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1.
Autoimmun Rev ; 21(4): 103038, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34995765

RESUMO

BACKGROUND: Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function. OBJECTIVE: This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE. METHODS: This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Studies selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool. RESULTS: Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.28, 95%-CI [0.14; 0.55]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF. CONCLUSION: The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.


Assuntos
Lúpus Eritematoso Sistêmico , Insuficiência Ovariana Primária , Adulto , Estudos Transversais , Ciclofosfamida/uso terapêutico , Feminino , Fertilidade , Humanos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/complicações , Insuficiência Ovariana Primária/tratamento farmacológico
2.
Eur Rev Med Pharmacol Sci ; 24(12): 6893-6898, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32633382

RESUMO

OBJECTIVE: Primary headache disorders in children are one of the most prominent topics in the pediatric neurology literature. However, there are many unsolved aspects, including the conditions associated with migraine. The present study aims to report on the frequency of behavioral comorbidities in the setting of primary headache in childhood. PATIENTS AND METHODS: In this study, we enlisted 475 children (290 males and 185 females; ratio 1.6:1), aged 4 to 14 years, who were affected by primary headache. In direct interviews, children and parents gave information on the association of their headache with, attention-deficit/hyperactivity disorder, learning disabilities, tics, anxiety, depression, and obsessive-compulsive disorder. Other 475 children with no history of headache or recognized neurological conditions were matched for age, sex, race, and socioeconomic status and were used as controls. RESULTS: A significant association of primary headache was found with anxiety and depression (p-value <0.001); overall, behavioral disorders were more common in children who experienced headache than in controls (p-value <0.001). CONCLUSIONS: Primary headache in children is not associated with most of the common behavioral conditions. On the contrary, there was a significant association with anxiety and depression, as reported in adults.


Assuntos
Transtornos de Ansiedade/complicações , Depressão/complicações , Cefaleia/complicações , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Itália , Masculino , Classe Social
3.
Biol Blood Marrow Transplant ; 26(5): 893-901, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31982543

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib before HCT (n = 32), and those with splenomegaly >22 cm received pretransplantation splenic irradiation. The median age at HCT was 60 years (range, 40 to 74 years), and 68% of the cohort carried a JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning; 22 patients (59%) received a reduced-intensity conditioning regimen. All patients received peripheral blood grafts, from a matched sibling donor in 16 patients (43%), an unrelated donor in 20 patients, and a haploidentical-related donor in 1 patient. Sixty-one percent had a Hematopoietic Cell Transplantation Comorbidity Index ≥3, 40% had a Karnofsky Performance Status score <90, and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9 to 115 months), the 3-year overall survival and relapse-free survival were 81.1% (95% confidence interval [CI], 64.4% to 90.5%) and 78.4% (95% CI, 61.4% to 88.5%), respectively. Only 2 patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5% to 29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplantation for graft-versus-host disease, graft rejection/relapse, or persistent MF. These results suggest that pretransplantation ruxolitinib, fludarabine/busulfan-based conditioning, and splenic management are keys to improved transplantation outcomes in patients undergoing allo-HCT for MF.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Idoso , Bussulfano , Humanos , Nitrilas , Mielofibrose Primária/terapia , Pirazóis , Pirimidinas , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados
4.
Lupus ; 28(9): 1091-1100, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31291846

