RESUMO
AIMS/HYPOTHESIS: We aimed to study diurnal variation in glucose regulation by examining the effects of time of day and fasting duration on fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA(1c) levels. METHODS: We analysed data from 5,978 non-diabetic white men and women from the prospective Whitehall II Study. All studied participants fasted for at least 8 h before a clinical examination, which included an OGTT and anthropometric measurements. We fitted mixed-effects models for FPG, 2hPG and HbA(1c) as outcome variables, and time of day and/or fasting duration as explanatory variables. Models were adjusted for age, BMI and study phase. RESULTS: Time of day and fasting duration were associated inversely with FPG and positively with 2hPG. The mean difference between measures at 08:00 and 15:00 hours in men/women was -0.46 (95% CI -0.50, -0.42) mmol/l/-0.39 (95% CI -0.46, -0.31) mmol/l and 1.39 (95% CI 1.25, 1.52) mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA(1c) levels were independent of either time. Time of day and fasting duration were independently associated with 2hPG. In contrast, the effect of fasting duration on FPG was markedly attenuated with adjustment for time of day. Ageing, but not obesity, was associated with increased diurnal variation in glucose tolerance. CONCLUSIONS/INTERPRETATION: Both time of day and fasting duration should be considered in clinical practice and epidemiological studies, since they have clinically relevant effects on FPG and 2hPG levels. As biochemically expected, HbA(1c) levels are independent of time of blood sampling and fasting duration.
Assuntos
Glicemia/metabolismo , Jejum/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVES: The aim of our study was to evaluate placental three-dimensional power Doppler indices in diabetic pregnancies in the second and third trimesters and to compare them with those of the normal controls. METHODS: Placental vascularization of pregnant women was determined by three-dimensional power Doppler ultrasound technique. The calculated indices included vascularization index (VI), flow index (FI), and vascularization flow index (VFI). Uncomplicated pregnancies (n = 113) were compared with pregnancies complicated by gestational diabetes mellitus (n = 56) and diabetes mellitus (n = 43). RESULTS: The three-dimensional power Doppler indices were not significantly different between the two diabetic subgroups. All the indices in diabetic patients were significantly reduced compared with those in non-diabetic individuals (p < 0.001). Placental three-dimensional power Doppler indices are slightly diminished throughout diabetic pregnancy [regression coefficients: -0.23 (FI), -0.06 (VI), and -0.04 (VFI)] and normal pregnancy [regression coefficients: -0.13 (FI), -0.20 (VI), and -0.11 (VFI)]. The uteroplacental circulation (umbilical and uterine artery) was not correlated significantly to the three-dimensional power Doppler indices. If all placental indices are low during late pregnancy, then the odds of the diabetes are significantly high (adjusted odds ratio: 1.10). CONCLUSIONS: A decreased placental vascularization could be an adjunct sonographic marker in the diagnosis of diabetic pregnancy in mid-gestation and late gestation.
Assuntos
Diabetes Gestacional/diagnóstico por imagem , Placenta/irrigação sanguínea , Placenta/diagnóstico por imagem , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal/métodos , Adulto , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Feminino , Indicadores Básicos de Saúde , Humanos , Imageamento Tridimensional , Circulação Placentária/fisiologia , Gravidez , Ultrassonografia Doppler , Artérias Umbilicais/diagnóstico por imagem , Artéria Uterina/diagnóstico por imagemRESUMO
Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.
Assuntos
Esôfago de Barrett/patologia , Esôfago/patologia , Mucosa/patologia , Lesões Pré-Cancerosas/patologia , Adulto , Idoso , Biópsia , Esofagoscopia , Feminino , Células Caliciformes/patologia , Humanos , Masculino , Metaplasia , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: - At present, surgical strategies for breast cancer patients with >2 lymph nodes (LN) involved differ from those with no or lower degree of nodal involvement. Preoperative assessment of the axilla is less sensitive in patients with lobular carcinoma (ILC) than patients with other histological tumour types. MATERIALS AND METHODS: - A retrospective analysis of axillary staging by palpation, axillary ultrasound (AXUS) and AXUS-guided fine-needle aspiration cytology (FNAC) of 153 patients with ILC diagnosed and operated on between January 2013 and December 2020 was performed. Patients had either sentinel node biopsy or axillary lymph node dissection according to current practice. In period 1, patients had FNAC only when AXUS suggested nodal involvement (n = 106), and in period 2, all ILC patients had axillary FNAC (n = 47). RESULTS: - Of the factors associated with >2LNs involvement, logistic regression suggested only AXUS/FNAC based staging as independent variable for all patients. Patients with AXUS-guided FNAC had a significantly higher proportion of true negative and lower proportion of true positive cases in the P2 period (0 vs 55% and 72% vs 11% for >2 LNs involvement, respectively; both p < 0.0001). CONCLUSIONS: - AXUS-guided FNAC of all ILC patients did not result in improved preoperative identification of patients with >2 metastatic LNs but increased the false-negative rate of the assessment by producing false-negative results in patients who would not have undergone a biopsy due to negative AXUS findings.
