Assuntos
Ácido Glutâmico/metabolismo , Estresse Psicológico/metabolismo , Sinapsinas/metabolismo , Doença Aguda , Animais , Córtex Cerebral/metabolismo , Corticosterona/sangue , Eletrochoque/efeitos adversos , Masculino , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Ratos , Estresse Psicológico/etiologia , Estresse Psicológico/patologia , Sacarose/farmacologia , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Fatores de Tempo , Trítio/metabolismoRESUMO
BACKGROUND: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. OBJECTIVE: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. METHOD: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. RESULTS: We included 306 patients (85.6% women, mean age 42.3±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17-5.00]; p<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.
Assuntos
Transtornos de Enxaqueca , Disfunções Sexuais Fisiológicas , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Masculino , Prevalência , Estudos Transversais , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/complicações , Fatores de Risco , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Cefaleia/complicaçõesRESUMO
INTRODUCTION: Headache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. DEVELOPMENT: This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. CONCLUSIONS: We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients.
Assuntos
Aleitamento Materno , Neurologia , Feminino , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Humanos , Gravidez , SociedadesRESUMO
OBJECTIVES: There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. METHODS: This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. RESULTS: The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains. CONCLUSIONS: H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Genótipo , Helicobacter pylori/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biópsia por Agulha , Progressão da Doença , Feminino , Mucosa Gástrica/patologia , Gastrite Atrófica/patologia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/microbiologia , Fatores de Risco , Neoplasias Gástricas/microbiologiaRESUMO
BACKGROUND: Migraine attacks have a high impact on daily activities. There is limited research on the burden of migraine on sexual functioning. OBJECTIVE: To determine the prevalence of sexual dysfunction in patients with migraine and its relationship with migraine features and comorbidities. METHOD: This is a cross-sectional study. We included migraine patients between 18 and 60 years-old from 8 Headache Clinics in Spain. We recorded demographic data and migraine features. Patients fulfilled a survey including comorbidities, Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale and a questionnaire about migraine impact on sexual activity. A K-nearest neighbor supervised learning algorithm was used to identify differences between migraine patients with and without sexual dysfunction. RESULTS: We included 306 patients (85.6% women, mean age 42.3±11.1 years). A 41.8% of participants had sexual dysfunction. Sexual dysfunction was associated with being female (OR [95% CI]: 2.42 [1.17-5.00]; p<0.001), being older than 46.5 years (4.04 [2.48-6.59]; p<0.001), having chronic migraine (2.31 [1.41-3.77]; p=0.001), using preventive medication (2.45 [1.35-4.45]; p=0.004), analgesic overusing (3.51 [2.03-6.07]; p<0.001), menopause (4.18 [2.43-7.17]; p<0.001) and anxiety (2.90 [1.80-4.67]; p<0.001) and depression (6.14 [3.18-11.83]; p<0.001). However, only female gender, age, menopause and depression were the statistically significant variables selected in the model to classify migraine patients with or without sexual dysfunction (Accuracy [95% CI]: 0.75 (0.62-0.85), Kappa: 0.48, p=0.005). CONCLUSIONS: Sexual dysfunction is frequent in migraine patients visited in a headache clinic. However, migraine characteristics or use of preventive medication are not directly associated with sexual dysfunction. Instead, risk factors for sexual dysfunction were female gender, higher age, menopause and depression.
RESUMO
INTRODUCTION: When a patient is diagnosed with primary headache or craniofacial neuralgia in the emergency department or in primary care, and is referred to a neurologist due to the complexity of the case, it is useful to know whether additional examination should be sought and the priority (urgent, preferential or normal) with which the patient should be seen. This will avoid unnecessary delays in patients with disabling headache and where organic causes are suspected. In order to issue recommendations on this matter, the Spanish Society of Neurology's Headache Study Group has decided to create a series of agreed recommendations constituting a referral protocol for patients with headache and/or craniofacial neuralgia. DEVELOPMENT: Young neurologists with an interest and experience in headache were invited to draft a series of practical guidelines in collaboration with Spanish Society of Neurology's Headache Study Group Executive Committee. For practical reasons, the document was divided into 2 articles: this first article focuses on primary headaches and craniofacial neuralgias and the second on secondary headaches. In order for the recommendations to be helpful for daily practice they follow a practical approach, with tables summarising referral criteria, examinations to be performed, and referral to other specialists. CONCLUSIONS: We hope to offer a guide and tools to improve decision-making regarding patients with headache, identifying complementary tests to prioritise and referral pathways to be followed, in order to avoid duplicated consultations and delayed diagnosis and treatment.