RESUMO

BACKGROUND: The study aimed to investigate whether HLA-G antigen is expressed in the kidneys of patients affected by lupus nephritis (LN) and whether its detection in renal biopsies could be adopted as a marker of treatment response and prognosis. METHODS: Thirty renal biopsies from patients with LN were selected and analyzed through immunohistochemistry. Laboratory and clinical data were retrospectively collected at baseline, 6 and 12 months and at the latest clinical appointment. A number of patients (63.3%) were treated with rituximab (RTX) +/- methylprednisolone in the induction phase. The expression of HLA-G in glomeruli, tubules and infiltrating cells was examined and compared between lupus patients who achieved either complete or partial renal response and those who did not respond to treatment. RESULTS: HLA-G staining was observed in the glomeruli of 20 of 30 samples from patients with LN. The expression of the antigen was detected in podocytes, along glomerular capillary walls, on parietal glomerular epithelial cells and within the juxtaglomerular apparatus. Seventy per cent of patients whose glomeruli expressed HLA-G achieved partial or complete response at 6 months and 75% at the latest available follow up compared with 30% and 40%, respectively, of those who did not show any expression. The pattern of staining in tubules and infiltrating cells was highly variable precluding any clinical correlation. CONCLUSION: This study demonstrates that HLA-G is expressed in renal tissue in LN. Our retrospective data suggest that its expression could correlate with response to treatment.


Assuntos
Antígenos HLA-G/imunologia , Nefrite Lúpica/tratamento farmacológico , Metilprednisolona/administração & dosagem , Rituximab/administração & dosagem , Adulto , Anti-Inflamatórios/administração & dosagem , Biópsia , Feminino , Seguimentos , Humanos , Fatores Imunológicos/administração & dosagem , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
5.
Eur J Neurol ; 26(9): 1226-1234, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31132195

RESUMO

BACKGROUND AND PURPOSE: Congenital disorders of glycosylation (CDG) represent an increasing number of rare inherited metabolic diseases associated with abnormal glycan metabolism and disease onset in infancy or early childhood. Most CDG are multisystemic diseases mainly affecting the central nervous system. The aim of the current study was to investigate hyperkinetic movement disorders in patients affected by CDG and to characterize phenomenology based on CDG subtypes. METHODS: Subjects were identified from a cohort of patients with CDG who were referred to the University Hospital of Catania, Italy. Patients were evaluated by neurologists with expertise in movement disorders and videotaped using a standardized protocol. RESULTS: A variety of hyperkinetic movement disorders was detected in eight unrelated CDG patients. Involuntary movements were generally observed early in childhood, maintaining a clinical stability over time. Distribution ranged from a generalized, especially in younger subjects, to a segmental/multifocal involvement. In patients with phosphomannomutase 2 CDG, the principal movement disorders included dystonia and choreo-athetosis. In patients affected by other CDG types, the movement disorders ranged from pure generalized chorea to mixed movement disorders including dystonia and complex stereotypies. CONCLUSIONS: Hyperkinetic movement disorder is a key clinical feature in patients with CDG. CDG should be considered in the differential diagnosis of childhood-onset dyskinesia, especially when associated with ataxia, developmental delay, intellectual disability, autism or seizure disorder.


Assuntos
Defeitos Congênitos da Glicosilação/complicações , Hipercinese/etiologia , Transtornos dos Movimentos/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Itália , Masculino
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2019: 60-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31945845

RESUMO

Development and in-vivo validation of a Continuous Wave (CW) functional Near Infrared Spectroscopy (fNIRS) system is presented. The system is wearable, fiber-less, multi-channel (16×16, 256 channels) and expandable and it relies on silicon photomultipliers (SiPMs) for light detection. SiPMs are inexpensive, low voltage and resilient semiconductor light detectors, whose performances are analogous to photomultiplier tubes (PMTs). The advantage of SiPMs with respect to PMTs is that they allow direct contact with the scalp and avoidance of optical fibers. In fact, the coupling of SiPMs and light emitting diodes (LEDs) allows the transfer of the analog signals to and from the scalp through thin electric cables that greatly increase the system flexibility. Moreover, the optical probes, mechanically resembling electroencephalographic electrodes, are robust against motion artifacts. In order to increase the signal-to-noise-ratio (SNR) of the fNIRS acquisition and to decrease ambient noise contamination, a digital lock-in technique was implemented through LEDs modulation and SiPMs signal processing chain. In-vivo validation proved the system capabilities of detecting functional brain activity in the sensorimotor cortices. When compared to other state-of-the-art wearable fNIRS systems, the single photon sensitivity and dynamic range of SiPMs can exploit the long and variable interoptode distances needed for estimation of brain functional hemodynamics using CW-fNIRS.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Dispositivos Eletrônicos Vestíveis , Encéfalo , Eletroencefalografia , Processamento de Sinais Assistido por Computador
7.
Rev. otorrinolaringol. cir. cabeza cuello ; 78(2): 207-212, jun. 2018. ilus
Artigo em Espanhol | LILACS | ID: biblio-961617

