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Trismus refers to restriction in the ability to open the mouth. Comprehensive evaluation of trismus and its treatment outcomes needs a multidimensional, self-administered, trismus specific tool. In the present scenario, Gothenburg trismus questionnaire is the only reliable instrument to quantify trismus. Translation of this questionnaire helps in providing standardized documentation of trismus related problems and to obtain a patient's perspective on treatment outcomes within various populations. The aim of this study was to translate the Gothenburg trismus questionnaire-2 (GTQ 2) into Telugu (one of the Indian Languages) and validation of the translation for its effective use in regional Telugu speaking patients. The GTQ 2 was translated according to the guidelines framed by the International Society for Pharmacoeconomics and Outcomes Research: (1) forward translation, (2) reconciliation and back translation, (3) cognitive debriefing, and (4) pilot testing. The psychometric properties of the translated version were evaluated by testing its internal consistency, construct validity, known-group validity and floor and ceiling effects. Patients who reported with or without trismus to the Head and Neck Oncology outpatient clinic were enrolled for the study. Comparison of the GTQ scores was done using Mann-Whitney U-test. The Pearson correlation coefficient was used for assessing convergent and divergent validity. Internal Consistency was calculated using Cronbach's alpha coefficient. The translated version of the GTQ 2 was administered to 60 patients (30 trismus patients and 30 non-trismus patients). GTQ 2 was successfully translated without any significant issues. Construct validity of the translated version was confirmed and it has a good internal consistency (α > 0.7). The translated instrument can differentiate between those with and without trismus (p < 0.0005). A valid and reliable Telugu version of the Gothenburg Trismus Questionnaire-2 is now available for the benefit of Indian patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-021-01369-7.
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Surgeons treating advanced carcinoma of the tongue with total glossectomy face many conflicts in view of the morbidity and poor functional and survival outcomes following surgery. It is pertinent to study the patients undergoing total tongue compartment resection as a separate cohort to analyse their outcomes. This study investigated the oncological outcomes of 150 patients with advanced tongue squamous cell carcinoma who underwent total glossectomy. The results suggest that compartment resection significantly improved local control, irrespective of margin status. The presence of multiple positive nodes was found to be an independent poor prognostic factor, and adjuvant radiation significantly improved survival. Total glossectomy is feasible and safe in both the primary and salvage setting and should be considered as the surgical option for advanced tongue cancer.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Carcinoma de Células Escamosas/cirurgia , Glossectomia , Humanos , Estudos Retrospectivos , Terapia de Salvação , Língua , Neoplasias da Língua/cirurgiaRESUMO
Dermal metastasis (DM) is, by definition, the involvement of the skin by cancer cells that originate from cancer elsewhere in the body. The skin is considered a rare site of distant failure in head and neck cancer and DM is the bearer of a poor outcome. Literature about it is limited so this study was undertaken to analyse the factors associated with its incidence and outcomes. A prospectively maintained database on operated cases of oral cancer at a tertiary cancer centre was analysed, and patients who developed dermal metastases during follow up were evaluated. Factors that contributed to early DM and predicted survival after its development were studied. A total of 68 patients (2.8%) had DM as the first presentation of recurrence after a median disease-free period of five months. Early DM was significantly associated with skin involvement by the primary tumour at the time of presentation (p=0.06), extracapsular extension of nodes (p=0.004), and with those who required adjuvant chemotherapy in view of aggressive histology (p=0.021). Median (range) survival after the detection of DM was 97 (5-328) days (3.25 months). Surgical excision of isolated cases was associated with significantly increased survival after detection (p=0.05). Whenever it is feasible without too much morbidity, solitary DM should be excised.
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Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Quimioterapia Adjuvante , Estudos de Coortes , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
[This corrects the article DOI: 10.1007/s13193-021-01369-7.].
