RESUMO
Costello syndrome (CS) is a rare multiple congenital anomaly disorder which is caused by germline mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homologue (HRAS) proto-oncogene. Experimental data suggest perturbing effects of the mutated protein on the functional and structural organization of networks of cerebral cortex and on the activity-dependent strengthening of synaptic transmission known as long term potentiation (LTP). In five patients with molecularly proven diagnosis of CS and in a group of 13 age-matched control subjects we investigated activity-dependent synaptic plasticity. To this end, we used a paired associative stimulation (PAS) protocol, in which left ulnar nerve stimuli were followed by transcranial magnetic stimulation (TMS) pulses to right cortical hand area, and recorded motor evoked potentials (MEPs) by single pulse TMS from left first dorsal interosseus (FDI) muscle before and after PAS. In 4 out of 5 CS patients and in a subgroup of nine control subjects we also evaluated the time course and the topographical specificity of PAS after-effects. In these two subgroups, MEPs were measured before, immediately after and 30 min after PAS in the left FDI and left abductor pollicis brevis (APB). While the PAS protocol led to a 65% increase of the FDI MEP amplitude in controls, the LTP-like phenomenon was significantly more pronounced in CS patients, with motor responses increased by 230%. In addition, CS patients showed a similar MEP increase in both muscles while control subjects showed a slight increase in APB and only immediately after PAS. We hypothesize that the extremely enhanced PAS after-effects could be due to the influence of HRAS activity on the susceptibility of synapses to undergo LTP.
Assuntos
Encéfalo/fisiologia , Síndrome de Costello/metabolismo , Plasticidade Neuronal/fisiologia , Adolescente , Estudos de Casos e Controles , Estimulação Elétrica , Feminino , Humanos , Masculino , Proto-Oncogene Mas , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.
Assuntos
Síndrome LEOPARD/diagnóstico , Síndrome de Noonan/diagnóstico , Transtornos da Percepção/diagnóstico , Transtornos da Visão/diagnóstico , Percepção Visual , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Percepção de Profundidade/genética , Feminino , Genótipo , Humanos , Síndrome LEOPARD/genética , Masculino , Síndrome de Noonan/genética , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/genética , Transtornos da Percepção/genética , Fenótipo , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteínas Proto-Oncogênicas c-raf/genética , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/genética , Proteína SOS1/genética , Transtornos da Visão/genética , Testes Visuais , Acuidade Visual/genética , Adulto JovemRESUMO
The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.
Assuntos
Leucomalácia Periventricular/diagnóstico , Leucomalácia Periventricular/fisiopatologia , Exame Neurológico/métodos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Atividade Motora/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Ultrassonografia/métodosRESUMO
OBJECTIVES: The authors present the case of an adolescent affected with refractory epilepsy due to a neonatal ischemic infarction of the right medial cerebral artery. Hemiplegic since the first months of life, she began presenting motor partial seizures associated with drop attacks at 4.5 years; these were initially well controlled by antiepileptic drugs, but at 10 years seizures appeared again and became refractory. Thus, at 14 years and 10 months, she was submitted to a right hemispherectomy that made her rapidly seizure free. In the post-surgical follow-up lasting 5 years, neuropsychological serial assessments showed an impressive progressive improvement of cognitive skills, namely, visuospatial abilities. This case seems to challenge the widely spread feeling that functional catch-up in brain-injured children could only occur early in life. In effect, the astonishing recovery especially of visuospatial skills in our case occurred in adolescence after a late surgical intervention of right hemispherectomy. METHODS: Different neuropsychological aspects are discussed. The reorganisation process recovered the spatial and linguistic abilities as well as the verbal and visuospatial memory; however, there was a persistent impairment of complex spatial and perceptual skills as well as recall abilities. Despite the deficit of complex visual stimuli processing, the patient showed a good performance in the recognition of unknown faces. CONCLUSIONS: Probably, the absence of seizures in the first 4 years of life could have allowed a generally adequate compensatory reorganisation, successively masked by the persistent and diffuse epileptic disorder. The seizure control produced by surgery eventually made evident the effectiveness of the brain reorganisation.
