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OBJECTIVES: The main aim of this systematic review was to evaluate the prevalence and type of associated anomalies in fetuses with heterotaxy diagnosed prenatally on ultrasound; the perinatal outcome of these fetuses was also studied. METHODS: An electronic search of MEDLINE, EMBASE and CINAHL databases was performed. Only studies reporting the prenatal diagnosis of isomerism were included. Outcomes observed included associated cardiac and extracardiac anomalies, fetal arrhythmia, abnormal karyotype, type of surgical repair and perinatal mortality. The analysis was stratified according to the type of heterotaxy syndrome (left (LAI) or right (RAI) atrial isomerism). Meta-analyses of proportions were used to combine data. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. RESULTS: Sixteen studies (647 fetuses) were included in the analysis. Atrioventricular septal defect was the most common associated major cardiac anomaly found both in fetuses with LAI (pooled proportion (PP), 59.3% (95% CI, 44.0-73.7%)), with obstructive lesions of the right outflow tract occurring in 35.5% of these cases, and in fetuses with RAI (PP, 72.9% (95% CI, 60.4-83.7%)). Fetal arrhythmias occurred in 36.7% (95% CI, 26.9-47.2%) of cases with LAI and were mainly represented by complete atrioventricular block, while this finding was uncommon in cases with RAI (PP, 1.3% (95% CI, 0.2-3.2%)). Abnormal stomach and liver position were found, respectively, in 59.4% (95% CI, 38.1-79.0%) and 32.5% (95% CI, 11.9-57.6%) of cases with LAI, and in 54.5% (95% CI, 38.5-70.1%) and 45.9% (95% CI, 11.3-83.0%) of cases with RAI, while intestinal malrotation was detected in 14.2% (95% CI, 2.5-33.1%) of LAI and 27.1% (95% CI, 7.9-52.0%) of RAI cases. Hydrops developed in 11.8% (95% CI, 2.9-25.6%) of fetuses diagnosed prenatally with LAI. Biventricular repair was accomplished in 78.2% (95% CI, 64.3-89.4%) of cases with LAI, while univentricular repair or palliation was needed in 17.0% (95% CI, 9.7-25.9%); death during or after surgery occurred in 26.8% (95% CI, 4.6-58.7%) of LAI cases. Most children with RAI had univentricular repair and 27.8% (95% CI, 15.5-42.1%) died during or after surgery. CONCLUSIONS: Fetal heterotaxy is associated with a high prevalence of cardiac and extracardiac anomalies. Approximately one quarter of fetuses with heterotaxy died during or after surgery. Abnormal heart rhythm, especially heart block, is common in fetuses with LAI, while this finding is uncommon in RAI. Biventricular repair was common in LAI while univentricular repair was required in the majority of children affected by RAI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Comunicação Interventricular/diagnóstico por imagem , Síndrome de Heterotaxia/diagnóstico por imagem , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Procedimentos Cirúrgicos Vasculares , Feminino , Comunicação Interventricular/mortalidade , Comunicação Interventricular/cirurgia , Síndrome de Heterotaxia/mortalidade , Síndrome de Heterotaxia/cirurgia , Humanos , Recém-Nascido , Morte Perinatal , Gravidez , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: Following a previous report, an experiment was conducted to determine the effect of increasing level of dried stoned olives pomaces (DSOP) in the diet of lactating buffaloes on milk and mozzarella cheese yield and characteristics. METHODS: Sixteen pluriparous buffaloes distributed into two groups were fed an isoenergetic (0.9 milk forage unit/kg) and isoprotein (149 g/kg dry matter [DM] of crude protein) diet, with or without DSOP. Each animal received 17 kg DM/d. Samples of forages and concentrates were weekly collected and used for duplicate chemical analyses. Individual milk samples from each control were analyzed for chemical and coagulating parameters and daily production of mozzarella cheese was estimated. At the end of the trial, bulk milk of each group was processed to produce mozzarella cheese and chemical (fat, protein, ash, pH) composition, fatty acids composition, carotenoids and tocopherols content were determined. A sensory test was also performed. The oxidative stability was measured on mozzarella cheese and on governing liquid. RESULTS: No significant differences were observed, neither for milk yield and body condition score, nor for milk characteristics. The fat was higher (p<0.05) in mozzarella of DSOP fed group but, saturated fatty acids were lower and unsaturated higher (p<0.01). Furthermore, lower atherogenic (p<0.01), and thrombogenic (p<0.05) indices were found in mozzarella cheese of DSOP fed group. In addition, the administration of DSOP did not affect the mozzarella cheese oxidative stability and no negative effect was found in the sensory properties. CONCLUSION: No contraindications appeared for the inclusion of DSOP in the diet of lactating buffaloes. Besides, important effects on mozzarella cheese quality were obtained, such as a modification of fat content and attributes with an increment in the mono-unsaturated. Additionally, a lower saturated/unsaturated ratio and atherogenic and thrombogenic indices suggest an improvement of dietetic and nutritional characteristics of mozzarella cheese.
