RESUMO
BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.
Assuntos
Síndrome de Isaacs/complicações , Miastenia Gravis/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Adulto , Autoanticorpos/sangue , Eletromiografia , Feminino , Humanos , Masculino , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Miastenia Gravis/sangue , Recidiva Local de Neoplasia , Netrina-1/imunologia , Estudos Retrospectivos , Timoma/sangue , Neoplasias do Timo/sangueRESUMO
Emerging evidence points to reactive glia as a pivotal factor in Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of basal ganglia injury, but whether astrocytes and microglia activation may exacerbate dopaminergic (DAergic) neuron demise and/or contribute to DAergic repair is presently the subject of much debate. Here, we have correlated the loss and recovery of the nigrostriatal DAergic functionality upon acute MPTP exposure with extensive gene expression analysis at the level of the ventral midbrain (VM) and striata (Str) and found a major upregulation of pro-inflammatory chemokines and wingless-type MMTV integration site1 (Wnt1), a key transcript involved in midbrain DAergic neurodevelopment. Wnt signaling components (including Frizzled-1 [Fzd-1] and ß-catenin) were dynamically regulated during MPTP-induced DAergic degeneration and reactive glial activation. Activated astrocytes of the ventral midbrain were identified as candidate source of Wnt1 by in situ hybridization and real-time PCR in vitro. Blocking Wnt/Fzd signaling with Dickkopf-1 (Dkk1) counteracted astrocyte-induced neuroprotection against MPP(+) toxicity in primary mesencephalic astrocyte-neuron cultures, in vitro. Moreover, astroglial-derived factors, including Wnt1, promoted neurogenesis and DAergic neurogenesis from adult midbrain stem/neuroprogenitor cells, in vitro. Conversely, lack of Wnt1 transcription in response to MPTP in middle-aged mice and failure of DAergic neurons to recover were reversed by pharmacological activation of Wnt/ß-catenin signaling, in vivo, thus suggesting MPTP-reactive astrocytes in situ and Wnt1 as candidate components of neuroprotective/neurorescue pathways in MPTP-induced nigrostriatal DAergic plasticity.
Assuntos
Astrócitos/metabolismo , Astrócitos/patologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Transdução de Sinais/genética , Substância Negra/metabolismo , Substância Negra/patologia , Proteína Wnt1/genética , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/genética , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Vias Neurais/patologia , Transdução de Sinais/efeitos dos fármacos , Substância Negra/efeitos dos fármacosRESUMO
Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.
Assuntos
Doenças Desmielinizantes/diagnóstico por imagem , Doenças Desmielinizantes/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polirradiculoneuropatia/diagnóstico por imagem , Polirradiculoneuropatia/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico por imagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The two chemokines, monocyte chemoattractant protein (MCP)-1 and gamma-interferon inducible protein (IP)-10, are thought to be involved in the pathogenesis of multiple sclerosis (MS). We measured MCP-1 and IP-10 levels in serum and CSF samples from 38 acute and 25 stable MS patients and from 40 controls. The latter consisted in patients with other inflammatory neurological diseases (OIND) or with non-inflammatory neurological diseases, and healthy controls. CSF MCP-1 levels exceeded those found in serum in all the patients studied as well as in healthy controls. CSF MCP-1 levels were significantly lower in acute MS [468+/-(S.E.M.) 18 pg/ml] than in stable MS (857+/-104 pg/ml). When detectable, serum and CSF IP-10 levels were significantly higher in acute MS (serum 331+/-66 pg/ml; CSF 118+/-16 pg/ml) than in stable MS (serum 69+/-7 pg/ml; CSF 25+/-2 pg/ml). Among OIND patients, those with HIV-1-associated dementia showed high serum and CSF levels of both MCP-1 and IP-10. Those with encephalitis showed high serum and CSF levels of IP-10 and CSF mononuclear pleiocytosis. We also evaluated the effects of 6-methylprednisolone or IFN-beta1a therapy on circulating MCP-1 and IP-10 levels. Neither MCP-1 nor IP-10 post-therapy levels varied significantly from baseline values. Our findings suggest that (a) MCP-1 could be constitutively produced within the brain; (b) MCP-1 and IP-10 CSF levels in acute MS vary significantly from those in stable MS, and these variations are inverse; and (c) current MS therapies do not modify circulating levels of MCP-1 and IP-10.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Quimiocina CCL2/metabolismo , Quimiocinas CXC/metabolismo , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Doença Aguda , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Quimiocina CXCL10 , Feminino , Humanos , Interferon beta-1a , Interferon beta/uso terapêutico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Esclerose Múltipla/terapia , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Pro- and anti-inflammatory cytokines are thought to participate in the development and regulation of autoimmunity in multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS). We analysed the percentage of interferon (IFN)-gamma and interleukin (IL)-4-producing cells in the peripheral blood of both active and stable MS patients, and of healthy controls. After short-term stimulation, cytokine-producing cells were intracellularly stained and sorted. Significantly lower percentages of IFN-gamma and IL-4-producing T cells were found in stable MS patients than in controls, and in active than in stable patients. The diminution affected CD4(+) (Th1, Th2) and CD8(+) (Tc1) phenotypes. Tc2 cells were not detected. The Th1/Th2 ratio did not differ in active and stable MS, nor in controls. The fact that Th2 and Tc1 cell percentages were higher in stable than in active MS possibly indicates that these cells play a downmodulating role in the immune response. In contrast, a role in exacerbating the immune response is not attributable to Th1 cells, given their reduction in acute MS. Our data do not support the hypothesis that MS is a Th1/Th2 paradigmatic disease; rather, they suggest that sequestration in the CNS, or activation-induced apoptosis (whether in vivo or in vitro) may explain reduced levels of IFN-gamma and IL-4-producing subsets in the peripheral blood of clinically acute patients.