Assuntos
Dano Encefálico Crônico/cirurgia , Epilepsia Parcial Complexa/cirurgia , Hemisferectomia , Infarto da Artéria Cerebral Média/complicações , Plasticidade Neuronal/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Adolescente , Adulto , Ritmo alfa , Anticonvulsivantes/administração & dosagem , Dano Encefálico Crônico/etiologia , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Dominância Cerebral/fisiologia , Resistência a Medicamentos , Quimioterapia Combinada , Epilepsia Parcial Complexa/etiologia , Feminino , Seguimentos , Humanos , Lactente , Testes de Linguagem , Testes Neuropsicológicos , Recuperação de Função Fisiológica , Convulsões/fisiopatologia , Ritmo TetaRESUMO
Risk management of occupational exposure in hospital personnel involved in the preparation and administration of antineoplastic drugs was performed using the A.S.I.A. model. The first step was auditing of compliance. Training of workers specifically addressed the areas of deviation from guidelines. Medical surveillance, and risk assessment, were oriented toward observed deviations.
Assuntos
Antineoplásicos , Exposição Ocupacional/prevenção & controle , Saúde Ocupacional , Gestão de Riscos/métodos , Humanos , Modelos TeóricosRESUMO
Often in Occupational Medicine doctors misunderstand or underestimate the occupational psychologic discomfort forms deriving from "transverse risks" of organizational kind. In this communication is shortly described a our study with in a "call center". We explain the several kinds of psychologic discomfort which we have here recognized and studied. We show, at last, some of job's organization modifications rose from the first outcome of our study.
Assuntos
Doenças Profissionais/diagnóstico , Estresse Psicológico/diagnóstico , Humanos , ItáliaRESUMO
OBJECTIVE: Peripheral cholangiocarcinoma may be more frequent than expected, and is usually asymptomatic until it is well advanced. Our purpose was to assess the accuracy of ultrasound in differential diagnosis. METHODS: We compared the sonographic findings of ten consecutive patients with histologically proven peripheral cholangiocarcinoma with those obtained in 26 consecutive patients with hepatocarcinoma detected in the same period. In every patient we performed an ultrasound-guided biopsy with a fine (22 gauge) cutting needle. RESULTS: In all patients with a final diagnosis of peripheral cholangiocarcinoma, the ultrasound scan disclosed multiple well-defined nodules with a hypoechoic or target pattern. Two patients had dilated intrahepatic bile ducts and suspected infiltration of the common duct. No patient had ascites. Only minimal alterations in laboratory examinations were found. Ultrasound-guided fine cutting needle biopsy yielded diagnostic material and allowed the definitive differential diagnosis. CONCLUSION: Peripheral cholangiocarcinoma even in Western countries may represent a significant proportion of all primary liver cancers. Due to non-specific symptomatology only intractable and far advanced cases were detected by means of sonography. Ultrasound findings did not differ from those found in cases of metastases from extrahepatic adenocarcinomas or hepatocarcinoma with multinodular pattern (10/26 in our series).
Assuntos
Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Biópsia por Agulha , Colangiocarcinoma/patologia , Diagnóstico Diferencial , Humanos , UltrassonografiaRESUMO
BACKGROUND: An association between celiac disease and primary biliary cirrhosis has been reported in a few cases, mainly as individual case reports. OBJECTIVES: To screen adult patients with celiac disease for primary biliary cirrhosis and patients with primary biliary cirrhosis for intestinal celiac involvement. METHODS: The celiac group consisted of 336 adults (218 women and 118 men; mean age, 36 yr; range 18-74 yr) with celiac disease diagnosed by serological and histological tests, 38 with newly diagnosed celiac disease and 298 with previously diagnosed celiac disease who were consuming a gluten-free diet. The mean follow-up period was 6 yr (range, 1-16 yr). Liver function parameters and autoantibody levels were determined, and, when indicated, histological tests were performed. The biliary cirrhosis group consisted of 65 subjects (58 women and seven men) (mean age, 59 yr; range, 35-67 yr) with primary biliary cirrhosis diagnosed 1-17 years previously (mean, 7 yr) on the basis of the usual biochemical, serological, and histological criteria. Antigliadin and antiendomysium antibody levels were determined, and two biopsy specimens from the distal duodenum obtained during endoscopy were evaluated. RESULTS: In patients with celiac disease, impairment of liver function was frequently found at diagnosis (16 of 38, or 44%), but primary biliary cirrhosis was diagnosed in only one case. In patients with primary biliary cirrhosis, no cases of celiac disease, as currently defined, were found. CONCLUSIONS: Our findings indicate that celiac disease and primary biliary cirrhosis are rarely associated and support the hypothesis that the intestinal lesions per se are not responsible for the liver disease.