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BACKGROUND: Patients undergoing thyroidectomy often complain aerodigestive disorders. In a previous study we showed the associations between voice impairment and proximal acid reflux, swallowing impairment and Upper Esophageal Sphyncter (UES) incoordination and the decrease in UES pressure in thirty-six patients observed before and soon afterwards uncomplicated thyroidectomy. This study investigated the state of post-thyroidectomy esophageal motility changes and its associations with these disorders after 18-24 months. PATIENTS AND METHODS: The thirty-six patients prospectively recruited according to selection criteria (thyroid volume ≤60 ml, benign disease, age 18-65 years, previous neck surgery, thyroiditis, pre- or postoperative vocal cord palsy) underwent voice (VIS) and swallowing (SIS) impairment scores, esophageal manometry and pH monitoring once again. RESULTS: After 18-24 months, both VIS and SIS recovered (respectively: p=0,022; p=0,0001); UES pressure increased (p=0,0001) nearing the preoperative values. The persistence of swallowing complaints were associated with the persistence of esophageal incoordination (p=0,03); the association between voice impairment and proximal acid reflux was confirmed (p<0,001). CONCLUSIONS: Our study confirms that aerodigestive disorders after uncomplicated thyroidectomy, largely transient, are strictly connected with upper esophageal motility changes. In this viewpoint, the innervation of upper aerodigestive anatomical structures (larynx, pharynx, upper esophagus) and its variations should be focused.
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Transtornos de Deglutição/etiologia , Tireoidectomia/efeitos adversos , Distúrbios da Voz/etiologia , Adolescente , Adulto , Idoso , Transtornos da Motilidade Esofágica/etiologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
AIM: Postoperative ileus has been considered an inevitable consequence of abdominal surgery. The aim of the study was to investigate the efficacy of same treatments in resolving postoperative ileus in various surgical approaches. METHODS: A total of 360 patients underwent abdominal surgery, and was divided into four groups: videolaparoscopic cholecystectomy, laparotomic colo-rectal surgery, laparotomic Hartmann procedure, laparotomic gastric surgery. In each group, patients received different postoperative treatments: chewing gum, olive oil, both, and water. Each group was compared with a control group. RESULTS: In patients who underwent videolaparoscopic cholecystectomy, median postoperative first passage of flatus and stool in the water group was 10 and 34 hours, respectively (P=0.006, P=0.021) and significantly earlier than in the control group (median postoperative 24 and 72 hours). Postoperative stay for the water group was lower (median day 1, 3rd interquartile 2.5) compared with control (median day 3; 3rd interquartile 7.0, P=0.01). In patients who underwent gastric surgery, median postoperative first passage of stool in the olive oil and chewing gum group was 48 hours, significantly earlier than in the control (median postoperative hour 120, P=0.04). Median time to first passage of flatus and stool was also earlier in the other groups compared with the control group, though this difference was not significant. CONCLUSION: Chewing gum, olive oil or both do not induce a relevant reduction of ileus after surgery. Water may be a safe and inexpensive option in reducing ileus. (United States National Institutes of Health, www.clinicaltrial.gov, number NCT01869231).