RESUMO

RESUMEN Las metástasis de la columna vertebral cervical no se ven comúnmente en el área otorrinolaringológica, y por lo tanto corren el riesgo de pasar por alto durante la evaluación del paciente. Presentamos un caso inusual evaluado debido a las metástasis de la columna cervical de un tumor primario desconocido. Después de extensos procedimientos de estudio que no eran diagnósticos, se obtuvo una biopsia mediante un abordaje cervical extendido. El paciente fue diagnosticado con un linfoma anaplásico, una enfermedad muy rara en la región de cabeza y cuello. Discutimos los hallazgos histológicos y la presentación clínica de esta condición.


ABSTRACT Cervical spine metastases are not commonly seen in the otolaryngology clinic and therefore run the risk of being overlooked during patient evaluation. We report an unusual case evaluated due to cervical spine metastases from an unknown primary tumor. After extensive workup procedures that were non-diagnostic, a biopsy was obtained through an extended cervical approach. The patient was diagnosed with an anaplastic lymphoma, a very rare disease in the head and neck region. We discuss the histologic findings and clinical presentation of this condition.


Assuntos
Humanos , Masculino , Idoso , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Doença de Hodgkin , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Metástase Neoplásica
8.
Mediators Inflamm ; 2018: 7019398, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29769837

RESUMO

Adenosine (ADO) is an immunosuppressive molecule, which suppresses the immune responses by interacting with specific receptors expressed by immune effector cells. ADO is produced from ATP through the enzymatic activities of CD39 and CD73. Alternatively, ADO can be generated starting from NAD+, which is metabolized by the concerted action of CD38, CD203a/PC-1, and CD73. The role of ADO in immunity has been characterized in the last years in physiology and in pathological settings. This review examines a panel of reports focused on the functions of ADO in the context of human autoimmune/inflammatory diseases and the selected animal models. The final aim is to consider the role of adenosinergic ectoenzymes and ADO receptors as novel therapeutic targets for selected diseases.


Assuntos
Adenosina/metabolismo , Doenças Autoimunes/metabolismo , 5'-Nucleotidase/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Animais , Antígenos CD/metabolismo , Apirase/metabolismo , Humanos
9.
J Viral Hepat ; 24(11): 1016-1022, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28429836

RESUMO

Hepatitis B virus (HBV) infection is a global health problem. The mechanisms of immune tolerance in HBV infection are still unclear. The host immune response plays a critical role in determining the outcome of HBV infection. Human leucocyte antigen-G (HLA-G) is involved in immunotolerogenic process and infectious diseases. This study aimed to explore the implication of soluble HLA-G (sHLA-G) and its isoforms in HBV infection. Total sHLA-G (including shedding HLA-G1 and HLA-G5) was analysed by ELISA in 95 chronic HBV patients, 83 spontaneously resolvers and 100 healthy controls (HC). To explore the presence of sHLA-G dimers, we performed an immunoprecipitation and a Western blot analysis on positive samples for sHLA-G in ELISA. The serum levels of sHLA-G were significantly increased in patients with chronic HBV patients compared to spontaneously resolvers and HC (P<.0001). Interestingly, we found an increased level of sHLA-G1 in chronic HBV patients than in spontaneously resolvers and HC (P<.001). In addition, the expression of HLA-G5 seems to be higher in the sera of chronic HBV patients than spontaneously resolvers (P=.026). The analysis of HLA-G dimers showed the presence of homodimers in 93% of chronic HBV patients, 67% in spontaneously resolvers and 60% in HC. These results provide evidence that sHLA-G may have a crucial role in the outcome of HBV infection and could be proposed as a biomarker for infection outcome. Based on its tolerogenic function, HLA-G might be considered as a new promising immunotherapeutic approach to treat the chronic infection with HBV.