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Malignant schwannoma, also called malignant peripheral nerve sheath tumor (MPNST), is a rare and aggressive tumor arising from the nerve sheath. We describe a rare case of endotracheal malignant peripheral nerve sheath tumor occurring in a middle-aged male who presented with asthma-like symptoms for 6 months with progressively increasing dyspnea. A computed tomogram (CT) scan of the thorax revealed near complete luminal obstruction of the trachea by a mass lesion at the level of the second and third tracheal rings. Microlaryngotracheoscopy revealed a fleshy pedunculated growth arising from the left side of the second and third tracheal rings and obliterating almost the entire tracheal lumen. Intraluminal complete excision of the mass was done. Later, he underwent excision of the 2nd and 3rd rings after the histopathology revealed MPNST. Patient after 28 months of follow-up is free of disease.
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BACKGROUND: Reconstruction is an integral part of the surgical management of oral cancer. Local flaps are one of the options in reconstruction of small to moderate sized defects of oral cavity. Reconstruction is an integral part of the surgical management of oral cancer. Every defect needs to be assessed individually to tailor made the reconstruction because of its multidimensionality and complexity. Varieties of autologous tissues are being used in reconstruction like local, regional, or free flaps which can be simple or complex tissues. There is always a trend to identify the newer flaps/technique to personalize reconstruction. Local flaps are also one of the options in reconstruction of small to moderate sized defects of oral cavity. Local tissue if it is available is in the primary surgeon's purview and the flap can be raised without much technical difficulty and morbidity. We used perforator based tissue from the face and neck which is richly supplied by the facial vessels and named as the Cervicofacial- Facial Artery Myocutaneous flap (C-FAM flap) for reconstruction of oral cavity. METHODS: We used perforator based local tissue from the face and neck which is supplied by facial vessels and named it as the C-FAM flap for the reconstruction of oral cavity defects. RESULTS: Twenty-eight patients underwent C-FAM flap reconstruction in different subsites of the oral cavity with acceptable functional rehabilitation. There was no flap loss. CONCLUSION: The C-FAM flap is a robust flap, which is reliable, pliable, and rich in its vascularity. It has to be one of the armamentarium for the oral cavity reconstruction. C-FAM flap: A Novel flap in Oral cavity reconstruction.
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Boca/cirurgia , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Adulto , Idoso , Artérias , Face/irrigação sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Carcinoma de Células Escamosas/cirurgia , Secções Congeladas , Margens de Excisão , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Reoperação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Recidiva Local de Neoplasia/mortalidade , Reoperação/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Adulto JovemRESUMO
Objective: To examine the correlation between body fat percentage (BFP) and general obesity indexes, including body mass index (BMI), waist circumference (WC) and waist to hip ratio (WHR) and calculate the corresponding BFP cutoff values in the middle aged and old people in Guangzhou. The corresponding cut-point of optimal body fat percentage for Guangzhou older population. Methods: Based on the Guangzhou Biobank Cohort Study (GBCS), 3 490 relatively healthy Guangzhou residents aged ≥50 years were selected and were randomly divided into 2 groups. The equations between BFP and BMI, WC, WHR were set up with Curve fitting analysis in one group. The multiple regression analysis was undertaken to establish predictive equations between BFP and BMI, WC, WHR with stepwise model for adding gender, age, physical activity, drinking and smoking. Then, the optimal cut-points of BFP corresponding to BMI, WC and WHR to reflect the degree of obesity were calculated. The equations were then validated with another group. Results: BFP increased with the increase of WHR, WC and BMI. BMI was a better predictor of body fat percentage than WC and WHR. The final regression equation was BFP=(-23.47 -8.87×sex) +2.94× (BMI) - 0.024 × (BMI)2,the coefficient of determination was 0.805. Based on the equation, the BFP corresponding to overweight/obesity (24 kg/m2≤BMI<28 kg/m2) were 24.3% ≤BFP<31.1% in men and 33.2%≤BFP<40.0% in women, respectively. BMI had a better consistency with BFP in identify obesity compared with WC and WHR, obtained the area of ROC 0.909 in men and 0.919 in women respectively. The sensitivity and specificity were 70.3% and 85.5% in men; and 75.2% and 93.0% in women respectively. Conclusion: BFP has a better correlation with BMI. The study results indicated that BFP for middle aged and old males and females in Guangzhou corresponding to overweight/obesity (BMI≥24 kg/m2) were <24.0% and <33.0% respectively.