Assuntos
Doença Celíaca/diagnóstico , Cirrose Hepática Biliar/diagnóstico , Adolescente , Adulto , Idoso , Autoanticorpos/sangue , Biópsia , Doença Celíaca/complicações , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Doença Celíaca/fisiopatologia , Dieta com Restrição de Proteínas , Proteínas Alimentares/administração & dosagem , Duodeno/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Seguimentos , Gliadina/análise , Gliadina/imunologia , Glutens/administração & dosagem , Humanos , Imunoglobulina A/sangue , Fígado/fisiopatologia , Cirrose Hepática Biliar/complicações , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/patologia , Cirrose Hepática Biliar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Miofibrilas/química , Miofibrilas/imunologiaRESUMO
BACKGROUND/AIMS: The molecular defect of genetic hemochromatosis (GH) is unknown. It is believed that low expression of duodenal ferritin in GH is caused by tissue or cell specific defect of ferritin synthesis. Our study was designed to ascertain whether the control of duodenal ferritin synthesis in GH was defective. METHODS: Expression at the single cell level of H and L ferritin messenger RNAs and protein and activity of the iron regulatory factor, which controls the translation of ferritin messenger RNA, were assessed in 43 duodenal biopsy specimens from individuals with GH, secondary hemochromatosis (SH), anemia, or normal iron balance. RESULTS: Signal for ferritin H and L subunit messenger RNAs was detected in both absorptive and nonabsorptive cells by in situ hybridization, but in 10 of 14 patients with untreated GH, the signal was lower than in patients with SH or normal subjects. However, immunostaining for ferritin protein documented a diffuse/cytoplasmic pattern, whereas a supranuclear/granular staining was found in normal subjects or patients with SH. The spontaneous activity of duodenal iron regulatory factor was consistently higher in patients with GH than in normal subjects or subjects with anemia or SH. CONCLUSIONS: In patients with GH, ferritin gene transcription is preserved in both absorptive and nonabsorptive intestinal cells. Low accumulation of ferritin is not caused by a defective control of ferritin synthesis but by low expression of ferritin messenger RNA and sustained activity of iron regulatory factor.
Assuntos
Duodeno/metabolismo , Ferritinas/biossíntese , Hemocromatose/genética , Hemocromatose/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Duodeno/patologia , Hemocromatose/patologia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Distribuição TecidualRESUMO
The prevalence of cholelithiasis and possible related factors was evaluated in 350 consecutive patients with alcoholic cirrhosis (218 cases, 174 male and 44 female, mean age 58 +/- 9 years) or genetic haemochromatotic cirrhosis (132 cases, 115 male and 17 female, mean age 53 +/- 10 years). At enrollment patients with alcoholic cirrhosis were significantly older than those with genetic haemochromatotic cirrhosis (P < 0.01), and their clinical status was more severe (Child's class B/C in 99 alcoholic cirrhosis cases versus 27 genetic haemochromatotic cirrhosis cases, P < 0.01). The overall frequency of cholelithiasis was 31% (67 cases) in the alcoholic cirrhosis group and 30% (40 cases) in the genetic haemochromatotic cirrhosis group, without differences according to gender, classes of age (< or = 49, 50-59, > or = 60 years), or HBsAg positivity in either group. In addition, in the genetic haemochromatotic cirrhosis group the presence of diabetes (45 cases), alcohol misuse (38 cases) and beta-thalassemia trait (13 cases) did not influence the prevalence of cholelithiasis. Body mass index, serum cholesterol and triglycerides, and the severity of the underlying liver disease (Child's class) did not distinguish patients with or without cholelithiasis. In conclusion, the frequency of cholelithiasis was high in both alcoholic cirrhosis and genetic haemochromatotic cirrhosis, and was three times higher than that reported in controls from the general population of the same area.