Assuntos
Antígenos HLA-G/sangue , Antígenos HLA-G/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/epidemiologia , Adulto , Biomarcadores , Western Blotting , Feminino , Antígenos HLA-G/química , Vírus da Hepatite B/imunologia , Hepatite B Crônica/virologia , Humanos , Testes de Função Hepática , Masculino , Vigilância da População , Multimerização Proteica , Tunísia/epidemiologia , Adulto Jovem
10.
Int J Oral Maxillofac Surg ; 45(11): 1438-1444, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27609710

RESUMO

Mandibular distraction osteogenesis (MDO) has been widely adopted in modern maxillofacial surgery due to its less invasive approach and the consistent aesthetic and functional improvements obtained. The aim of the present systematic review was to analyze the available evidence on the skeletal and soft tissue effects of MDO. The medical literature was searched to identify all peer-reviewed papers meeting the selection criteria for the final review process. A three-point grading system was used to rate the methodological quality of the selected papers. The PICO approach was used to extract data from the selected papers. The search strategy yielded eight relevant publications. The quality of the collected evidence was low to moderate. Vertical and sagittal skeletal dimensions increased significantly, by a mean of 5-10mm (P<0.05). Regarding the sagittal positioning of the lips and surrounding structures, a 90% correspondence between skeletal and soft tissue cephalometric points was observed. Significant skeletal relapse was reported, however it did not worsen the results of treatment significantly.


Assuntos
Mandíbula/cirurgia , Osteogênese por Distração/métodos , Cefalometria , Tecido Conjuntivo/anatomia & histologia , Estética Dentária , Humanos , Mandíbula/anatomia & histologia , Complicações Pós-Operatórias , Crânio/anatomia & histologia
12.
HLA ; 87(3): 153-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26956431

RESUMO

Chronic hepatitis B virus (HBV) infection occurs in association to a deregulation of immune system. Human leukocyte antigen E (HLA-E) is an immune-tolerant nonclassical HLA class I molecule that could be involved in HBV progression. To measure soluble (s) HLA-E in patients with chronic HBV hepatitis (CHB). We tested the potential association of HLA-E*01:01/01:03 A > G gene polymorphism to CHB. Our cohort consisted of 93 Tunisian CHB patients (stratified in CHB with high HBV DNA levels and CHB with low HBV DNA levels) and 245 healthy donors. Plasma sHLA-E was determined using enzyme-linked immunosorbent assay (ELISA). Genotyping was performed using polymerase chain reaction sequence-specific primer. No association between HLA-E*01:01/01:03 A > G polymorphism and HBV DNA levels in CHB patients was found. G/G genotype is less frequent in CHB patients without significance. sHLA-E is significantly enhanced in CHB patients compared with healthy controls (P = 0.0017). Stratification according to HBV DNA levels showed that CHB patients with low HBV DNA levels have higher sHLA-E levels compared with CHB patients with high HBV DNA levels. CHB patients with G/G genotype have enhanced sHLA-E levels compared with other genotypes (P = 0.037). This significant difference is maintained only for CHB women concerning G/G genotypes (P = 0.042). Finally, we reported enhanced sHLA-E in CHB patients with advanced stages of fibrosis (P = 0.032). We demonstrate, for the first time, the association of sHLA-E to CHB. Owing to the positive correlation of HLA-E*01:01/01:03 A > G polymorphism and the association of sHLA-E to advanced fibrosis stages, HLA-E could be a powerful predictor for CHB progression. Further investigations will be required to substantiate HLA-E role as a putative clinical biomarker of CHB.