Assuntos
Neoplasias da Mama , Axila/patologia , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Ultrassonografia de Intervenção/métodosRESUMO
This study was carried out to determine the prevalence and risk factors of genital HPV infection in women diagnosed with non-negative cytology in Southeastern Hungary. Cervical samples were collected for cytology and HPV testing from women seen at gynaecological outpatient clinics and diagnosed with non-negative cytology. The observed overall average HPV infection rate was found to be 61%. A smoking habit was the only risk factor in the logistic regression analysis that related significantly to exposure to HPV infection. Thus, prevention strategies should focus on the regular clinical cytological screening of HPV-infected patients and on the reduction of smoking.
Assuntos
Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Estudos Transversais , Feminino , Humanos , Hungria/epidemiologia , Infecções por Papillomavirus/diagnóstico , Prevalência , Análise de Regressão , Fatores de Risco , Fumar , Esfregaço Vaginal , Displasia do Colo do Útero/diagnósticoRESUMO
The objective of the study in rats was to investigate the anti-inflammatory effects of pure meloxicam (ME) with different particle sizes and of physical mixtures of the binary ME-mannitol system. The level of local inflammation was significantly decreased when the amount of mannitol was the highest and the particle size of ME was the lowest as well as the components had the interparticulate interaction. The same results were achieved in in vitro experiments.
Assuntos
Anti-Inflamatórios não Esteroides/química , Manitol/química , Tiazinas/química , Tiazóis/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Carragenina , Química Farmacêutica , Relação Dose-Resposta a Droga , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Masculino , Manitol/farmacologia , Meloxicam , Tamanho da Partícula , Ratos , Solubilidade , Tiazinas/farmacologia , Tiazóis/farmacologiaRESUMO
BACKGROUND: NOD1/CARD4, a member of the pattern-recognition receptor family, is a perfect candidate as a susceptibility gene for Crohn's disease. Since only limited and conflicting data are available on G796A polymorphisms in inflammatory bowel disease patients, we set out to study the effect of this polymorphism on the susceptibility and course of Crohn's disease in the Hungarian population. METHODS: Four hundred thirty-four unrelated Crohn's disease patients (age at presentation: 28.6+/-9.6 years, female/male: 210/224, duration of Crohn's disease: 8.2+/-6.9 years) and 200 healthy subjects (blood donors) and 136 non-inflammatory bowel disease gastrointestinal controls with chronic gastritis were investigated. NOD1 G796A was detected by using polymerase chain reaction/restriction fragment length polymorphism. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The frequencies of the variant alleles of NOD1 G796A differed significantly between the Crohn's disease patients and both healthy (GG 49.5% vs. 67%; AG 41.5% vs. 28%; and AA 9.0% vs. 5.2%; p<0.0001) and non-inflammatory bowel disease controls with chronic gastritis. Carriage of the single nucleotide polymorphism of NOD1 G796A proved to be a highly significant risk factor for Crohn's disease compared to both healthy (p<0.0001, OR: 2.1, 95% CI: 1.5-2.9) and non-inflammatory bowel disease controls with chronic gastritis (p=0.008). Significant associations were not found between the different genotypes and the demographic data on the patients or the clinical characteristics of Crohn's disease. The different polymorphisms of pattern-recognition receptors (e.g. NOD2/CARD15 SNP8, SNP12 and SNP13 mutations, the TLR4 D299G polymorphism and NOD1 G796A) did not reveal a mutual basis. CONCLUSIONS: Our results suggest that carriage of the NOD1 G796A mutation increases susceptibility for Crohn's disease in the Hungarian population.