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Tecido Adiposo , Índice de Massa Corporal , Obesidade , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
OBJECTIVE: In this work, we aimed to study whether myocardial infarction associated transcript (MIAT) exerts a regulative effect on cardiac hypertrophy via acting as a miR-150 sponge. MATERIALS AND METHODS: Cardiac hypertrophy was induced using Angiotensin II (Ang II). MIAT and miR-150 expression were quantified using qRT-PCR. Rat heart-derived H9c2 cells were used as the in vitro model. Cardiac hypertrophic features were assessed by quantifying cardiac hypertrophic genes and measurement of cell surface, protein synthesis and total protein content. RESULTS: MIAT is significantly increased in Ang II induced cardiac hypertrophy in a mouse model and in H9c2 cells. MIAT siRNA substantially alleviated the Ang II induced upregulation of ANP, BNP and ß-MHC in H9c2 cells and markedly attenuated the Ang II induced increase of the cell surface area and the protein synthesis. MIAT overexpression in H9c2 cells significantly reduced the miR-150 expression. MIAT inhibition also partly restored the miR-150 levels under Ang II treatment. MiR-150 overexpression could attenuate the Ang II induced upregulation of hypertrophic marker genes and suppress the Ang II induced hypertrophic phenotypes of the cells. CONCLUSIONS: MIAT is significantly increased in Ang II induced cardiac hypertrophy and contributes to the pathological development. MIAT can suppress miR-150 expression in cardiomyocytes and miR-150 is a downstream effector of MIAT in the development of cardiac hypertrophy.
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Cardiomegalia , MicroRNAs , RNA Longo não Codificante , Angiotensina II/farmacologia , Animais , Camundongos , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , RatosRESUMO
OBJECTIVE: Carcinoma of tongue is associated with a high risk of occult metastasis and mortality despite early-stage detection and therapy; the critical tumor thickness at which this risk increases has been demonstrated as 4 mm or greater. There are no sufficient data in the published literature to evaluate the role of postoperative radiation therapy (PORT) in the treatment of pT1-T2 N0 oral tongue cancers with depth of invasion 4 mm or greater. STUDY DESIGN: Historical cohorts of patients with primary pT1-T2 N0 oral tongue cancer of depth of invasion 4 mm or greater treated surgically from January 2010 to December 2012 were included in the study, and negative margins on initial resection were filtered. Locoregional recurrence and death were analyzed among the patients who received PORT and those who did not. RESULTS: A total of 103 patients fulfilled the above-mentioned criteria, with 62 patients receiving PORT and 41 patients not receiving PORT; median period of follow-up was 41.3 months. Logistic and Cox regression models showed no significant difference in locoregional recurrences (P = .078) and survival (P = .339) between patients who received PORT and those who did not receive PORT. CONCLUSIONS: PORT did not influence survival of patients with stage I and stage II deep tongue cancers, with 4 mm or greater tumor invasion depth.