Assuntos
Serviço Hospitalar de Emergência , Guias como Assunto/normas , Cefaleia/diagnóstico , Neuralgia/diagnóstico , Neurologia , Atenção Primária à Saúde , Encaminhamento e Consulta , Tomada de Decisões , Cefaleia/classificação , Humanos , Sociedades , EspecializaçãoRESUMO
Gastric Cancer (GC) is a complex and heterogeneous disease, which represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still a leading cause of cancer-related death. Over the last decade, several clinical trials have tested novel agents for advanced GC with mostly disappointing results. Heterogeneity, the absence of molecular selection in clinical trials and powerless predictive biomarkers may be potential explanations. Different molecular classification proposals for GC based on the genetic, epigenetic, and molecular signatures have been published. Molecular characterization of GC may offer new tools for more effective therapeutic strategies, such as the development of therapies for specifically well-defined sets of patients as well as the use of new clinical trial designs, which will ultimately lead to an improvement of medical management of this disease. However, the possibilities of implementation of GC molecular classifications on daily practice and their therapeutic implications remain challenging to date. In this review, we will describe and compare these GC molecular classifications, focusing on their main characteristics as the basis for their potential therapeutic implications and strategies for their clinical application. Key Message: A better understanding of gastric cancer molecular characteristics may lead to further improvements in treatment and outcomes for patients with the disease.
Assuntos
Neoplasias Gástricas/classificação , Instabilidade Genômica , Humanos , Estadiamento de Neoplasias , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
INTRODUCTION: Headache is one of the most common neurological complaints, and is most frequent during reproductive age. As a result, we are routinely faced with pregnant or breastfeeding women with this symptom in clinical practice. It is important to know which pharmacological choices are the safest, which should not be used, and when we should suspect secondary headache. To this end, the Spanish Society of Neurology's Headache Study Grouphas prepared a series of consensus recommendations on the diagnostic and therapeutic algorithms that should be followed during pregnancy and breastfeeding. DEVELOPMENT: This guide was prepared by a group of young neurologists with special interest and experience in headache, in collaboration with the Group's Executive Committee. Recommendations focus on which drugs should be used for the most frequent primary headaches, both during the acute phase and for prevention. The second part addresses when secondary headache should be suspected and which diagnostic tests should be performed in the event of possible secondary headache during pregnancy and breastfeeding. CONCLUSIONS: We hope this guide will be practical and useful in daily clinical practice and that it will help update and improve understanding of headache management during pregnancy and breastfeeding, enabling physicians to more confidently treat these patients.
RESUMO
BACKGROUND: The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent. PATIENTS AND METHODS: A nested case-control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin alpha and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured. RESULTS: IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19-4.96] and allele IL1RN Ex5-35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 -251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32-0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B -580C and TNF -487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R -29429T variant was observed (OR 1.74; 95% CI 1.15-2.63). CONCLUSION: This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 -251T>A may modify the risk for GC.
Assuntos
Adenocarcinoma/genética , Citocinas/genética , Neoplasias Gástricas/genética , Adenocarcinoma/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Interleucinas/genética , Linfotoxina-alfa/genética , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Polimorfismo Genético , Estudos Prospectivos , Neoplasias Gástricas/epidemiologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
Hand washing was rightly considered a measure of personal hygiene for centuries. Today there is enough scientific evidence showing that a simple and inexpensive measure can help significantly reduce clinical infections. In spite of this, published studies show that hand hygiene only takes place between 15% and 50% of the instances in which it should be done. In order to support countries in setting priorities to deal with infections related to health care, the World Health Organization has developed a campaign to improve compliance with hand hygiene. Fundamental elements of the campaign include staff training, change of habits, motivating health professionals, and enabling access to effective products at the point of patient care. At institutional level, healthcare managers need to make a firm commitment, and make hand hygiene one of the quality assurance objectives of their organisations.
Assuntos
Prática Clínica Baseada em Evidências , Desinfecção das Mãos/normas , HumanosRESUMO
OBJECTIVE: Levels of tissue factor pathway inhibitor (TFPI) have been associated with arteriosclerosis and thrombotic disease. Although a genetic component to variation in TFPI levels is well-documented, no systematic genome-wide screens have been conducted to localize genes influencing levels of TFPI. METHODS AND RESULTS: We studied TFPI levels in 397 individuals in 21 Spanish families participating in the Genetic Analysis of Idiopathic Thrombosis (GAIT) study. Twelve families were selected through a proband with idiopathic thrombosis and 9 were ascertained without regard to phenotype. A genome scan was performed using microsatellite markers spaced at approximately 10 cM intervals. Standard multipoint variance component linkage methods were used. The heritability of TFPI levels was 0.52 (P<0.0001), with no evidence for shared household effects. In the genome screen, only 1 LOD score >2 was observed. On chromosome 2q, the maximum multipoint LOD score was 3.52 near marker D2S1384. This is near the structural gene for TFPI, which is located at 2q32. In follow-up association analyses, marginal evidence of association (P=0.04) was observed with the TFPI promoter variant C-399T. CONCLUSIONS: These results suggest that polymorphisms in and around the TFPI structural gene may be the major genetic determinants of variation in TFPI levels.