Assuntos
Doença de Crohn/genética , Predisposição Genética para Doença , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único , Adulto , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Feminino , Humanos , Hungria/epidemiologia , MasculinoRESUMO
The central corticotropin-releasing factor (CRF)-ergic system plays a critical role in anxiety and other behavioral stress responses. It has been shown that atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides exert anxiolytic-like effects in behavioral studies. Our previous findings demonstrated that various doses of centrally administered ANP selectively altered the CRF content in different brain areas. In the present study, CRF immunoreactivity was determined in hypothalamic and extrahypothalamic brain regions after central injection of BNP or CNP in rats. A high dose (400 ng) of BNP significantly increased the CRF-like immunoreactivity (CRF-LI) in the hypothalamus and amygdala, while only a tendency towards an increase was found in the hippocampus. In the hypothalamus, the CRF-LI decreased after a high dose (400 ng) of CNP. The CRF-LI increased in the basal forebrain after a low dose (100 ng) of CNP. These results suggest that CRF may be involved in the mediation of some neuroendocrine and behavioral responses to BNP and CNP.
Assuntos
Encéfalo/efeitos dos fármacos , Hormônio Liberador da Corticotropina/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Proteínas/farmacologia , Animais , Encéfalo/metabolismo , Injeções Intraventriculares , Masculino , Peptídeo Natriurético Encefálico , Peptídeo Natriurético Tipo C , Proteínas do Tecido Nervoso/administração & dosagem , Proteínas/administração & dosagem , Ratos , Ratos WistarRESUMO
The pathological steroid biosynthesis of a virilizing ovarian tumor was examined via high performance liquid chromatography-radioimmunoassay (HPLC-RIA) determination of the intratissular steroid concentrations. Sex cord-stromal tumor of the ovary was obtained surgically from an 18-year-old female patient with extremely high androst-4-ene-3,17-dione (4-en-dione) and testosterone (Test) blood serum levels. The tissue specimen was extracted with ethyl acetate and the extract was then purified on a C18 mini-column with methanol-water eluents. Steroids were isolated by reversed-phase HPLC on a C18 silica gel column with 51%, 55% and 64% v/v methanol-water eluents. Steroids in the collected eluent fractions were detected by the radioactivity of tritiated internal standards and then quantified by specific RIAs. In the tumor specimen, very high 17alpha-hydroxyprogesterone (17-OH-Prog; 6300 fmol/g), dehydro-epiandrosterone (2870 fmol/g), androst-4-ene-3,17-dione (3000 fmol/g), testosterone (5700 fmol/g) concentrations, and less progesterone (PROG; 320 fmol/g) and androst-5-ene-3beta,17beta-diol (5-en-diol; 320 fmol/g), were determined. Tissue levels of 5alpha-dihydrotestosterone (DHT), 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), 5alpha-androstane-3beta,17beta-diol (3beta-diol), and 17beta-estradiol were found to be 71, 20, 28, and 12 fmol/g, respectively. Steroid profile analysis verified a pathological steroid biosynthesis in the ovarian tumor and suggested that the 17alpha-hydroxylase (17alpha-H), 17,20-lyase (17,20-L), and 3beta-hydroxysteroid dehydrogenase/Delta5-4-isomerase (Delta5-3beta-HSD) activities were particularly elevated in this tumorous tissue. Present data demonstrate that the analysis of intratissular steroid profile by a HPLC-RIA method may valuably contribute to the steroidal pathophysiology of endocrine tumors.
Assuntos
Biomarcadores Tumorais/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Tumores do Estroma Endometrial/metabolismo , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/metabolismo , Neoplasias Ovarianas/metabolismo , Radioimunoensaio/métodos , Virilismo/metabolismo , Adolescente , Tumores do Estroma Endometrial/complicações , Feminino , Humanos , Neoplasias Ovarianas/complicações , Células Tumorais Cultivadas , Virilismo/etiologiaRESUMO
OBJECTIVE: The importance of Chlamydia trachomatis (C. tr.) infection in the etiology of premature labor was examined in a prospective, representative, multicenter study. METHOD: Specimens were collected from 6161 subjects in seven centers and examined by the Gen-Probe method. RESULTS: The infection rate was 5.74%. There were no significant correlations between low birth weight, premature rupture of the membranes, dysmaturity and C. tr. infection. In cases of threatening premature labor, the infection rate was significantly higher in C. tr.-positive patients. In the event of combined low birth weight and perinatal death, the maternal C. tr. infection rate was significantly higher than in normal pregnancies. C. tr.-positive patients treated with roxithromycin had term deliveries. A correlation between poor social circumstances and a high C. tr. infection rate could be proved. CONCLUSION: Cases with a poor obstetric history and/or socially high-risk patients should be screened for C. tr. infection, and in positive cases treatment is recommended.
