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Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.
Assuntos
Infecções por Escherichia coli , Probióticos , Animais , Bifidobacterium/fisiologia , Bifidobacterium longum subspecies infantis/metabolismo , Células CACO-2 , Citocinas/metabolismo , Escherichia coli/metabolismo , Humanos , Lactente , Camundongos , Probióticos/farmacologia , SuínosRESUMO
Regulated cell death is a physiological process that controls organismal homeostasis. Deregulation of cell death can lead to the development of a number of human diseases and tissue damage. Apoptosis is a best-known model of caspase-dependent regulated cell death, but recently necroptosis has garnered a lot of attention as a form of regulated cell death not mediated by caspases. Different stimuli can trigger necroptosis, and all of them converge at the activation of the protein kinase RIP3 (receptor-interacting protein 3) and the pseudokinase MLKL (mixed lineage kinase domain-like). Necroptosis activation relies on the unique protein-interaction motif RHIM (RIP homology interaction motif). Different RHIM-containing proteins (RIP1, DAI and TRIF) transduce necroptotic signals from the cell death trigger to the cell death mediators RIP3-MLKL. RIP1 has a particularly important and complex role in necroptotic cell death regulation ranging from cell death activation to inhibition, often in a cell type and context dependent fashion.
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Morte Celular , Animais , Humanos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de SinaisRESUMO
The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.
Assuntos
Anemia/fisiopatologia , Nível de Saúde , Síndromes Mielodisplásicas/fisiopatologia , Qualidade de Vida , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Transfusão de Sangue , Estudos de Coortes , Ecocardiografia , Feminino , Seguimentos , Coração/diagnóstico por imagem , Hemoglobinas/metabolismo , Humanos , Masculino , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Estudos Prospectivos , Inquéritos e Questionários , Velocidade de Caminhada/fisiologiaRESUMO
INTRODUCTION: Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. OBJECTIVE: We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. METHODS: Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. RESULTS: According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. CONCLUSION: This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects.
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Ácido Aminolevulínico/análogos & derivados , Ceratose Actínica/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Luz Solar , Ácido Aminolevulínico/efeitos adversos , Ácido Aminolevulínico/uso terapêutico , Protocolos Clínicos , Humanos , Seleção de Pacientes , Fotoquimioterapia/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos , Portugal , Espanha , Luz Solar/efeitos adversos , Protetores Solares/uso terapêutico , Temperatura , Resultado do TratamentoRESUMO
INTRODUCTION: Dental implant osseointegration can be impaired in medical conditions with low bone mass, such as glucocorticoid-induced osteoporosis. Intermittent human parathyroid hormone (PTH) [1-34] administration has shown relevant anabolic bone activity in various animal models of osteoporosis. Therefore, we studied the effects of intermittent PTH [1-34] on bone response around titanium implants in experimental osteoporosis induced by ovariectomy and glucocorticoid administration. METHODS: Titanium dental implants were placed in the proximal tibia metaphysis in 38 animals. Twenty-eight rabbits had undergone bilateral ovariectomy and further methylprednisolone administration for 4 weeks to induce osteoporosis. Ten healthy rabbits were used as controls. At week 8, osteoporotic rabbits started saline vehicle or intermittent PTH administration for 12 weeks. Bone mineral density (BMD) was assessed in peri-implant area, lumbar spine, and global and subchondral knee bone at baseline, and weeks 6 and 20. Animal sacrifice was carried out at week 21. Afterward, tibiae were removed for µCT morphometry and undecalcified sections were evaluated by light and scanning electron microscopy. RESULTS: PTH increased bone-to-implant contact compared with control rabbits or vehicle administration in osteoporotic rabbits (P < 0.005). PTH-induced new bone formation around external and internal surfaces of titanium implants led to a significant increase of BMD at peri-implant area in osteoporotic rabbits at week 20, when compared with vehicle (P < 0.005). Likewise, PTH increased BMD in other analysed regions. CONCLUSIONS: Intermittent administration of PTH [1-34] enhances the bone response around titanium implants in a rabbit model of ovariectomy and glucocorticoid-induced osteoporosis.