Assuntos
Interferon gama/biossíntese , Interleucina-4/biossíntese , Esclerose Múltipla/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adolescente , Adulto , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Recidiva , Subpopulações de Linfócitos T/classificaçãoRESUMO
Demyelination is the main pathological feature of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. Tumor necrosis factor-alpha (TNF-alpha) can cause myelin damage and contribute to MS pathogenesis. We measured plasma and cerebrospinal fluid (CSF) levels of TNF-alpha and its soluble receptors, TNF-sRp55 and TNF-sRp75, in 18 patients with active MS, and in neurological and healthy controls. The same determinations were repeated on plasma and on CSF samples that were collected after the MS patients had ended a six-day treatment with high-dose methylprednisolone (MP). Pre- and post-treatment plasma and CSF TNF-alpha levels, when detectable, and those of TNF-sRp75, did not vary, and were similar to those of controls. CSF TNF-sRp55 levels were higher in acute MS patients than in controls. Post-treatment CSF TNF-sRp55 levels were higher than in the active phase of the disease. The MS patients, who clinically improved, tended to have the highest CSF TNF-sRp55 levels. The increase was due to intrathecal TNF-sRp55 synthesis. Although it is involved in MS pathogenesis, TNF-alpha is not detectable in plasma or in CSF samples from MS patients in various phases of the disease. A better marker of disease activity seems to be CSF TNF-sRp55 levels. The increased CSF levels of TNF-sRp55 in response to MP circumstantially suggest that this receptor could partially account for the beneficial effects of MP in acute MS.
Assuntos
Metilprednisolona/uso terapêutico , Esclerose Múltipla/sangue , Esclerose Múltipla/líquido cefalorraquidiano , Receptores do Fator de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Feminino , Humanos , Masculino , Esclerose Múltipla/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/líquido cefalorraquidianoRESUMO
We measured some immunological parameters in 20 hospitalized patients with major depression and 20 age- and sex-matched healthy controls. Both enumeration of immune cells, including T-lymphocyte subpopulations, and assay of T-cell function were studied. White blood cells were evaluated with an automated cell counter, T-cell subsets with an immunobead technique, and T-cell function with a phytohemagglutinin-induced proliferation in vitro assay. We found that T-lymphocyte responses to the mitogen were significantly lower in depressed patients than in controls. All the other parameters were normal. These findings suggest that functional but not numerical changes in T-lymphocytes characterize major depressive disorders.
Assuntos
Transtorno Depressivo/imunologia , Imunidade Celular/imunologia , Ativação Linfocitária/imunologia , Fito-Hemaglutininas/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Antígenos CD8/imunologia , Transtorno Depressivo/diagnóstico , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mitógenos/imunologia , Neuroimunomodulação , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Linfócitos T/imunologiaRESUMO
The results of the analysis of 47 cases of premature rupture of the membranes occurred between 20 and 35 weeks of gestation were reviewed. The aim is to evaluate the natural outcome of this pathology and the advantage of the endocervical application of a human fibrin glue (Tissucol) as a treatment of the cases of premature rupture between 20 and 27 weeks of gestation. This management has been performed at the Obstetric Department of the Università de Verona since 1991 on a total of 5 cases. We demonstrated an evident prolongation of pregnancy leading as a consequence to an increased fetal survival rate. Actually the most important risk factor has to be identified in prematurity.