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Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Língua/radioterapia , Neoplasias da Língua/cirurgia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Língua/patologiaRESUMO
The critical tumor depth at which the risk of occult metastasis increases in tongue cancer has been demonstrated as ≥4-5 mm. Conventional T staging might not be an accurate predictor for survival in situations wherein infiltrative growth pattern is easily overlooked. Thus risk of death associated with increase in tumor depth per millimeter might be useful to understand patient's disease status during follow up. Historical cohorts of patients with pT1N0 and pT2N0 primary squamous cell carcinoma of tongue treated between January 2010 and December 2011 were selected and analyzed in univariate and multivariate cox-regression model to indicate the risk of death associated with an increase in each millimeter of tumor depth. The median period of follow up was 34 months. Total 67 patients fulfilled the above mentioned criteria, among them 11 patients died by the end of study period. The mean (SD) age of the patients studied was 49.7 (12.7) years and their age ranged from 21 to 74 years. Among these 66 % (n = 44) were males. In the univariate log-rank test, margin status (p = 0.016), t-stage (p = 0.018) and increased tumor depth (p < 0.0001) were risk factors for occurrence of death. When adjusted for other risk factors in the multivariate cox-regression model, per one unit increase of tumor depth (mm) there was 1.07 (95 % CI 0.95, 1.21) units increased risk of death. Depth of tumor with increase in each millimeter in tongue cancer appears to be associated with risk of death irrespective of regional lymphatic spread.
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INTRODUCTION: Postcricoid carcinoma in India, is seen especially in middle-aged females. Surgical treatment for postcricoid carcinoma has reduced because of increased organ-preserving nonsurgical strategies. Surgical intervention leads to morbidity in the form of laryngectomy. OBJECTIVES/HYPOTHESIS: To study the outcomes of nonsurgical management and to assess whether organ preservation is justified or if radical surgery should be the first line of management for T3 postcricoid carcinoma. STUDY DESIGN/METHODS: This retrospective study analyzed 59 patients with T3 postcricoid carcinoma who were treated with nonsurgical modality in the form of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). End points studied were locoregional control, disease-free survival (DFS), and overall survival. We also observed feeding tube and tracheostomy tube dependency. RESULTS: Locoregional control rate, DFS rate, and overall survival at the end of 2 years were 8.98%, 8.59%, and 15.71% respectively. Seventeen and 12 patients of the study population were dependent on nasogastric tube and tracheostomy tube, respectively, until their last follow-up. CONCLUSION: Results of organ preservation with radical RT or CCRT do not show promising outcomes in the locally advanced T3 carcinoma of postcricoid. Radical surgery with appropriate reconstruction and postoperative radiotherapy is probably better in terms of local control as well as overall survival. Proper preoperative counseling and postoperative rehabilitation of speech and stoma can improve the quality of life of T3 postcricoid carcinoma patients. LEVEL OF EVIDENCE: 4.
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Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cartilagem Cricoide , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/radioterapia , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Índia/epidemiologia , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , TraqueostomiaRESUMO
BACKGROUND: Mesial temporal sclerosis (MTS) is the most common cause of drug resistant epilepsy amenable for surgical treatment and seizure control. METHODS: This study analyzed the outcome of patients with MTS following anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH) over 10 years and correlated the electrophysiological and radiological factors with the post operative seizure outcome. RESULTS: Eighty seven patients were included in the study. Sixty seven (77.2%) patients had an Engel Class 1 outcome, 9 (11.4%) had Class 2 outcome. Engel's class 1 outcome was achieved in 89.9% at 1 year, while it reduced slightly to 81.9% at 2 years and 76.2% at 5 year follow up. Seventy seven (88.5%) patients had evidence of hippocampal sclerosis on histopathology. Dual pathology was observed in 19 of 77 specimens with hippocampal sclerosis, but did not influence the outcome. Factors associated with an unfavorable outcome included male gender (p=0.04), and a higher frequency of pre-operative seizures (p=0.005), whereas the presence of febrile seizures (p=0.048) and loss of hippocampal neurons in CA4 region on histopathology (p=0.040) were associated with favorable outcome. The effect of CA4 loss on outcome is probably influenced by neuronal loss in other subfields as well since isolated CA4 loss was rare. Abnormal post operative EEG at the end of 1 week was found to be a significant factor predicting unfavorable outcome (p=0.005). On multivariate analysis, the pre-operative seizure frequency was the only significant factor affecting outcome. CONCLUSIONS: The present study observed excellent seizure free outcome in a carefully selected cohort of patients with MTS with refractory epilepsy. The presence of dual pathology did not influence the outcome.