Assuntos
DNA Viral/sangue , Hepatite B Crônica/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Cirrose Hepática/imunologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Genótipo , Vírus da Hepatite B/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Antígenos de Histocompatibilidade Classe I/sangue , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Antígenos HLA-E
13.
Eur J Neurol ; 23(2): 241-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26498733

RESUMO

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.


Assuntos
Anticonvulsivantes/farmacologia , Síndrome de Lennox-Gastaut , Lobo Occipital/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Adolescente , Adulto , Áustria , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Síndrome de Lennox-Gastaut/fisiopatologia , Masculino , Prognóstico , Estudos Retrospectivos , Adulto Jovem
14.
Int J Immunopathol Pharmacol ; 28(3): 434-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25875601

RESUMO

Sinonasal polyposis (SNP) is a chronic inflammatory disease of nasal and paranasal cavities. Human leukocyte antigen-G molecules (HLA-G) are non-classic HLA-I molecules with anti-inflammatory and tolerogenic properties. HLA-G production is mainly induced by interleukin (IL)-10. IL-10 is an anti-inflammatory cytokine that inhibits the production of proinflammatory cytokines and induces HLA-class II down-modulation. Recent studies suggest that HLA-G could play a role in SNP pathogenesis; in SNP patients physiological levels of IL-10 (produced by activated peripheral blood CD14+ monocytes) are not able to induce production of HLA-G. Different mechanisms could justify these findings: genomic or amino-acidic sequence alterations in IL-10 lower IL-10 receptor expression, lower IL-10 receptor affinity, or alterations of the intracellular signal transmission. This study analyzes nucleotidic sequence of IL-10 gene in SNP patients. Sequencing of IL-10 gene shows that the lack of HLA-G production by peripheral blood CD14+ monocytes is not related to alterations in IL-10 gene nucleotidic sequence.


Assuntos
Interleucina-10/genética , Pólipos Nasais/genética , Adulto , Citocinas/genética , Feminino , Antígenos HLA-G/genética , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Receptores de Lipopolissacarídeos/genética , Masculino , Monócitos/metabolismo , Receptores de Interleucina-10/genética
15.
J Viral Hepat ; 22(10): 835-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25619305

RESUMO

Identification of an HLA-G 14-bp Insertion/Deletion (Ins/Del) polymorphism at the 3' untranslated region of HLA-G revealed its importance in HLA-G mRNA stability and HLA-G protein level variation. We evaluated the association between the HLA-G 14-bp Ins/Del polymorphism in patients with chronic Hepatitis B virus (HBV) infection in a case-control study. Genomic DNA was extracted from 263 patients with chronic HBV hepatitis and 246 control subjects and was examined for the HLA-G 14-bp Ins/Del polymorphism by PCR. The polymorphic variants were genotyped in chronic HBV seropositive cases stratified according to HBV DNA levels, fibrosis stages and in a control population. There was no statistical significant association between the 14-bp Ins/Del polymorphism and increased susceptibility to HBV infection neither for alleles (P = 0.09) nor for genotypes (P = 0.18). The stratification of HBV patients based on HBV DNA levels revealed an association between the 14-bp Ins/Del polymorphism and an enhanced HBV activity with high HBV DNA levels. In particular, the Ins allele was significantly associated with high HBV DNA levels (P = 0.0024, OR = 1.71, 95% CI 1.2-2.4). The genotype Ins/Ins was associated with a 2.5-fold (95% CI, 1.29-4.88) increased risk of susceptibility to high HBV replication compared with the Del/Del and Ins/Del genotypes. This susceptibility is linked to the presence of two Ins alleles. No association was observed between the 14-bp Ins/Del polymorphism and fibrosis stage of HBV infection. We observed an association between the 14-bp Ins/Del polymorphism and high HBV replication characterized by high HBV DNA levels in chronic HBV patients. These results suggest a potential prognostic value for disease outcome evaluation.