Assuntos
Infecções por Chlamydia/complicações , Chlamydia trachomatis , Trabalho de Parto Prematuro/microbiologia , Complicações Infecciosas na Gravidez , Antibacterianos/uso terapêutico , Peso ao Nascer , Infecções por Chlamydia/tratamento farmacológico , Feminino , Retardo do Crescimento Fetal/etiologia , Ruptura Prematura de Membranas Fetais/microbiologia , Humanos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Roxitromicina/uso terapêuticoRESUMO
During the first 3 months of the full-time lactation the level of the lipid and lipoprotein fractions does not change in the mother's blood. The levonorgestrel contraceptive pills taken during the lactation do not influence considerably the lipid-metabolism either. There is only one minute deviation in the levonorgestrel group, which is the decreasing though not significant change of the HDL level. The contraceptive pills containing levonorgestrel can be given during the lactation without any danger from the point of view of mother's lipid-metabolism, too.
Assuntos
Aleitamento Materno , Anticoncepcionais Orais Hormonais/farmacologia , Levanogestrel/farmacologia , Lipídeos/sangue , Lipoproteínas HDL/sangue , Lipoproteínas/metabolismo , Adulto , Feminino , HumanosRESUMO
The results of seven gonadotropin releasing hormone (GnRH) loading tests are presented with special respect to the changes of melatonin level. The tests were carried out after a withdrawal bleeding triggered by progesterone (100 mg for 5 days) and plasma FSH, LH, prolactin and melatonin level were determined. The initial melatonin values were between 3.9 and 35.7 pg/ml and were in inverse ratio with the basal gonadotropin levels. In the case of reactive hypophyseal response the melatonin level decreased in every case in inverse ratio with the increase of gonadotropins. In one case, after the GnRH administration there was no increase in gonadotropin production and at the same time the melatonin secretion remained unchanged. According to our examinations the melatonin secretion during the GnRH loading test showed a good correlation with the changes of gonadotropins.
Assuntos
Anovulação/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Melatonina/sangue , Feminino , Hormônio Foliculoestimulante/metabolismo , Humanos , Hormônio Luteinizante/metabolismoRESUMO
Untreated chlamydial infections of the genital tract may cause a wide range of serious complications, which could be prevented by screening. Cost-effectiveness analysis based on previously reported epidemiological study among pregnant women was carried out to develop and evaluate cost-effectiveness of age-based screening (women younger than 20 years old) for Chlamydia trachomatis in Hungary. Three kind of screening strategies were used: a) no screening, b) screening by using ELISA test and c) screening by amplified Gen-Probe diagnostic test. Young age and unmarried status were significant predictors of the chlamydial infection. Prevalence of chlamydial infection was 11.4% in the group of age younger then 20 years. Strategy b) was more cost-effective than neither testing nor treating. Strategy c) was less cost-effective than non screening, unless certain conditions were satisfied. If the cost of the diagnostic test were less or equal than 2,000 HUF or the prevalence of infection in women were greater than 17%, screening strategy c) would be more cost-effective than no screening. Although screening by using ELISA test was more cost-effective than screening by amplified Gen-Probe test, additionally 10,000 infected cases could be prevented using amplified Gen-Probe method for screening Chlamydia trachomatis.
Assuntos
Infecções por Chlamydia/economia , Infecções por Chlamydia/prevenção & controle , Chlamydia trachomatis , Programas de Rastreamento/economia , Adolescente , Adulto , Análise Custo-Benefício , Árvores de Decisões , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hungria , Masculino , Programas de Rastreamento/métodos , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/economia , Complicações Infecciosas na Gravidez/prevenção & controleRESUMO
Invasive intrauterine diagnostic procedures may be followed by feto-maternal transfusion. The authors studied the feto-maternal transfusion after cordocentesis. 199 women underwent fetal umbilical cord blood sampling for fetal karyotyping in weeks 15-26. Maternal serum alpha-fetoprotein level was measured before and after the procedure. The data were statistically analysed by multiple regression analysis and the paired and unpaired Student's t-tests. Twenty percent of more maternal serum alpha-fetoprotein level increase was observed in 73 (36.7%) women. Maximum feto-maternal transfusion was 0.684 ml. The average feto-maternal transfusion was 0.045 ml. No fetal exsanguination was observed. Positive correlation was found between bleeding time after cordocentesis (p = 0.0171) and feto-maternal transfusion as well as the duration of the procedure (p = 0.0275) and feto-maternal transfusion. Negative correlation was found between the amount of fetal blood sample and feto-maternal transfusion (p = 0.0431). The puncture site also influenced feto-maternal transfusion. If the cordocentesis has been performed at the insertion of the cord the feto-maternal transfusion was less than at the free floating umbilical cord (p = 0.0293). Higher feto-maternal transfusion was seen more often after transplacental cordocentesis (p = 0.002). These data suggest that fetomaternal transfusion in the indicator of the difficulty of the procedure.