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Colecistectomia Laparoscópica , Procedimentos Cirúrgicos do Sistema Digestório , Íleus/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Idoso , Goma de Mascar , Colo/cirurgia , Defecação , Ingestão de Alimentos , Feminino , Flatulência , Motilidade Gastrointestinal , Humanos , Íleus/fisiopatologia , Laparotomia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Óleos de Plantas/uso terapêutico , Complicações Pós-Operatórias/fisiopatologia , Recuperação de Função Fisiológica , Reto/cirurgia , Estômago/cirurgia , Água/administração & dosagemRESUMO
Endometriosis is a chronic disorder, clinically associated with chronic pelvic pain, dyspareunia, dysmenorrhea, and infertility. Its socio-economic impact is extensive, given the large number of affected women in reproductive age, its symptomatology (that interferes with normal social life and the patient's ability to work), and its frequent association with infertility. Nonetheless, the diagnosis of endometriosis is still difficult and late in the evolution of the disorder. The authors have used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria to make a systematic review of the literature of the last 28 years, seeking to identify potential biomarkers useful for a non-invasive diagnosis of endometriosis. The authors have highlighted more than 50 biomarkers in the studies included in the present report, but they have not succeeded in identifying a clinically useful non-invasive diagnostic biomarker or panel of biomarkers. More studies are needed before biomarkers can be introduced in clinical practice.
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Biomarcadores/análise , Endometriose/diagnóstico , Antígenos Glicosídicos Associados a Tumores/análise , Líquido Ascítico/química , Autoanticorpos/análise , Biomarcadores/sangue , Biomarcadores/urina , Antígeno Ca-125 , Citocinas/análise , Endométrio/química , Feminino , Hormônios/análise , Humanos , Contagem de LinfócitosRESUMO
Dried stoned olive pomace (DSOP) was administered to dairy water buffaloes, and their productive performance and milk composition were analysed. Sixteen pluriparous lactating buffaloes were divided into two uniform groups (control and experimental), taking into consideration the following parameters: milk production (2,192 and 2,102 kg) and duration of lactation (254 and 252 d) of the previous year, distance from calving (51 and 43 d), milk production (9.71 and 10.18 kg/d), body condition score (BCS) (6.44 and 6.31) and weight (617 and 653 kg) at the beginning of the trial. Both diets had the same formulation: second cut alfalfa hay 20%, corn silage 42%, concentrate 38% but the two concentrates differed in their formulation, the experimental one contained 15.50% of DSOP as fed. The employed DSOP showed high amounts of secoiridoids, such as 3,4-dihydroxyphenylethanol (3,4-DHPEA) (1.2 g/kg DM), 3,4-dihydroxyphenylethanol-elenolic acid di-aldehyde (3,4-DHPEA-EDA) (12.6 g/kg DM), p-hydroxyphenylethanol-elenolic acid di-aldehyde (p-HPEA-EDA) (5.6 g/kg DM) and lignans, which are known to be powerful bioactive compounds. The control diet had an energy-protein content of 0.86 Milk FU/kg DM and 143.3 g/kg DM of crude protein, whereas the experimental diet of 0.87 Milk FU/kg DM and 146.6 g/kg DM of crude protein. Each animal of the two groups received 17 kg DM/d and each buffalo of the experimental group, by way of the concentrate, ingested 1.05 kg DM/d of DSOP. The trial lasted 40 days. No significant difference was found between the BCS (6.41 and 6.53), live weight (625.93 and 662.50 kg) and milk production (9.69 and 10.08 kg/d) of the two groups, as was the case for fat, protein, lactose, pH and coagulating parameters of the two milks. The milk fat of the experimental group had a significantly higher content of total tocopherols (10.45 vs 8.60 µg/g, p<0.01) and retinol (3.17 vs 2.54 µg/g, p<0.01). The content of the reactive substances with tiobarbituric acid (TBARs) was significantly lower in the milk fat of the experimental group (12.09 vs 15.05 µg MDA/g, p<0.01). The acid content of the milk fat of the experimental group had a significantly higher content (p<0.05) of C18:0 and of C18:3ω6. LC-MS/MS analysis showed the presence of 3,4-DHPEA (36.0 µg/L) in the milk of the DSOP-fed buffaloes, while other phenols were not found. DSOP, in the quantity utilized, can be used in the feeding of the lactating buffalo; the dietetic-nutritional characteristics of the milk are improved due to a greater contribution of tocopherols, retinol and the presence of hydroxytyrosol.