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Densidade Óssea/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Glucocorticoides , Implantes Experimentais , Metilprednisolona , Osteoporose/etiologia , Ovariectomia , Coelhos , Propriedades de Superfície , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Titânio/química , Microtomografia por Raio-XRESUMO
BACKGROUND: The standard procedure for the diagnosis of central nervous system (CNS) infections consists of cerebrospinal fluid (CSF) sampling, which is usually accomplished by a lumbar puncture. However, in some patients presenting with acute hydrocephalus submitted to immediate CSF drainage, the fluid is customarily obtained from the placed draining system. In addition, the CSF obtained from the ventricular and lumbar spaces in some cases may show unusual differences, both in physiological and pathological conditions. ILLUSTRATIVE CASES: We report two children who presented with confounding results in the initial studies of their ventricular and lumbar CSF who were subsequently diagnosed with tuberculous meningitis, causing delay in diagnosis and treatment. AIM. By reporting these cases, we wanted to alert the treating physician about the possibility of this discrepancy to avoid the delayed diagnosis and management of the affected patients. DISCUSSION: We comment on the possible pathophysiological mechanisms that may result in this dissociation in ventricular and lumbar CSF composition. CONCLUSIONS; Normal results in CSF studies, especially those of the ventricular fluid, do not always rule out the presence of tuberculous meningitis. We suggest obtaining a CSF sample from the lumbar subarachnoid space in doubtful, or suspicious, cases of CNS infection even in the presence of a normal ventricular CSF.
Assuntos
Líquido Cefalorraquidiano , Hidrocefalia , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/complicações , Tuberculose Meníngea/diagnóstico , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/microbiologia , Feminino , Humanos , Hidrocefalia/líquido cefalorraquidiano , Hidrocefalia/diagnóstico , Hidrocefalia/etiologia , Lactente , Masculino , Punção Espinal , Tomografia Computadorizada por Raios X , Tuberculose Meníngea/microbiologiaRESUMO
BACKGROUND: Methotrexate is a chemotherapeutic drug that is used in therapy of a wide variety of cancers. The efficiency of treatment with this drug is compromised by the appearance of resistance. Combination treatments of MTX with other drugs that could modulate the expression of genes involved in MTX resistance would be an adequate strategy to prevent the development of this resistance. METHODS: The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. A global comparison of all the studied cell lines was performed in order to find out differentially expressed genes in the majority of the MTX-resistant cells. S100A4 mRNA and protein levels were determined by RT-Real-Time PCR and Western blot, respectively. Functional validations of S100A4 were performed either by transfection of an expression vector for S100A4 or a siRNA against S100A4. Transfection of an expression vector encoding for beta-catenin was used to inquire for the possible transcriptional regulation of S100A4 through the Wnt pathway. RESULTS: S100A4 is overexpressed in five out of the seven MTX-resistant cell lines studied. Ectopic overexpression of this gene in HT29 sensitive cells augmented both the intracellular and extracellular S100A4 protein levels and caused desensitization toward MTX. siRNA against S100A4 decreased the levels of this protein and caused a chemosensitization in combined treatments with MTX. beta-catenin overexpression experiments support a possible involvement of the Wnt signaling pathway in S100A4 transcriptional regulation in HT29 cells. CONCLUSIONS: S100A4 is overexpressed in many MTX-resistant cells. S100A4 overexpression decreases the sensitivity of HT29 colon cancer human cells to MTX, whereas its knockdown causes chemosensitization toward MTX. Both approaches highlight a role for S100A4 in MTX resistance.
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Antimetabólitos Antineoplásicos/farmacologia , Neoplasias do Colo/metabolismo , Resistencia a Medicamentos Antineoplásicos , Metotrexato/farmacologia , Proteínas S100/metabolismo , Western Blotting , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Interferência de RNA , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/genética , Transcrição Gênica , Transfecção , Regulação para Cima , beta Catenina/genética , beta Catenina/metabolismoRESUMO
OBJECTIVE: To assess the effectiveness and safety of using 5-azacitidine to treat myelodysplastic syndromes. METHODS: Review of medical records of patients who received 5-azacitidine 75mg/m(2) subcutaneously for during 7 days every 28 days in twelve cycles as compassionate use. We evaluated the objective response, clinical improvement and time to disease progression. We recorded adverse reactions described in the medical history. RESULTS: Six patients were candidates for treatment with 5-azacitidine. Three cases were evaluated over the study period. Most remained in partial response or better after the study, and no longer needed transfusions. In one patient, the treatment appeared to delay progression to leukaemia. CONCLUSIONS: 5-Azacitidine might be considered an effective and relatively safe drug, and may have contributed to controlling peripheral cytopenias, improving the quality of life and delaying progression to leukaemia. Additional studies with more patients are needed to support these results.