Assuntos
Ruptura Prematura de Membranas Fetais/terapia , Adesivo Tecidual de Fibrina/uso terapêutico , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da GravidezRESUMO
Post-partum superficial and deep venous thrombosis are still an important obstetric problem. Varicose veins of the lower limbs are closely associated epidemiologically and pathogenically with venous thrombosis. A controlled group of 1,588 parturients was studied to single out other risk factors and to ascertain the prevalence of thrombosis. A group of 1,464 parturients was treated with graduated compression stockings, in low risk patients, adding preventive treatment with low dose heparin in high risk patients. The prevalence of post-partum venous thrombosis was reduced from 4.3%, in the control group, to 0.9% in the study group: in women who received preventive treatment, the prevalence of thrombosis diseases was decreased over 90%.
Assuntos
Heparina/administração & dosagem , Transtornos Puerperais/prevenção & controle , Tromboflebite/prevenção & controle , Bandagens , Cálcio/administração & dosagem , Feminino , Humanos , Gravidez , Tromboflebite/etiologia , Varizes/complicaçõesRESUMO
The Authors report their experience of two pregnancies complicated by polyhydramnios, treated with indomethacin (100 mg/day for 10 and 7 days respectively). The outcome of both pregnancies was foetal intrauterine death. The absence of foetal anomalies incompatible with life and the presence of tissue lesions by asphyxia led the Authors to think that indomethacin might have had a determinant role in the foetal death. This study suggests that the use of indomethacin in polyhydramnios is questionable.
Assuntos
Indometacina/administração & dosagem , Poli-Hidrâmnios/tratamento farmacológico , Adulto , Líquido Amniótico , Diurese/efeitos dos fármacos , Feminino , Humanos , Gravidez , Segundo Trimestre da GravidezRESUMO
The association of extremely diluted concentrations of opioids and local anesthetics appears to be highly promising for pain control during labour. This study examined the efficacy of the association of Fentanyl 100 mcg and Bupivacaine 10 mg in second-stage labour pain and perineal pain. The study which was carried out in 20 patients confirmed the lack of collateral effects on the fetus, mother (except for slight itching in 25% of cases) and the progress of labour. A virtually total elimination of pain was obtained in all cases during the dilatation and expulsion stages. During the second stage of labour pain was completely abolished in 50% of cases, whereas in the remaining 50% it lasted on average for 13 minutes. Perineal analgesia was sufficient to allow episiorrhaphy in 50% of patients without resorting to the use of local anesthetic.
Assuntos
Anestesia Obstétrica/métodos , Bupivacaína/administração & dosagem , Fentanila/administração & dosagem , Trabalho de Parto , Dor/tratamento farmacológico , Anestesia Epidural , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Over the last ten years it has become clear that the clinical expression of celiac disease is more heterogeneous than was thought in the past. Although celiac disease is a relatively frequent disease (1/170-200), it is only diagnosed in a small percentage of adult cases compared to the real situation because it is manifested with few symptoms or in an atypical form, or occasionally is completely silent. Gynecological problems have been reported in women with celiac disease, in particular delayed menarche, early menopause, sterility, recurrent abortion and fetal intrauterine growth retardation. The main aim of this study was to investigate the association between celiac disease and abortion, and in particular to evaluate whether patients suffering from recurrent spontaneous abortion might present an atypical or subclinical form of the disease. METHODS: During the period 1997-1998 a series of laboratory tests were carried out at the Department of Obstetrics and Gynecology and at the Institute of Medicine B of Verona University, in a sample of 184 women (149 from the Obstetrics Clinic and 35 from Internal Medicine B ). These tests included circulating anti-gliadin (AGA) and anti-endomysium (EMA) antibodies and total serum immunoglobulins. In positive cases, further diagnostic tests were performed using small bowel biopsy specimens. RESULTS: In our selected sample of cases, 5 women (2.7%) were positive for immunological screening against IgA-EMA and for bowel biopsy (confirmed diagnosis of celiac disease). Four of these women (2.1%) formed part of a group of patients with a positive history of spontaneous abortion and one (0.5%) was from the control group. CONCLUSIONS: An analysis of the cases that emerged from this study and those reported in the literature shows that tests to identify the celiac disease should be extended to the population with a risk of developing this disease. These subjects should include those with a family history or clinical symptoms, in particular women with a history of multiple abortions. In these cases, there are grounds for suspecting an atypical form of celiac disease.
Assuntos
Aborto Espontâneo/etiologia , Doença Celíaca/complicações , Aborto Habitual/diagnóstico , Aborto Habitual/etiologia , Aborto Espontâneo/diagnóstico , Adulto , Doença Celíaca/diagnóstico , Doença Celíaca/imunologia , Feminino , Fertilidade , Gliadina/imunologia , Humanos , Imunoglobulinas/análise , Infertilidade Feminina , Menarca , Menopausa Precoce , Gravidez , Fatores de RiscoRESUMO
In the first weeks of pregnancy there is a significant increase of vasodilatator prostaglandins in maternal blood. This increase could be in a cause-effect relation with the increase of progesterone, BHCG and HPRL typical of the first phase of pregnancy. Blood samples of 12 normotensive women reveal that there is not a correlation between placental hormons, HPRL and the increase of prostaglandins, but these hormones seem to offer an important control on other more complex biochemical mechanisms that cause the increase of vasodilator prostaglandins.