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OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.
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Interleucina-18 , Receptor 3 Toll-Like , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neurotoxina Derivada de Eosinófilo/genética , Neurotoxina Derivada de Eosinófilo/metabolismo , Interleucina-18/metabolismo , Receptor 3 Toll-Like/metabolismo , Triptases , Fator de Crescimento Neural/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Histamina/metabolismo , Interleucina-13 , Serotonina/metabolismo , Proteína Catiônica de Eosinófilo/metabolismo , Eosinófilos , Antivirais/farmacologia , Antivirais/metabolismo , Interleucina-12/metabolismoRESUMO
The data used came from two trials undertaken under the same climatic conditions (spring-summer). In both trials pluriparious buffaloes were utilized similar in weight, body condition score, and milk production from the previous year. From the first trial the data used was from the sub-period 23-88 DIM provided by seven animals fed ad libitum with diet A (6.69 MJ/kg DM; 158.30 g/kg of crude protein) with a forage/concentrate ratio of 48/52. From the second trial the data used was from the sub-period 33-90 DIM provided by seven animals fed ad libitum with diet B (6.63 MJ/kg DM; 179.50 g/kg of crude protein) and by seven animals fed ad libitum with diet C (5.99 MJ/kg DM; 155.40 g/kg of crude protein), each of the diets had the same forage/concentrate ratio (53/47). A significant difference was found in milk production between group B and C (13.08 vs. 11.56 kg/d, p<0.05), an intermediate production (12.10 kg/d) was noted in group A. A significant difference was found between fat (76.58 vs. 69.24 g/kg, p<0.05), protein (46.14 vs. 43.16 g/kg, p<0.05) and casein (39.94 vs. 34.98 g/kg, p<0.05) of the milk of group B with respect to group A. The milk of group C gave fat values (71.80 g/kg), protein (45.52 g/kg) and casein (39.06 g/kg) statistically equal to those of group B. The milk of groups B and C, in respect to the milk of group A, gave values of K20 (1.77, 1.82 vs. 3.68 min, p<0.05), statistically lower and values of A30 (48.28, 47.27 vs. 40.64 mm, p<0.05) statistically higher. Two simple linear regressions were calculated where the independent variable (x) was the daily standardized milk production, the dependent variable (y) or the daily intake of net energy or crude protein. Equation 1) NE (MJ/d) = 74.4049+2.8308×kg of normalized milk; equation 2) CP (kg/d) = 1.4507+0.1085×kg of normalized milk, both the equations were significant (p<0.05) with determination coefficients of 0.58 and 0.50 respectively. For a production of normalized milk that varies from 9 to 13 kg, the respective energy-protein concentrations fluctuate from 6.09 to 6.78 MJ/kg DM and from 148.00 to 174.46 g/kg DM.
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The diagnosis of oral cavity and oropharyngeal tumors can be obtained through clinical examination and biopsy. CT and MRI can then be used to define the extension of the disease. The aim of this study was to define the accuracy of clinical and MRI T staging of oral cavity and base of the tongue tumors and correlate the results with pathological data. Mandibular involvement, in a subgroup of patients, was determined and sensitivity, specificity, accuracy and positive and negative predictive values were evaluated. Fifty-nine patients affected by squamous cell carcinoma and 1 case of adenoido-cystic carcinoma were examined by means of a superconductive MR unit, using SE T1, and fat-suppressed T2 weighted sequences before contrast medium infusion. SE T1 and T1 fat-suppressed sequences after gadolinium-DTPA infusion were used. T stage accuracy of both clinical examination and MRI were found to be respectively 62% (k 0.459) and 82% (k 0.775). The sensitivity, specificity and accuracy of MRI in the detection of mandibular involvement were 94.1%, 60% and 81.5%, while the positive and negative predictive values were 80% and 85.7%, respectively. The sensitivity, specificity and accuracy of clinical examination in the detection of mandibular involvement were 100%, 30% and 74.1%, while the positive and negative predictive values were 70.8% and 100%. In the present study, MRI was seen to be an adequate technique for the assessment of oral cavity malignancies, in the evaluation of depth invasion, presence and extension of mandibular involvement.