Assuntos
Antimetabólitos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Anemia Refratária com Excesso de Blastos/terapia , Antimetabólitos/efeitos adversos , Azacitidina/efeitos adversos , Terapia Combinada , Ensaios de Uso Compassivo , Diarreia/induzido quimicamente , Progressão da Doença , Toxidermias/etiologia , Avaliação de Medicamentos , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Transfusão de Plaquetas , Qualidade de Vida , Proteínas Recombinantes , Estudos RetrospectivosRESUMO
Mesenteric cysts are rare tumors, they can emerge from any part of the mesentery of the bowel from the duodenum to the rectum. Their symptomatology can mimic almost any abdominal disease making diagnosis troublesome. In some circumstances, these cysts can grow to considerable sizes making resection almost impossible since its size can compromise different structures. Surgery is the treatment of choice as complete resection is the only curative treatment. We present a case of a female patient, she suffered from recurrent episodes of abdominal pain mistaken as gastritis. After a profound evaluation, a giant mass in her abdomen was identified and successfully treated. Giant primary mesenteric cyst was the final diagnosis.
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OBJECTIVE: To identify the different types of cytostatic prescription errors in adult and paediatric oncohematological patients in our hospital and to propose strategies for improvement. METHODS: Longitudinal, prospective, observational study in which prescriptions for antineoplastics from the haematology and paediatric oncohaematology departments were validated over a 15-month period. The types of error were classified in accordance with the terminology and taxonomy published by Otero and cols in the document "Medication errors: standardisation of terminology and classification". Eleven variables were recorded. Amongst other parameters, the following were determined: percentage of overall error, percentage of error in type of prescription, percentage of service error, percentage of pharmaceutical intervention and level of acceptance. RESULTS: A total of 92 errors were recorded which corresponded to 1.4% of the total prescriptions. The most significant errors were: incorrect dose (28.2%), incorrect duration (21.7%), incorrect volume and/or inadequate vehicle (16.3%), and in one case a prescription was made up where the patient was allergic to the specific cytostatic drug prescribed. 81.8% of prescription errors were made manually. In the haematology department a 0.9% error was recorded, as was a 3.5% error in paediatric oncohaematology. Both the rate of pharmaceutical intervention and its level of acceptance were 100%.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Erros de Medicação/estatística & dados numéricos , Serviço de Farmácia Hospitalar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Some reports have documented posterior fossa cysts resulting in syringomyelic obstruction of cerebrospinal fluid (CSF) flow caused by cyst displacement within the foramen magnum. Rarely the syringomyelia is caused by acquired Chiari malformation due to a retrocerebellar arachnoid cyst. OBJECTIVE: To report the case of a 38-year-old man with hydrocephalus and syringomyelia, who was found to have a Chiari malformation secondary to a posterior fossa arachnoid cyst. After endoscopic third ventriculostomy, the patient was submitted to foramen magnum decompression and arachnoid cyst removal that were followed by resolution of both the Chiari malformation and the syringomyelia. DISCUSSION: In most published cases the syringomyelia has been attributed to obstruction of CSF flow at the foramen magnum by the arachnoid cyst itself. There is only one previous report of a posterior fossa arachnoid cyst producing tonsillar descent and syringomyelia. CONCLUSIONS: Posterior fossa arachnoid cysts can result in acquired Chiari malformation and syringomyelia. In our view, the management of these patients should be directed at decompressing the foramen magnum and include the removal of the walls of the coexistent arachnoid cyst as it seems to be the crucial factor that accounts for the development of the syringomyelia that these patients present.