Assuntos
Antígenos HLA-G/genética , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Mutação INDEL , Polimorfismo Genético , Replicação Viral , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
16.
Eur J Pediatr ; 174(3): 279-88, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25224657

RESUMO

UNLABELLED: Attention deficit hyperactivity disorder (ADHD) is the most common comorbid condition in patients with Tourette syndrome (TS). The co-occurrence of ADHD and TS is in most cases associated with a higher social and psychopathological impairment. Comorbidity between Tourette and ADHD appears to have a complex and partially known pathogenesis in which genetic, environmental, and neurobiological factors can be implicated. Genetic studies have revealed an involvement of dopaminergic, catecholaminergic, and GABAergic genes that modulated the activity of neurotransmitters. Furthermore, there are a lot of networks implicated in the development of ADHD and TS, involving cortical and striatal areas and basal ganglia. Although a large number of studies tried to find a common pathogenesis, the complex pathways responsible are not clear. The genes implicated in both disorders are currently unidentified, but it is probable that epigenetic factors associated with neural modifications can represent a substrate for the development of the diseases. CONCLUSION: In this paper, recent advances in neurobiology of ADHD and TS are reviewed, providing a basis for understanding the complex common pathogenesis underlying the frequent co-occurrence of the two conditions and the therapeutic choices.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Síndrome de Tourette/etiologia , Síndrome de Tourette/patologia , Síndrome de Tourette/terapia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Comorbidade , Meio Ambiente , Epigênese Genética , Humanos , Vias Neurais/patologia , Neurotransmissores/genética , Fatores de Risco , Síndrome de Tourette/epidemiologia , Síndrome de Tourette/genética , Síndrome de Tourette/fisiopatologia
17.
Am J Transplant ; 15(2): 461-71, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25488753

RESUMO

Human leukocyte antigen G (HLA-G) expression is thought to be associated with a tolerance state following solid organ transplantation. In a lung transplant (LTx) recipient cohort, we assessed (1) the role of HLA-G expression as a predictor of graft acceptance, and (2) the relationship between (i) graft and peripheral HLA-G expression, (ii) HLA-G expression and humoral immunity and (iii) HLA-G expression and lung microenvironment. We prospectively enrolled 63 LTx recipients (median follow-up 3.26 years [min: 0.44-max: 5.03]). At 3 and 12 months post-LTx, we analyzed graft HLA-G expression by immunohistochemistry, plasma soluble HLA-G (sHLA-G) level by enzyme-linked immunosorbent assay, bronchoalveolar lavage fluid (BALF) levels of cytokines involved in chronic lung allograft dysfunction (CLAD) and anti-HLA antibodies (Abs) in serum. In a time-dependent Cox model, lung HLA-G expression had a protective effect on CLAD occurrence (hazard ratio: 0.13 [0.03-0.58]; p = 0.008). The same results were found when computing 3-month and 1-year conditional freedom from CLAD (p = 0.03 and 0.04, respectively [log-rank test]). Presence of anti-HLA Abs was inversely associated with graft HLA-G expression (p = 0.02). Increased BALF level of transforming growth factor-ß was associated with high plasma sHLA-G level (p = 0.02). In conclusion, early graft HLA-G expression in LTx recipients with a stable condition was associated with graft acceptance in the long term.


Assuntos
Rejeição de Enxerto/sangue , Rejeição de Enxerto/epidemiologia , Antígenos HLA-G/sangue , Transplante de Pulmão , Transplantados , Adulto , Biomarcadores/sangue , Líquido da Lavagem Broncoalveolar/química , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Fator de Crescimento Transformador beta/análise
18.
Int J Immunopathol Pharmacol ; 27(3): 371-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25280028