Assuntos
Colelitíase/etiologia , Hemocromatose/genética , Cirrose Hepática Alcoólica/complicações , Cirrose Hepática/genética , Idoso , Índice de Massa Corporal , Colelitíase/diagnóstico , Colelitíase/genética , Colesterol/sangue , Feminino , Hemocromatose/complicações , Hemocromatose/diagnóstico , Humanos , Itália , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática Alcoólica/diagnóstico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangueRESUMO
The relationship of pretreatment serum ferritin and hepatic iron concentration to body iron removed by venesections was evaluated in 33 patients with genetic hemochromatosis. The median values of the three variables considered were 1,950 micrograms/L (range = 255 to 10,000), 1,175 micrograms/100 mg dry weight (range = 270 to 4,310) and 10 gm (range = 2 to 41), respectively. At basal liver biopsy 18 patients had cirrhosis, 6 patients had fibrosis and 9 patients had a normal pattern; siderosis was degree 3 in 6 patients and degree 4 in 27 patients. The results of fitting a polynomial regression of second degree showed that the curve of serum ferritin on iron removed was a straight line (R2 = 0.79, with a significant coefficient of linearity, p less than 0.01, and a nonsignificant coefficient of curvature), whereas that of hepatic iron concentration on iron removed showed a curvature (R2 = 0.62, with significant coefficient of linearity and curvature, p less than 0.01) and reached a plateau. The sigmoid model fit the curve of hepatic iron concentration on iron removed (R2 = 0.61), which suggested a saturation of hepatic iron storage capability; the asymptote corresponded to a hepatic iron concentration of about 2,000 micrograms/100 mg. In alcoholic patients (17 cases) the location of the sigmoid was greater than in nonalcoholic patients. Our results suggest that iron deposition occurs in the liver before other organs are involved and that with massive iron overload hepatic deposits reach saturation, after which hepatic iron concentration does not always reflect the amount of total stores. Alcohol consumption could slow the saturation of hepatic iron deposits.
Assuntos
Hemocromatose/genética , Ferro/metabolismo , Fígado/metabolismo , Adulto , Consumo de Bebidas Alcoólicas , Feminino , Ferritinas/sangue , Hemocromatose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Análise de RegressãoRESUMO
Fifty-six patients with idiopathic hemochromatosis (50 men and 6 women, mean age 49.7 +/- SD 11.1 and 60.8 +/- SD 10.3 years respectively) were studied and followed up for a median period of 44 months (range 3-168). At basal liver biopsy 44 patients had cirrhosis and 12 fibrosis. Iron depletion was achieved in 39 of the 46 cases who underwent iron removal by erythrocytapheresis. Eighteen patients died, 11 from malignancy and 7 from other causes. A total of 14 malignant neoplasms were observed (6 hepatocellular and 8 extrahepatic), of which 6 (5 hepatocellular and 1 pancreatic) were already evident at enrollment. Cumulative survival rates at 3, 5 and 8 years were 75.4%, 64.2% and 54.4% respectively, significantly lower than those in the general population. Probabilities of developing cancer in the 50 patients without cancer at diagnosis were 5.5%, 14.9% and 44.4% at 3, 5 and 8 years respectively.
Assuntos
Hemocromatose/complicações , Hemocromatose/mortalidade , Neoplasias/etiologia , Carcinoma Hepatocelular/etiologia , Feminino , Seguimentos , Hemocromatose/diagnóstico , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Probabilidade , Fatores de TempoRESUMO
In a series of 646 heroin addicts anti-HIV was detected in 428 (66.2%) and HBsAg in 53 (8.2%). Forty-eight (90.5%) of the latter had concomitant chronic HDV infection. Markers of past HBV infection were found in 481 (74.4%). The prevalence of anti-HIV was significantly higher in the 534 subjects with HBV markers than in the other 112 without markers (69.8% versus 49.1%, p less than 0.001). Of the 266 anti-HIV positive subjects followed for 3-48 months (median 12), nine progressed from no disease to persistent generalized lymphadenopathy (PGL), 52 from PGL to AIDS-related complex (ARC) or AIDS (30 and 22 cases respectively), and six from ARC to AIDS. Baseline T4 + cell count was significantly lower and reduction during follow-up significantly greater in heroin addicts with disease progression than in those without.