Assuntos
Cistos Aracnóideos , Doenças Cerebelares/etiologia , Fossa Craniana Posterior , Hérnia/etiologia , Siringomielia/etiologia , Adolescente , Adulto , Cistos Aracnóideos/complicações , Cistos Aracnóideos/cirurgia , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/patologia , Criança , Fossa Craniana Posterior/patologia , Fossa Craniana Posterior/cirurgia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Literatura de Revisão como AssuntoRESUMO
BACKGROUND: Spinal cord rethetering can occur after the primary surgical repair of myelomeningoceles (MMC) and lipomeningoceles (LMC) and produce devastating physical and psychological consequences. The inadvertent introduction of skin elements at the time of the initial surgery can lead to the growth of intraspinal epidermoid or dermoid cysts. OBJECTIVES: To review the incidence of spinal cord tethering following surgery for open and occult spinal dysraphism and to analyze factors that might influence the appearance of this complication. We also aimed to search technical measures at the time of the primary operation that might prevent the occurrence of symptomatic cord retethering. MATERIAL AND METHODS: We reviewed the medical records of patients submitted to surgical repair of MMC (n=162) or occult spinal dysraphism (n= 54) during the period 1975-2005 who developed symptomatic tethered cord syndrome. RESULTS: Eleven of 162 (6.79%) patients with MMC and 2 of 54 (3.7%) with LMC developed clinical symptoms and signs of spinal cord tethering after intervals ranging from 2 to 37 years after the initial surgical repair of their back lesions. Indications for surgical re-exploration were based mainly on clinical grounds. Postoperative fibrosis was a constant finding in all instances. Other surgical findings included inclusion tumors of cutaneous origin (n=3), lumbar canal stenosis (n= 2), foreign body reactions (n= 2), residual lipoma (n= 1), and a tight hyalinized filum (n=1). Interestingly, 3 of 162 (or 1.85%) myelomeningoceles were found to harbor an intradural epidermoid tumor at the time of spinal cord dethetering, accounting for an incidence of cutaneous inclusion tumors of 27% in cases of post- MMC repair tethering. After a mean follow-up time of 5.5 years, eight patients were improved, two were unchanged and one was worsened. CONCLUSIONS: Neurological deterioration is not a necessary consequence of the natural history of patients with MMC or LMC. Early or late clinical deterioration can be due to spinal cord re-tethering and deserves timely investigation and surgical exploration. Results of surgical intervention were rewarding as 92% of the patients showed improvement or stabilization in their otherwise deteriorating condition. We also report two infrequent causes of spinal cord deterioration: lumbar canal stenosis and intense foreign-body reactions to implanted materials.
Assuntos
Meningomielocele/cirurgia , Reoperação , Medula Espinal/cirurgia , Disrafismo Espinal/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Região Lombossacral , Imageamento por Ressonância Magnética , Masculino , Meningomielocele/epidemiologia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Proper regulation of cell death signaling is crucial for the maintenance of homeostasis and prevention of disease. A caspase-independent regulated form of cell death called necroptosis is rapidly emerging as an important mediator of a number of human pathologies including inflammatory bowel disease and ischemia-reperfusion organ injury. Activation of necroptotic signaling through TNF signaling or organ injury leads to the activation of kinases receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) and culminates in inflammatory cell death. We found that, in addition to phosphorylation, necroptotic cell death is regulated by ubiquitination of RIP1 in the necrosome. Necroptotic RIP1 ubiquitination requires RIP1 kinase activity, but not necroptotic mediators RIP3 and MLKL (mixed lineage kinase-like). Using immunoaffinity enrichment and mass spectrometry, we profiled numerous ubiquitination events on RIP1 that are triggered during necroptotic signaling. Mutation of a necroptosis-related ubiquitination site on RIP1 reduced necroptotic cell death and RIP1 ubiquitination and phosphorylation, and disrupted the assembly of RIP1 and RIP3 in the necrosome, suggesting that necroptotic RIP1 ubiquitination is important for maintaining RIP1 kinase activity in the necrosome complex. We also observed RIP1 ubiquitination in injured kidneys consistent with a physiological role of RIP1 ubiquitination in ischemia-reperfusion disease. Taken together, these data reveal that coordinated and interdependent RIP1 phosphorylation and ubiquitination within the necroptotic complex regulate necroptotic signaling and cell death.