RESUMO

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) is a well-defined syndrome in which tics (motor and/or vocal) and/or obsessive compulsive disorders (OCD) consistently exacerbate in temporal correlation to a Group A beta-haemolytic streptococcal infection. In children with PANDAS, there is speculation about whether tonsillectomy or adenotonsillectomy might improve the neuropsychiatric course. Our objective was to examine whether such surgery impacted remission or, in patients without remission, modified clinical course of the disease, streptococcal antibody titers, neuronal antibodies or clinical severity of Obsessive-Compulsive Disorder (OCD) and/or tics. Study participants (n = 120) with positive PANDAS criteria were recruited, examined, and divided into surgical or non-surgery groups. The surgical group consisted of children with tonsillectomy or adenotonsillectomy (n=56). The remaining children were categorized as non-surgery (n=64). Clinical follow-up was made every 2 months for more than 2 years. Surgery did not affect symptomatology progression, streptococcal and neuronal antibodies, or the clinical severity of neuropsychiatric symptoms in these children. In conclusion, in our series clinical progression, antibody production, and neuropsychiatric symptom severity did not differ on the basis of surgical status. We cannot uphold surgical management as likely to impact positive remission rates, course of OCD/tics, or antibody concentrations in children with PANDAS.


Assuntos
Doenças Autoimunes/etiologia , Transtorno Obsessivo-Compulsivo/etiologia , Infecções Estreptocócicas/complicações , Streptococcus pyogenes , Tiques/etiologia , Tonsilectomia , Adenoidectomia , Criança , Feminino , Humanos , Masculino
19.
Tissue Antigens ; 83(2): 113-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24397524

RESUMO

Human papillomavirus (HPV) infection is involved in cervical lesion development. It interferes with host immune response and modifies the expression of human leukocyte antigen-G (HLA-G), a nonclassical HLA-I antigen with immune-inhibitory functions. We analyzed the frequencies of two HLA-G 3' untranslated region polymorphisms (14 bp ins/del, +3142C>G), involved in HLA-G modulation, in 33 condyloma acuminatum, 14 low grade squamous intraepithelial lesion and 100 invasive cervical cancer (ICC) HPV infected patients. We showed the involvement of HLA-G polymorphisms in HPV infection and lesion development, and suggested that 14 bp del allele promotes high-risk HPV infection, with del/C haplotype associated with ICC development. On the basis of these evidences, HLA-G polymorphisms could represent a risk factor in HPV positive subjects.


Assuntos
Regiões 3' não Traduzidas , Condiloma Acuminado/genética , Antígenos HLA-G/genética , Neoplasias de Células Escamosas/genética , Infecções por Papillomavirus/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Alelos , Condiloma Acuminado/imunologia , Condiloma Acuminado/patologia , Condiloma Acuminado/virologia , Feminino , Predisposição Genética para Doença , Antígenos HLA-G/imunologia , Haplótipos , Humanos , Neoplasias de Células Escamosas/imunologia , Neoplasias de Células Escamosas/patologia , Neoplasias de Células Escamosas/virologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Polimorfismo Genético , Fatores de Risco , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
20.
Perfusion ; 29(3): 272-4, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24104209

RESUMO

Coagulopathy can sometimes be observed when CPB times are prolonged. Correction of coagulopathy post CPB can present the surgical team with a number of challenges, including right ventricular volume overload, hemodilution, anemia and excessive cell salvage with further loss of coagulation factors. Restoration of the coagulation cascade on CPB may help to avoid these issues. This case report is of a 64-year-old male with a delayed diagnosis of aortic dissection. The patient presented to the cardiac surgery operating room with hepatic and renal shock/failure, with the resulting coagulopathy. The described technique is representative of a technique that we sometimes employ to restore the clotting mechanism before separating from bypass.


Assuntos
Coagulação Sanguínea , Transfusão de Componentes Sanguíneos , Coagulação Intravascular Disseminada/terapia , Plasma , Fatores de Coagulação Sanguínea , Ponte Cardiopulmonar , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/metabolismo , Humanos , Pessoa de Meia-Idade
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