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Imageamento por Ressonância Magnética , Neoplasias Bucais/diagnóstico , Neoplasias da Língua/diagnóstico , Feminino , Humanos , Masculino , Boca/patologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Neoplasias da Língua/patologiaRESUMO
Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.
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Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Imageamento por Ressonância Magnética , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Intervalo Livre de Doença , Glioma/patologia , Glioma/cirurgia , Humanos , Pessoa de Meia-Idade , Período Pós-Operatório , Taxa de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: To assess the diagnostic accuracy of delayed enhanced phase in addition to portal enhanced phase in MDCT imaging for depicting peritoneal carcinomatosis (PC) implants in patients with ovarian cancer. PATIENTS AND METHODS: We retrospectively reviewed double-phase, portal enhanced phase (PEP) and delayed enhanced phase (DEP), MDCT-examinations of 40 patients with clinical suspicion of recurrent PC from histopathologically-proven ovarian cancer, previously treated with both cytoreductive surgery and adjuvant/neoadjuvant chemotherapy. Image assessment was performed by three independent blinded readers (2 experienced and 1 less-experienced radiologists) in 3 different reading sessions: PEP (set A), DEP (set B), and PVP + DEP (set C). All CT-images were qualitatively assessed on the basis of the location of the lesion (based on Sugarbaker scheme), presence (indicating a confidence level for the diagnosis of PC), size and pattern. Reference standard both for detection and exclusion of PC was the evaluation of double-phase MDCT exams performed by two experienced readers in consensus, knowing clinical and laboratoristic parameters as well as previous and subsequent imaging (follow-up minimum of 12 months). Sensitivity, specificity, PPV, NPV and diagnostic accuracy of each reader for each reading session were calculated and compared. A subgroup analysis based on lesion pattern was also performed. RESULTS: On a total of 507 abdominal-pelvic sites evaluated, PC was found in 182 regions (35.9%). When considering experienced radiologists, no statistically significant differences (p>0.05) were found between the different sets of images. The analysis by less-experienced radiologist showed lower statistical results, which significantly improved when both PEP and DEP were evaluated. In the subgroup analysis, DEP showed significantly higher statistical results in the case of micronodular patterns. CONCLUSIONS: Our results indicate that the CT-acquisition protocol in patients with ovarian cancer for tumor staging should be based on portal phase alone, with a significant radiation dose reduction, whereas the addition of delayed phase images is useful for less-experienced readers.
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Carcinoma/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/diagnóstico , Carcinoma/secundário , Feminino , Humanos , Neoplasias Peritoneais/secundário , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To investigate the role of apoptosis in acute quadriplegic myopathy. BACKGROUND: Acute quadriplegic myopathy is a muscular disease characterized by diffuse flaccid weakness occurring in patients with severe systemic illness and exposure to corticosteroids or neuroblocking agents. Myofiber atrophy and thick filament loss are the distinguishing pathologic features on muscle biopsy. Increased calpains expression and lysosomal and nonlysosomal proteolytic pathways have been claimed as possible pathogenic factors. Nevertheless, the mechanisms leading to myofiber atrophy and thick filament loss need further investigation. PATIENTS AND METHODS: The expression of ubiquitin and proapoptotic proteases as well as DNA fragmentation in muscle biopsies from three patients with acute quadriplegic myopathy were studied. RESULTS: All patients exhibited an important overexpression of caspases, calpain, cathepsin B, and ubiquitin, and the presence of numerous apoptotic nuclei in over 70% of myofibers. CONCLUSIONS: These data suggest that apoptosis mediated by proteolytic proteases may play a role in the pathogenesis of acute quadriplegic myopathy.