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Lobectomia Temporal Anterior/métodos , Epilepsia do Lobo Temporal/cirurgia , Hipocampo/patologia , Resultado do Tratamento , Adolescente , Adulto , Criança , Eletroencefalografia , Epilepsia do Lobo Temporal/complicações , Feminino , Seguimentos , Humanos , Filamentos Intermediários/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/metabolismo , Estudos Retrospectivos , Sinaptofisina/metabolismo , Esclerose Tuberosa/complicações , Adulto JovemRESUMO
OBJECTIVE: In view of the conflicting results of cognitive and behavioral consequences of PB, the present study was planned to analyze its efficacy, serial neuropsychological functions and its impact on psychosocial functioning in adults with epilepsy while on phenobarbitone (PB). METHODOLOGY: This prospective multi-centric study carried out across 4 centers in India included 75 adult patients of ≥18 years (M:F=52:23; age: 27.3 ± 8.5 years) with epilepsy who were prescribed phenobarbitone and underwent serial standardized neuropsychological assessment (NIMHANS battery for adults) at baseline, 1 month, 3 months, 6 months and 12 months. The demographic, seizure details and outcome measures were recorded. RESULTS: Of the 75 patients, 63 had completed clinical and neuropsychological assessment, i.e. visit 1 (baseline), visit 4 (6 months) and visit 5 (12 months). There was no deterioration rather an improvement during the follow visits in all the neuropsychological functions. The results indicate that 16 neuropsychological variables changed significantly, viz. mental speed (p<0.001), sustained attention (p<0.001), focused attention (p<0.002), planning (p<0.001), concept formation (p<0.05), set shifting (p<0.001), verbal learning (p<0.0001), verbal memory (p<0.0001), visual memory (p<0.0001) and intelligence (p<0.001). The scales measuring the outcome of psychosocial functioning significantly changed during follow up included happiness (p<0.002), Impact of Epilepsy on patient's life (p<0.02), A-B Neuropsychological Assessment (p<0.015), HADS anxiety (p<0.001) and emotional disorder (p<0.006). There was a significant reduction in seizure severity as measured by Liverpool Seizure Severity Scale (p<0.002) and seizure freedom was maintained. CONCLUSIONS: This study demonstrated that phenobarbitone is effective, well tolerated AED and do not have cognitive impairment over one year. There was variable but distinct improvement in cognition and psychosocial functioning, and effective seizure control could be one of the factor for it.
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Anticonvulsivantes/uso terapêutico , Cognição/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Fenobarbital/uso terapêutico , Adulto , Anticonvulsivantes/efeitos adversos , Epilepsia/fisiopatologia , Feminino , Humanos , Índia , Masculino , Testes Neuropsicológicos , Fenobarbital/efeitos adversos , Estudos Prospectivos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Convulsões/psicologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Hybrid Verrucous Carcinoma is an uncommon tumour wherein Verrucous Carcinoma (VC) is coexisting with conventional Squamous Cell Carcinoma (SCC) within same maternal field. The heterogeneous nature, infrequency of occurrence and the difficulties associated with diagnosis and management of this tumor is discussed through a retrospective study. Patients of primary hybrid VC treated from Jan 2010 to May 2013 at a tertiary institute were analyzed on multivariate cox regression model. During the above mentioned period; 37 patients of hybrid VC were reported; 18(48.6 %) were male and 19(51.3 %) were female. Age ranged between 33 years to 78 years. Median follow up period was 32 months. T stage status and Stage grouping was not statistically significant for mortality (p value: 0.338). In the multivariate cox-regression model, the presence of second primary oral cancer was significantly associated with mortality, adjusted HR; 23.10 (95 % CI: 1.73, 307.65) (p = 0.017). Tumour staging is often unreliable in predicting prognosis of hybrid VC, occurrence of second primary oral cancer and recurrence appears to be significant factors effecting prognosis.