Assuntos
Cordocentese , Transfusão Feto-Materna , alfa-Fetoproteínas/análise , Feminino , Humanos , Idade Materna , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodosRESUMO
The human papillomaviruses (HPV) are regarded as one of the important agents of cervical carcinoma. A multicentre study was organized to determine the prevalence of HPV in the fertile female population in Hungary. Parallel with the clinical sample collection, a questionnaire interview was performed to acquire data on the life style, socioeconomic status, sexual practice, etc. 1200 women were examined colposcopically and cervix samples were collected for cytology and the detection of HPV DNA. 17.4% of the samples were HPV-infected. 3.9% of the patients had acquired low-risk, and 10.1% 10.2% high-risk HPV types; 3.4% of the women were at the same time infected with both low-risk and high-risk HPV types. Simultaneously performance of cytology and the HPV hybrid capture assay contribute to recognise and treat the precancerous status and risk factors.
Assuntos
Hibridização de Ácido Nucleico , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnósticoRESUMO
The aetiology of childhood acute lymphoblastic leukaemia has been linked with spatially heterogeneous environmental exposures. The presence of spatial clustering would be consistent with geographically localized environmental exposures over long periods of time. The present study is the first to examine spatial clustering amongst children aged 0-4 years using population-based data from Hungary. The data set consisted of 134 children diagnosed with acute lymphoblastic leukaemia who were resident in part of Hungary during the period 1981-2000. Two levels of spatial aggregation were examined: counties and settlements. The Potthoff-Whittinghill and Moran I autocorrelation methods were used to test for spatial clustering. Additionally, an evaluation of the environmental changes during the study period was considered. Specifically analyses were carried out on sub-periods to investigate a possible effect of the Chernobyl catastrophe. There was statistically significant spatial clustering both at the county (estimate of extra-Poisson variation [Formula: see text], P = 0.04) and settlement levels (estimate of extra-Poisson variation [Formula: see text], P = 0.0003). At county level, the finding was attributable to clustering amongst female cases, but at settlement level, the finding was limited to male cases. There was significant spatial autocorrelation in the sub-periods immediately following the accident (1986-1990 & 1991-1995), but not before 1986, nor after 1995. A significant autocorrelation was observed during the 5 year period immediately following the accident (1986-1990, global Moran I = 0.1334, p = 0.005). The centre of significant excesses of ALL cases was located in the county of Baranya. Our study is consistent with an environmental aetiology for acute lymphoblastic leukaemia in children associated with constant exposure to an, as yet unknown, environmental factor in small geographical areas. Although a possible effect of the Chernobyl accident was found in the autocorrelation analysis, the role of chance cannot be excluded.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Pré-Escolar , Análise por Conglomerados , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Feminino , Geografia , Humanos , Hungria/epidemiologia , Lactente , Recém-Nascido , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Características de Residência , Fatores de RiscoRESUMO
BACKGROUND: Some of the most important questions relating to the use of biological therapy in inflammatory bowel diseases concern the duration of maintenance therapy. AIM: To assess the disease course and frequency of relapse of Crohn's disease (CD) following discontinuation of biological therapy, and to determine predictive factors for relapse. METHODS: One hundred twenty-one CD patients who had achieved clinical remission following 1 year of biological therapy and for whom biological therapy was then discontinued participated in this prospective observational study. Eighty-seven CD patients had received infliximab and 34 adalimumab. The definition of relapse was an increase of >100 points in CDAI to at least a CDAI of 150 points. RESULTS: Biological therapy was restarted within 1 year of treatment cessation in 45% of patients. Logistic regression analysis revealed that previous biological therapy (P = 0.011) and dose intensification during the 1-year course of biological therapy (P = 0.024) were associated with the need for and the time to the restarting of biological therapy. Smoking was observed to have an effect that was not statistically significant (P = 0.053). CONCLUSIONS: Biological therapy was restarted a median of 6 months after discontinuation in almost half of Crohn's disease patients in who had been in clinical remission following 1 year of biological therapy. These results suggest that, in the event of the presence of certain predictive factors, biological therapy should probably be continued for more than 1 year by most patients.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/diagnóstico , Adalimumab , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Terapia Biológica/métodos , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Indução de Remissão , Fatores de Tempo , Adulto JovemRESUMO