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Apoptose , Músculos/patologia , Doenças Musculares/patologia , Quadriplegia/patologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Microscopia Eletrônica , Músculos/ultraestruturaRESUMO
Two brothers with myopathic coenzyme Q10 (CoQ10) deficiency responded dramatically to CoQ10 supplementation. Muscle biopsies before therapy showed ragged-red fibers, lipid storage, and complex I + III and II + III deficiency. Approximately 30% of myofibers had multiple features of apoptosis. After 8 months of treatment, excessive lipid storage resolved, CoQ10 level normalized, mitochondrial enzymes increased, and proportion of fibers with TUNEL-positive nuclei decreased to 10%. The authors conclude that muscle CoQ10 deficiency can be corrected by supplementation of CoQ10, which appears to stimulate mitochondrial proliferation and to prevent apoptosis.
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Músculos/patologia , Doenças Musculares/tratamento farmacológico , Doenças Musculares/patologia , Ubiquinona/análogos & derivados , Ubiquinona/deficiência , Ubiquinona/uso terapêutico , Adolescente , Criança , Pré-Escolar , Coenzimas , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Músculos/ultraestrutura , FenótipoRESUMO
OBJECTIVE: To screen Italian patients with oculopharyngeal muscular dystrophy (OPMD) for GCG repeat expansions in the Poly(A) binding-protein 2 (PABP2) gene. BACKGROUND: Oculopharyngeal muscular dystrophy is an adult-onset autosomal dominant muscle disease linked to 14q11 pathologically characterized by unique 8.5 nm intranuclear filaments in skeletal muscle fibers. Short expansions of a (GCG)6 repeat located in exon 1 of the newly isolated PABP2 gene have been demonstrated in a large number of OPMD families. METHODS: We studied 18 patients diagnosed with OPMD. A muscle biopsy was performed in 16 patients. Screening for the pathologic expansion was performed on a PCR amplified DNA fragment encompassing the GCG repeat. RESULTS: Heterozygous (GCG)-repeat expansions were detected in 13 patients in association with (GCG)6 normal allele or (GCG)7 polymorphic allele. All the patients whose muscle biopsy showed typical 8.5 nm intranuclear filaments had a mutated PABP2 allele. Five patients with no intranuclear filaments were homozygous for the normal (GCG)6 allele. The pathologic expansion appeared to be stable with no variation among family members and between different tissues as blood and skeletal muscle in the same individual. CONCLUSIONS: These data 1) further confirm PABP2 gene analysis as a valuable tool in OPMD diagnosis; 2) indicate that PABP2 gene mutations are always present among Italian patients with morphologically proven OPMD, suggesting genetic homogeneity of the disease; and 3) strengthen the putative role of mutated PABP2 protein in filamentous inclusions accumulation.
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Proteínas de Ligação a DNA/genética , Distrofias Musculares/genética , Repetições de Trinucleotídeos , Adulto , Idade de Início , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Distrofias Musculares/patologia , Músculos Oculomotores , Músculos Faríngeos , Proteína II de Ligação a Poli(A)RESUMO
The MHC region on 6p harbors at least one susceptibility gene for multiple sclerosis (MS). Within this region, HLA-DM loci are of interest being involved in class II antigen processing. We investigated the association of HLA-DM polymorphisms with MS. Sixty-three patients with MS and 46 healthy controls from continental Italy were typed for HLA-DM polymorphisms and HLA-DRB1 alleles. Besides, among the donors characterized for the DM polymorphisms, we considered 6 MS patients previously studied for the fine specificity of their MBP-specific T lymphocyte lines (TLL). The frequencies of allelic variants at the DMA and DMB loci were similar between MS patients and controls, even when HLA-DRB1*1501 positive and negative donors were analyzed separately. Patients with predominant responses to different MBP epitopes did not differ for their HLA-DM haplotype while patients with predominant responses to the same MBP epitope could present different HLA-DM haplotypes. HLA-DM polymorphisms do not associate with MS and may not affect specific patterns of T cell responses to MBP.