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Neurolathyrism is past history in India since Lathyrus sativus (khesari dal) is no longer used as a staple. A consensus has evolved that khesari dal is harmless as part of a normal diet. L-ODAP (ß-N-oxalyl-l-α-diamino propionic acid) the neurotoxic amino acid, from this pulse, is detoxified in humans but not in animals but still no laboratory animal is susceptible to it under acceptable feeding regimens. L-ODAP is an activator of protein kinase C and consequential crucial downstream effects such as stabilization of hypoxia inducible factor-1 (HIF-1) could be extremely conducive to humans under a variety of situations. ODAP is gradually finding a place in several patents for this reason. Homoarginine the second amino acid from L. sativus can be a better substrate for endogenous generation of nitric oxide, a crucial signaling molecule associated with the cardiovasculature and control of hypertension. These features could make L. sativus a prized commodity as a functional food for the general cardiovasculature and overcome hypoxic events and is set to change the entire perception of this pulse and neurolathyrism.
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Latirismo/fisiopatologia , Lathyrus/toxicidade , Diamino Aminoácidos/toxicidade , Animais , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Índia/epidemiologia , Latirismo/epidemiologia , Proteína Quinase C/metabolismoRESUMO
INTRODUCTION: The clinical and MR imaging features of neurosyphilis are highly varied. In this study, we describe the spectrum of the imaging findings in patients with neurosyphilis. METHODS: The MR imaging observations of 35 patients diagnosed to have neurosyphilis on the basis of cerebrospinal fluid reactive for the Venereal Disease Research Laboratory test were reviewed. RESULTS: All the 35 patients, including four with human immunodeficiency virus coinfection, met the CDC diagnostic criteria for neurosyphilis. Patients were classified into three groups: (1) neuropsychiatric, (2) meningovascular, and (3) myelopathic, based on the dominant clinical manifestations. Fourteen patients with neuropsychiatric manifestations showed diffuse cerebral atrophy (14), parenchymal signal changes in the mesial temporal region (2) and temporal and basifrontal regions (1), infarcts (3), and nonspecific white matter changes (3). Eleven patients with meningovascular form showed infarcts (6), diffuse cerebral atrophy (3), signal changes in the mesial temporal region (3), sulcal exudates (1), progressive multifocal leukoencephalopathy (1), and a mass surrounding the carotid sheath (1). Spine imaging in ten patients with myelopathy showed long-segment signal changes (5), contrast enhancement (2), and dorsal column involvement (2). Three of these patients had normal spinal study. Six patients in the myelopathic group also underwent brain MRI that showed signal changes in the temporal region (2) and frontal region (1), multiple infarcts (1), and enhancing hypothalami (1). Three patients had normal study. CONCLUSION: MRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.
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Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Neurossífilis/patologia , Medula Espinal/patologia , Centros Médicos Acadêmicos , Adulto , Feminino , Humanos , Masculino , Fenótipo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Centros de Atenção TerciáriaRESUMO
ß-N-Oxalyl-L-α,ß-diaminopropionic acid (l-ODAP) an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor agonist activates protein kinase C in white leghorn chick brain. The current study focuses on the protein kinase C downstream signaling targets associated with L-ODAP excitotoxicity in SK-N-MC human neuroblastoma cells and white leghorn male chick (Gallus domesticus) brain extracts. L-ODAP treatment in SK-N-MC cells (1.5 mM) and chicks (0.5 mg/g body weight) results in a decreased expression and increased phosphorylation of phosphatidylehthanolamine-binding protein 1 (PEBP1) up to 4 h which however, returns to normal by 8 h. D-ODAP, the non-toxic enantiomer however, did not affect PEBP1 levels in either chick brain or SK-N-MC cells. Decreased PEBP1 expression correlated with subsequent activation of Raf-1, MEK and ERK signaling components of the mitogen-activated protein kinase cascade and nuclear translocation of hypoxia inducible factor-1α (HIF-1α) in chick brain nuclear extracts and SK-N-MC cells. SK-N-MC cells over-expressing PEBP1 inhibited nuclear translocation of HIF-1α when treated with l-ODAP, indicating that down-regulation of PEBP1 is responsible for HIF-1α stabilization and nuclear localization. Excitotoxicity of L-ODAP may thus be the result of phosphorylation and down-regulation of PEBP1, a crucial signaling protein regulating diverse signaling cascades. L-ODAP induced convulsions and seizures in chicks could be the result of a hypoxic insult to brain.