Assuntos
Apoptose , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sistemas CRISPR-Cas/genética , Linhagem Celular , Creatinina/sangue , Células HEK293 , Células HT29 , Humanos , Nefropatias/etiologia , Nefropatias/metabolismo , Camundongos , Complexo de Proteínas Formadoras de Poros Nucleares/deficiência , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Oligopeptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Quinases/metabolismo , Estrutura Terciária de Proteína , Proteínas de Ligação a RNA/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Ubiquitinação/efeitos dos fármacosRESUMO
PURPOSE OF INVESTIGATION: To determine the prevalence of human papillomavirus (HPV) using polymerase chain reaction (PCR) in women with abnormal cytology results. METHODS: A prospective study of 215 women with abnormal cytology results referred consecutively to the cervical pathology clinic was carried out. A second cervical cytology using the Bethesda System was performed on all the patients to confirm the initial diagnosis, as well as to test for the presence of HPV by PCR and a colposcopy and punch biopsy in cases presenting with an abnormal pattern on colposcopy. The sensivitiy, specificity, and positive and negative predictive value (PPV and NPV) were calculated using 2 x 2 tables. RESULTS: The women aged 35 years or younger presented a higher percentage of HPV infection (85.6%) than the women over 35 years of age (54%). The highest percentage of women with a positive result for HPV was found in those with a cytological high-grade squamous intraepithelial lesion (HSIL) (85.5%), as compared with 47.4% of the women with a cytological low-grade squamous intraepithelial lesion (LSIL). HPV infection has a high negative predictive value (93.2% of cases) and a high sensitivity (93.5%) for the detection of HSIL by biopsy, although the specificity and positive predictive value were low, 51.5% and 52.1%, respectively. CONCLUSION: Patients with cytological HSIL have a high prevalence of HPV infection.
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Colo do Útero/citologia , Colo do Útero/virologia , Neoplasias de Células Escamosas/epidemiologia , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Idoso , Biópsia/métodos , Colposcopia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Sensibilidade e Especificidade , Espanha/epidemiologia , Esfregaço Vaginal/métodosRESUMO
We report a patient, given a ventriculoperitoneal shunt at the neonatal period, who presented with a painless subcutaneous mass on his neck. Plain radiographs of the cervical region showed that the swelling was made up by a migrated and coiled peritoneal catheter. We briefly discuss the proposed mechanism for this complication and suggest that this occurrence must be taken into account at the time of evaluating a patient with shunt malfunction.
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Pescoço/patologia , Derivação Ventriculoperitoneal/instrumentação , Adulto , Diagnóstico Diferencial , Falha de Equipamento , Humanos , Masculino , Derivação Ventriculoperitoneal/efeitos adversosRESUMO
Overdrainage in ventricular shunting constitutes a difficult to prevent and to treat complication. The authors reviewed a retrospective series of 512 children submitted to a ventricular shunting procedure aimed at analysing factors influencing this type of complication. The causes for the hydrocephalus were congenital (n=172), post-myelomeningocele (n=123), posthemorrhagic (n=103), tumoral (n=64), postmeningitis (n=40) and posttraumatic (n=10). Eighty-eight children (17.8%) evolved with a complication related to the excessive function of the valve. The authors investigated the relationship between hydrocephalus' etiology and type of overdrainage syndromes. The most frequent complication was ventricular catheter block (n=50), followed by symptomatic slit ventricle syndrome (SVS) (n=19), subdural hematoma (n=10) and trapped fourth ventricle (n=9). There were no statistical differences regarding complications for each etiologic subset of hydrocephalus. SVS occurred in 19 children (3.71%), a low rate according to the current literature. Posthemorrhagic and postinfectious hydrocephalus grouped together showed a higher rate of SVS (p=0.005), a feature that we attributed to the cerebral destruction caused by these two conditions. Treatment of SVS was complex and required diverse procedures, applied in an escalated way, which included five decompressive craniectomies. The authors suggest avoiding, as much as possible, the use of ventricular shunts, and recommend the alternative use of new technology valves and neuroendoscopic procedures.
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Derivações do Líquido Cefalorraquidiano/efeitos adversos , Hidrocefalia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Hidrocefalia/diagnóstico por imagem , Hidrocefalia/patologia , Incidência , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Complicações Pós-Operatórias/classificação , Estudos Retrospectivos , Síndrome , Tomografia Computadorizada por Raios XRESUMO
Necroptosis is a caspase-independent regulated type of cell death that relies on receptor-interacting protein kinases RIP1 (receptor-interacting protein kinases 1) and RIP3. Tumor necrosis factor-α (TNFα)-stimulated assembly of the TNFR1 (TNF receptor 1)-associated signaling complex leads to the recruitment of RIP1, whose ubiquitination is mediated by the cellular inhibitors of apoptosis (c-IAPs). Translocation of RIP1 to the cytoplasm and association of RIP1 with the necrosome is believed to correlate with deubiquitination of RIP1. However, we found that RIP1 is ubiquitinated with K63 and linear polyubiquitin chains during TNFα, IAP antagonist BV6 and caspase inhibitor zVAD-fmk-induced necroptotic signaling. Furthermore, ubiquitinated RIP1 is associated with the necrosome, and RIP1 ubiquitination in the necrosome coincides with RIP3 phosphorylation. Both cellular IAPs and LUBAC (linear ubiquitin chain assembly complex) modulate RIP1 ubiquitination in IAP antagonist-treated necrotic cells, but they use different mechanisms. c-IAP1 regulates RIP1 recruitment to the necrosome without directly affecting RIP1 ubiquitination, whereas HOIP and HOIL1 mediate linear ubiquitination of RIP1 in the necrosome, but are not essential for necrosome formation. Knockdown of the E3 ligase c-IAP1 decreased RIP1 ubiquitination, necrosome assembly and necroptosis induced by TNFα, BV6 and zVAD-fmk. c-IAP1 deficiency likely decreases necroptotic cell death through the activation of the noncanonical NF-κB pathway and consequent c-IAP2 upregulation. The ability to upregulate c-IAP2 could determine whether c-IAP1 absence will have a positive or negative impact on TNFα-induced necroptotic cell death and necrosome formation. Collectively, these results reveal unexpected complexity of the roles of IAP proteins, IAP antagonists and LUBAC in the regulation of necrosome assembly.