Assuntos
Cromossomos Humanos Par 2 , Lipoproteínas/sangue , Lipoproteínas/genética , Trombose/sangue , Trombose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Genômica , Humanos , Lactente , Escore Lod , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
[This retracts the article DOI: 10.17179/excli2015-642.].
RESUMO
Depressed levels of atheroprotective large HDL particles are common in obesity and cardiovascular disease (CVD). Increases in large HDL particles are favourably associated with reduced CVD event risk and coronary plaque burden. The objective of the study is to compare the effectiveness of low-carbohydrate diets and weight loss for increasing blood levels of large HDL particles at 1 year. This study was performed by screening for body mass index (BMI) and metabolic syndrome in 160 consecutive subjects referred to our out-patient Metabolic Unit in South Italy. We administered dietary advice to four small groups rather than individually. A single team comprised of a dietitian and physician administered diet-specific advice to each group. Large HDL particles at baseline and 1 year were measured using two-dimensional gel electrophoresis. Dietary intake was assessed via 3-day diet records. Although 1-year weight loss did not differ between diet groups (mean 4.4 %), increases in large HDL particles paralleled the degree of carbohydrate restriction across the four diets (p<0.001 for trend). Regression analysis indicated that magnitude of carbohydrate restriction (percentage of calories as carbohydrate at 1 year) and weight loss were each independent predictors of 1-year increases in large HDL concentration. Changes in HDL cholesterol concentration were modestly correlated with changes in large HDL particle concentration (r=0.47, p=.001). In conclusion, reduction of excess dietary carbohydrate and body weight improved large HDL levels. Comparison trials with cardiovascular outcomes are needed to more fully evaluate these findings.
RESUMO
Treatment of etiolated Vicia sativa seedlings by the plant hormone methyl jasmonate (MetJA) led to an increase of cytochrome P450 content. Seedlings that were treated for 48 h in a 1 mM solution of MetJA stimulated omega-hydroxylation of 12:0 (lauric acid) 14-fold compared with the control (153 versus 11 pmol min-1 mg-1 protein, respectively). Induction was dose dependent. The increase of activity (2.7-fold) was already detectable after 3 h of treatment. Activity increased as a function of time and reached a steady level after 24 h. Northern-blot analysis revealed that the transcripts coding for CYP94A1, a fatty acid omega-hydroxylase, had already accumulated after 1 h of exposure to MetJA and was maximal between 3 and 6 h. Under the same conditions, a study of the enzymatic hydrolysis of 9,10-epoxystearic acid showed that both microsomal and soluble epoxide hydrolase activities were not affected by MetJA treatment.
RESUMO
OBJECTIVES: To evaluate the occurrence and define the aetiology of osteopenia in children receiving highly active antiretroviral therapy (HAART). METHODS: Bone mineral density (BMD) of total body and lumbar spine (L2-L4) was assessed by dual-energy X-ray absorptiometry in 40 children vertically infected with HIV: 35 taking HAART and five naive to any antiretroviral treatment (untreated). Six HAART-treated children showed clinical evidence of lipodystrophy. N-terminal propeptide of type-I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and N-terminal telopeptide of type I collagen (NTx) were measured. Results were compared with those obtained in 314 healthy controls. Differences between HIV-positive and healthy children and within the HIV-positive group were assessed by multivariate analyses, controlling for confounding variables (age, sex, weight and height). RESULTS: HAART-treated children showed lower spine BMD values than untreated (P = 0.045) and healthy (P = 0.004) children and lower total body BMD values than untreated (P = 0.012) and healthy (P < 0.0001) children. Spine and total body BMD were similar between untreated and healthy children. Total body BMD was lower (P < 0.005) in HAART-treated children with lipodystrophy than in untreated patients, while children on HAART but without lipodystrophy had intermediate values. BALP, PINP and NTx were similar among untreated and healthy children. HAART-treated children had higher BALP levels than healthy (P = 0.0007) and untreated (P = 0.045) children. PINP values showed the same trend as BALP. HAART-treated children had higher NTx urine levels than healthy (P < 0.0001) and untreated (P = 0.041) children. CONCLUSIONS: HAART seems a new risk factor for life-long osteoporosis in children. An increased rate of bone turnover causes BMD decrease. Severity of osteopenia seems to be related to lipodystrophy.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Densidade Óssea , Doenças Ósseas Metabólicas/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Absorciometria de Fóton , Adolescente , Remodelação Óssea , Reabsorção Óssea , Criança , Pré-Escolar , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Lipodistrofia/induzido quimicamente , MasculinoRESUMO