Assuntos
Hormônios Placentários/sangue , Progesterona/sangue , Prolactina/sangue , Prostaglandinas/urina , Pressão Sanguínea/fisiologia , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Prostaglandinas/sangue , Prostaglandinas/química , VasodilatadoresRESUMO
The Authors report their diagnostic experience of 263 patients with abnormal uterine bleeding in peri- and post-menopause. They used a diagnostic procedure which favored the hysteroscopy in first level research: hysteroscopy proved to be a reliable and easily applicable method. In fact it has demonstrated the high incidence of functional pathology (135 cases) and has permitted the histological control of the 3 high risk hyperplasia and of the 15 adenocarcinomatas found in their patients.
Assuntos
Hiperplasia Endometrial/complicações , Menopausa , Metrorragia/etiologia , Neoplasias Uterinas/complicações , Adulto , Hiperplasia Endometrial/diagnóstico , Feminino , Humanos , Histeroscopia , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Uterinas/diagnósticoRESUMO
BACKGROUND: The objective of this study is to determine whether or not the measurement of hCG levels in the washing fluid of the posterior vaginal fornix is useful for the diagnosis of premature rupture of membranes. METHODS: Samples were analysed from 52 normal pregnant women, divided into three groups: 20 pregnant women without rupture of membranes, 21 patients with confirmed rupture of membranes, 11 patients with suspected rupture of membranes. In order to distinguish patients of the two groups we propose a hCG cut-off value of 100 mIU/ml. RESULTS: The analysis of our data reveals that there is no overlapping between the hCG levels of the group of pregnant women without rupture of membranes and the group of patients with confirmed rupture of membranes. CONCLUSIONS: The hCG levels in the washing fluid of the posterior vaginal fornix in our experience is a useful, very cheap and non-invasive diagnostic test of PROM.
Assuntos
Gonadotropina Coriônica/análise , Ruptura Prematura de Membranas Fetais/diagnóstico , Vagina , Feminino , Humanos , Gravidez , Irrigação TerapêuticaRESUMO
The offspring of the diabetic mother is more significantly affected by RDS (Respiratory Distress Syndrome) than the healthy pregnancy's one in the same conditions. The RDS is one of the most important cause of perinatal morbidity and mortality. The etiology of this syndrome is recognized in the modified carbohydrates metabolism, in the apposite effect of insulin versus the cortisol action, and in the slower adsorption of the alveolar fluid following the Cesarean section. In fact the diabetic mother is frequently submitted to this intervention to end the pregnancy and especially in last years when the CS was of first choice at 35 weeks in the diabetic mothers. Actually the RDS appears in the 13% of the offspring of mothers affected by pregestational diabetes and in the 5% of the offspring of gestational diabetic mothers. Here we refer about the prevalence of RDS in a population of 55 diabetic mothers.
Assuntos
Diabetes Gestacional , Gravidez em Diabéticas , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Adulto , Peso ao Nascer , Cesárea , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , PrevalênciaRESUMO
Congenital malformations are considered the more frequent perinatal complications affecting offsprings of diabetic mothers; they represent the main cause of mortality of these neonates. Since diabetes is strictly controlled, the incidence and the seriousness of its complications are reduced from 8-10% to 2-3%. In this study we followed 56 pregnancies complicated by diabetes. There were 3 case of malformations. We correlate these with the metabolic maternal balance and with the HbA1c values. We could confirm the relationship between malformation and metabolic imbalance and also the absence of fetal malformations in women with metabolic compensation since the beginning of the pregnancy.
Assuntos
Anormalidades Congênitas/etiologia , Diabetes Gestacional/metabolismo , Gravidez em Diabéticas/metabolismo , Adulto , Anormalidades Congênitas/prevenção & controle , Diabetes Gestacional/prevenção & controle , Feminino , Humanos , Recém-Nascido , Idade Materna , Pessoa de Meia-Idade , Gravidez , Fatores de RiscoRESUMO
Our experience of beta-thalassemia during pregnancy is limited to 2 rare cases. The first patient suffered from beta(0)/beta(+) thalassemia, and therapy consisted of 300 ml of concentrated red cells every month and deferoxamine. During pregnancy the patient received 300 ml of concentrated red cells every week, and a healthy child was born by cesarean section. The second patient suffered from Cooley's disease till 1985. She received many transfusions but was allergic to deferoxamine. Later, bone marrow transplantation was successful. Her normal full-term pregnancy concluded with the birth of a healthy child.