Assuntos
Proteínas Inibidoras de Apoptose/genética , Necrose/patologia , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Ubiquitina-Proteína Ligases/genética , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/fisiologia , Proteína 3 com Repetições IAP de Baculovírus , Inibidores de Caspase/farmacologia , Linhagem Celular Tumoral , Células HT29 , Humanos , Proteínas Inibidoras de Apoptose/biossíntese , Proteínas Inibidoras de Apoptose/metabolismo , Células L , Camundongos , NF-kappa B/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fatores de Transcrição , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitina/química , Ubiquitina-Proteína Ligases/biossíntese , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND: Herpesvirus-like DNA sequences have been found in lesions from patients with Kaposi's sarcoma in its several forms, suggesting that this tumor may be caused by a new herpesvirus, referred to as Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8. METHODS: We analyzed DNA from skin and lung lesions, healthy skin, and peripheral blood mononuclear cells of three heart transplant recipients with Kaposi's sarcoma. We also studied DNA from normal skin and from peripheral blood of Kaposi's sarcoma-free heart transplant recipients. Samples were analyzed by polymerase chain reaction with specific primers to amplify the KS 330 sequence. RESULTS: The KS 330 fragment was found in Kaposi's sarcoma tissue of all three patients, in normal skin of one of them, and in peripheral blood of two. It was not detected in any of the samples from skin or peripheral blood of heart transplant recipients not affected by Kaposi's sarcoma. DNA extracted from a peripheral blood sample of one patient before transplantation showed that the KS 330 sequence was already detectable at that time. CONCLUSIONS: These findings suggest that Kaposi's sarcoma-associated herpesvirus may play a significant role in the pathogenesis of all forms of Kaposi's sarcoma. The development of the tumor in transplant recipients may be related, at least in some cases, to transplantation-associated immunosuppression, rather than to the acquisition of the virus from the donor.
Assuntos
Transplante de Coração , Herpesvirus Humano 8/isolamento & purificação , Neoplasias Pulmonares/virologia , Sarcoma de Kaposi/virologia , Neoplasias Cutâneas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias , Sarcoma de Kaposi/terapiaRESUMO
Atretic cephalocele appears as an unimportant and benign lesion. This malformation consists of meningeal and vestigial tissues (arachnoid, glial, or central nervous system rests). The authors report the findings in 16 cases (seven parietal and nine occipital) of rudimentary cephaloceles. Twelve patients presented with associated brain abnormalities detected by either computerized tomography (CT) or magnetic resonance imaging (MR). Nine lesions also exhibited an anomalous vascular component demonstrated by CT or MR imaging or at surgery. The existence of this tiny malformation in five cases was the main diagnostic clue to a severe complex of cerebral anomalies, namely cerebro-oculomuscular (Walker-Warburg) syndrome. An occipital location of the atretic cephalocele was associated with the worst prognosis, with only two children developing normally. However, a parietal location carried a better prognosis, which is contrary to the outcome reported in the current literature. The authors classify atretic cephaloceles into two types based on histological examination of the surgical specimens, and suggest that these types represent different stages in the development of this malformation. It is concluded that, in the evaluation of the atretic cephalocele, the neurosurgeon is obliged to proceed to a detailed neuroradiological study of the patient and that the prognosis does not depend on the existence of the cephalocele itself, but rather on associated "occult" brain anomalies.