In situ hybridization, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blot analysis were applied to study the changes in expression of the major nociceptive ion channel transient receptor potential vanilloid type 1 receptor (TRPV1) after the perineural application of capsaicin or nerve transection. In control rats, quantitative morphometric and statistical analyses of TRPV1 protein and mRNA expression in L5 dorsal root ganglion cells revealed distinct populations of small (type C) and small-to-medium (type B) neurons, which showed very high and moderate levels of TRPV1, whereas larger (type A) neurons mostly did not express this receptor. After either transection or capsaicin treatment of the sciatic nerve, immunohistochemistry and Western blotting demonstrated a massive (up to 80%) decrease in the proportion of TRPV1-immunoreactive neurons and TRPV1 protein at all postoperative survival times. In situ hybridization indicated marked decreases (up to 85%) in the proportion of neurons that expressed TRPV1 mRNA after sciatic nerve transection. In contrast, although perineural treatment with capsaicin resulted in similar substantial decreases in the proportions of type B and C neurons of the L5 dorsal root ganglia 3 days postoperatively, a clear-cut tendency to recovery was observed thereafter. Hence, the proportions of both type B and C neurons expressing TRPV1 mRNA reached up to 70% of the control levels at 30 days postoperatively. In accord with these findings, quantitative RT-PCR revealed a marked and significant recovery in TRPV1 mRNA after perineural capsaicin but not after nerve transection. These observations suggest the involvement of distinct cellular mechanisms in the regulation of the TRPV1 mRNA expression of damaged neurons, specifically triggered by the nature of the injury. The present findings imply that the antinociceptive and anti-inflammatory effects of perineurally applied capsaicin involve distinct changes in neuronal TRPV1 mRNA expression and long-lasting alterations in (post)translational regulation.
Assuntos
Gânglios Espinais/patologia , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Neuropatia Ciática/patologia , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Análise de Variância , Animais , Capsaicina/efeitos adversos , Contagem de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Ratos , Ratos Wistar , Neuropatia Ciática/induzido quimicamente , Neuropatia Ciática/etiologia , Fármacos do Sistema Sensorial/efeitos adversos , Fatores de TempoRESUMO
UNLABELLED: The high cost of infliximab inhibits the regular retreatment of all patients in Hungary with Crohn's disease (CD) after beneficial induction therapy. This study is set out to evaluate the medium-term efficacy of induction therapy with infliximab without retreatment in CD patients with chronic activity and/or fistulae refractory to conventional therapy. METHODS: A retrospective 1-year review was undertaken of all CD patients with successfully induced remission or fistula closure with 3 infusions of infliximab. Infliximab was administered in a dose of 5 mg/kg 3 times, in weeks 0, 2 and 6. Clinical remission was defined as symptom resolution and an estimated Crohn's Disease Activity Index (CDAI) <150 and complete fistula closure. We evaluated the clinical response, the estimated CDAI, the number of draining fistulae, the dosages of steroid and immunosuppressive drugs at 6 and 12 months after the last infusion, and the needs for hospitalization and surgical intervention during this period. Breslow (Generalized Wilcoxon) test was used as the statistical method. RESULTS: The data of the 50 patients (19 luminal, 31 fistulizing disease; average age 29. 3 [13-59] years, disease localization: 23 colon, 13 ileum, 13 ileocolon, 1 duodenum) were suitable for analysis. Infliximab induction therapy without retreatment resulted in a beneficial effect lasting for at least 1 year in 22 of the 50 patients (44%). 11 of the 19 patients (57.9%) with luminal disease remained in steroid-free complete remission, while the fistulae persisted closed in only 11 of the 31 patients (35.5%) (p<0.05). CONCLUSION: Infliximab induction therapy alone may result in sustained remission mainly in patients with luminal disease. These results suggest the need for maintenance therapy with infliximab after successful therapy induction in patients with fistulae, while luminal CD patients could possibly participate in regular retreatment only if needed. If these data are confirmed, this modification of the therapeutic procedure could well increase the cost-effectiveness of infliximab.