of p16 IRS differed between nevi, PAMs, and melanomas. The mean IRS for melanomas was 3.3 +/- 1.8 and was lower than those for nevi (7.63 +/- 3.24; P < .05), PAM with atypia (12 +/- 0; P < .05), and PAM without atypia (11 +/- 1.69; P < .05). Lesions with infiltration depths lower than 2 mm showed higher levels of p16. There were no differences between favorable and unfavorable locations. Conclusion. p16 Expression in conjunctival melanocytic lesions showed an expression similar to that in skin and seems to be a good marker to differentiate nevi and PAMs from melanomas. However, additional studies of larger series and follow-up are needed to confirm these findings.
  • Thumbnail Image
    Item
    Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa
    (INFORMA HEALTHCARE, 2010) Conget, Paulette; Rodriguez, Fernando; Kramer, Susanne; Allers, Carolina; Simon, Valeska; Palisson, Francis; Gonzalez, Sergio; Yubero, Maria J.
    In animal models it has been shown that mesenchymal stromal cells (MSC) contribute to skin regeneration and accelerate wound healing. We evaluated whether allogeneic MSC administration resulted in an improvement in the skin of two patients with recessive dystrophic epidermolysis bullosa (RDEB; OMIM 226600). Patients had absent type VII collagen immunohistofluorescence and since birth had suffered severe blistering and wounds that heal with scarring. Vehicle or 0.5x10
  • Thumbnail Image
    Item
    Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep
    (INT PEDIATRIC RESEARCH FOUNDATION, INC, 2008) Herrera, Emilio A.; Ebensperger, German; Krause, Bernardo J.; Riquelme, Raquel A.; Reyes, Roberto V.; Capetillo, Maria; Gonzalez, Sergio; Parer, Julian T.; Llanos, Anibal J.
    Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small Pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates.
  • No Thumbnail Available
    Item
    Understanding current therapies in metastatic melanoma
    (SOC MEDICA SANTIAGO, 2016) Rodriguez, Rocio; Para, Angela; Gonzalez, Sergio; Molgo, Montserrat; Droppelmann, Nicolas; Acevedo, Francisco; Pena, Jose; Uribe, Pablo
    Cutaneous melanoma is a highly aggressive tumor developing from melanocytes, its incidence is increasing, and prognosis in advanced stages is daunting. New therapies have been approved during the recent years with unprecedented results, including inhibitors of MAPK/ERK pathway and immune checkpoint blockade (anti-cytotoxic T lymphocyte antigen- 4 (CTLA-4) as ipilimumab, anti-programmed cell death protein 1 (PD-L1) as pembrolizumab and anti-programmed cell death protein 1 ligand (PD-L1), among many others). The aim of this paper is to review currently available metastatic melanoma therapies focusing mainly on new therapies that have demonstrated effectiveness, after several decades of little progress in the treatment of this disease.