BACKGROUND: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking. METHODS: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test. RESULTS: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003). CONCLUSIONS: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Composição Corporal/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Lipodistrofia/induzido quimicamente , Absorciometria de Fóton , Tecido Adiposo/patologia , Adolescente , Composição Corporal/fisiologia , Criança , Feminino , Infecções por HIV/patologia , HIV-1/patogenicidade , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
BACKGROUND: The thymus is the organ responsible for the maturation and selection of T lymphocytes and is thus pivotal in allowing the development of a functional immune system. Because in HIV infection cell-mediated immune responses are severely impaired, we studied the role of thymus in the control of the progression of HIV infection to AIDS. METHODS: Thymic volume was analysed by magnetic resonance imaging in 31 vertically HIV-infected children. Plasma HIV viral load and phenotypic and functional cellular immunity-defining parameters were examined in the same patients. RESULTS: Thymic volume was not correlated with age or nutritional status; thymic volume was nevertheless correlated with CD4 T-lymphocyte counts and with the percentage and absolute number of CD45RA+CD62L+ (naive) T lymphocytes. In addition, the ability of peripheral blood mononuclear cells to proliferate upon tetanus stimulation was directly proportional to thymic volume. Finally, a negative correlation was detected between thymic volume and HIV viral load. CONCLUSION: Because low HIV plasma viraemia and preserved immune function are favourable prognostic indices in HIV disease, these data indicate that an immunological, thymic-dependent control of the progression of HIV infection might be possible, at least in vertically transmitted HIV infection.
Assuntos
Infecções por HIV/imunologia , Timo/imunologia , Linfócitos T CD4-Positivos/imunologia , Criança , Progressão da Doença , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Transmissão Vertical de Doenças Infecciosas , Selectina L/imunologia , Antígenos Comuns de Leucócito/imunologia , Imageamento por Ressonância Magnética , Radiografia , Linfócitos T Auxiliares-Indutores/imunologia , Timo/citologia , Timo/diagnóstico por imagem , ViremiaRESUMO
We studied a Spanish family in which one of the female members presented recurrent thrombophlebitis in both legs after three different deliveries. Biological and antigenic activity of protein C was decreased (35% and 42% respectively). Reduced protein C levels were also observed in 6 other family members. Administration of danazol (600 mg/day) in two patients with protein C deficiency elevated this protein and discontinuation of the drug resulted in a reduction of protein C to pretreatment values. The proposita showed a normal fibrinolytic activity and infusion of DDAVP produced a similar response of FVIII/VWF and plasminogen activator to those observed in healthy subjects.
Assuntos
Danazol , Desamino Arginina Vasopressina , Glicoproteínas/deficiência , Pregnadienos , Tromboflebite/sangue , Antitrombina III/análise , Fator X/análise , Feminino , Fibrinólise , Glicoproteínas/análise , Glicoproteínas/genética , Humanos , Masculino , Linhagem , Proteína C , Protrombina/análise , Valores de Referência , Tromboflebite/genéticaRESUMO
Previous studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2.132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinogenemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfibrinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% CI 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% CI 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% CI 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78, 95% CI 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.
Assuntos
Tromboembolia/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Química do Sangue , Causalidade , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Espanha , Tromboembolia/sangue , Tromboembolia/epidemiologia , Tromboembolia/genéticaRESUMO
We studied the effect of purified immunoglobulins (Ig) from 21 patients with antiphospholipid antibodies (aPL) on factor Va degradation by activated protein C (aPC) on cultured human umbilical vein endothelial cells (HUVEC). Sera from patients were tested on an ELISA aPL assay to determine the isotype with aPL activity. HUVEC were incubated with purified IgG or IgM fraction from controls or patients. Activated PC and factor Va were then added and factor Va degradation was measured after several reaction times. 13 of 14 IgM and 8 of 10 IgG from patients showed an inhibitory effect on factor Va degradation by aPC when compared with control Ig. We also observed the same inhibitory effect with patients' Ig on studying the degradation of factor Va by aPC in a purified system containing aPC, protein S and phospholipids. These results suggest that aPL antibodies disturb the anticoagulant activity of aPC, which may contribute to the thrombotic tendency of these patients.