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Antígenos HLA-D/genética , Antígenos de Histocompatibilidade Classe II , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Polimorfismo Genético/imunologia , Linfócitos T/imunologia , Adulto , Alelos , Epitopos/análise , Feminino , Frequência do Gene , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/etiologiaRESUMO
Pseudothrombocytosis and pseudoleukocytosis occurred in a patient with essential mixed cryoglobulinemia (EMC) and atypical cutaneous ulcers, when the blood cell counts were estimated by the Model S Plus Coulter Counter. The spurious cell counts were found in serum as well as in plasma and whole blood, so the involvement of fibrinogen in this phenomenon is questioned. When timed serial counts were performed on whole blood at room temperature the highest value of WBCs was detected one hour after sample collection and that of platelets occurred at 6 hours, when leukocytosis had disappeared. Possible explanations for this phenomenon are offered.
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Crioglobulinemia/complicações , Leucocitose/etiologia , Trombocitose/etiologia , Contagem de Células/métodos , Crioglobulinemia/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Cutânea/etiologiaRESUMO
Beta-2-microglobulin concentrations were determined in serum samples from 45 patients with benign and malignant monoclonal gammopathies. In the group of patients suffering from multiple myeloma or Waldenström macroglobulinemia the mean beta 2-microglobulin level was significantly higher than in the group with monoclonal gammopathy of undetermined significance. Values above 3 mg/L were highly indicative of a neoplastic process and were observed in all the Waldenström patients and in greater than 90% of myeloma patients. No significant correlation was noticed between beta 2-microglobulin and monoclonal protein levels in any of the groups examined.
Assuntos
Biomarcadores Tumorais/sangue , Paraproteinemias/sangue , Microglobulina beta-2/análise , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Proteínas do Mieloma/sangue , Macroglobulinemia de Waldenstrom/sangueRESUMO
Up to 40% of ischemic strokes have no known cause (cryptogenic). The prevalence of persistent foramen ovale (PFO) amongst patients with cryptogenic stroke (CS) is twice as high as that of the normal population, therefore suggesting a causal relationship between the two entities. However, PFO by itself is not sufficient to cause stroke, as an embolic source is needed. This source is often unknown, making the causal relationship between CS and PFO hard to demonstrate. The most frequent, although still seldom, identifiable cause of embolism in an otherwise cryptogenic stroke associated with PFO is a deep venous thrombosis (DVT) of the lower extremities. Here, we present a unique case of brachiocephalic venous DVT associated with PFO and ischemic stroke in a young patient. As the search for DVT in patients with PFO and stroke is often limited to the lower extremities, this case may suggest that an unspecified number of DVTs are overlooked. Our report lends support to paradoxical embolism as a mechanism of stroke in patients with PFO and does, at least in selected cases, suggest a more detailed search for DVT beyond the lower extremities.
RESUMO
Neuronal outgrowth is guided by both extrinsic and intrinsic factors, involving transcriptional regulation. The acetylation of histones and transcription factors, which facilitates promoter accessibility, ultimately promotes transcription, and depends on the balance between histone deacetylases (HDACs) and histone acetyltransferases (HATs) activities. However, a critical function for specific acetylation modifying enzymes in neuronal outgrowth has yet to be investigated. To address this issue, we have used an epigenetic approach to facilitate gene expression in neurons, by using specific HDAC inhibitors. Neurons treated with a combination of HDAC and transcription inhibitors display an acetylation and transcription-dependent increase in outgrowth and a reduction in growth cone collapse on both 'permissive' (poly-D-lysine, PDL) and 'non-permissive' substrates (myelin and chondroitin sulphate proteoglycans (CSPGs)). Next, we specifically show that the expression of the histone acetyltransferases CBP/p300 and P/CAF is repressed in neurons by inhibitory substrates, whereas it is triggered by HDAC inhibition on both permissive and inhibitory conditions. Gene silencing and gain of function experiments show that CBP/p300 and P/CAF are key players in neuronal outgrowth, acetylate histone H3 at K9-14 and the transcription factor p53, thereby initiating a pro-neuronal outgrowth transcriptional program. These findings contribute to the growing understanding of transcriptional regulation in neuronal outgrowth and may lay the molecular groundwork for the promotion of axonal regeneration after injury.