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Diamino Aminoácidos/fisiologia , Regulação para Baixo/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Proteína de Ligação a Fosfatidiletanolamina/antagonistas & inibidores , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Animais , Linhagem Celular Tumoral , Galinhas , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , RatosRESUMO
The low incidence of neurolathyrism, its absence in several communities traditionally consuming Lathyrus sativus and the likely benefits of its inclusion as part of a normal diet are reviewed. The metabolism/detoxification of ODAP which is unique to humans may be a crucial factor in this regard. The presence of homoarginine in the pulse which has received scant attention in the past could make this an invaluable pulse since it could contribute to a sustained generation of NO. NO is well recognized for its role in cardiovascular physiology and general well-being and thus a daily dietary intake of homoarginine through small quantities of L. sativus may be of advantage and deserves to be exploited. The detoxification of ODAP in humans could spotlight the pulse further for its non-neurotoxic attributes. Activation of PKC by ODAP adds a new dimension to explore its possible therapeutic potentials in areas such as Alzheimer's disease, hypoxia, and long term potentiation. These novel approaches to both ODAP and homoarginine might entirely change our perception of this poor man's pulse.
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Diamino Aminoácidos/toxicidade , Dieta , Homoarginina/análise , Inativação Metabólica , Animais , Fenômenos Fisiológicos Cardiovasculares , Genótipo , Humanos , Latirismo/induzido quimicamente , Lathyrus/químicaRESUMO
BACKGROUND: Post-concussion syndrome (PCS) associated with mild traumatic brain injury (MTBI) can cause long-lasting disabilities. Magnetic resonance imaging (MRI) evaluation in these patients may demonstrate structural lesions that correlate with functional deficits on neuropsychological testing. However, little is known about the significance of the relationship between structural lesions on MRI, functional deficits on neuropsychological evaluation and outcome in patients with MTBI. AIMS: To assess neuropsychological deficits and structural lesions on MRI in patients with PCS following MTBI, and to find correlation between these findings and PCS. SETTINGS AND DESIGN: Prospective, observational, cohort study in a tertiary hospital. MATERIALS AND METHODS: The study cohort included consecutive patients with MTBI (three months or more duration) and PCS. All the patients in the cohort had neuropsychological testing using the National Institute of Mental Health and Neurological Sciences Neuropsychological Battery for head injury and also MRI using T1, T2 and FLAIR sequences. Statistical analysis was done using Fisher's Exact test of significance. RESULTS: All the 20 patients evaluated had neuropsychological deficits. Eleven patients had lesions on MRI. Disturbances of sleep, behavior and memory and abnormalities in tests for mental speed were more frequent in patients with lesions on MRI, but were not statically significant (P = 0.08). Both the test modalities localized lesions predominantly to the frontal and temporal lobes. All the symptoms observed in the patients were associated with prefrontal dysfunction on neuropsychological testing. CONCLUSIONS: Prefrontal dysfunction is invariably associated with PCS following MTBI. Structural lesions on MRI may not always be present but when present may influence the degree or severity of the symptoms.