RESUMEN
This study aimed to evaluate, improve and compare the performances of two anti-double-stranded DNA (dsDNA) detection kits, differing by their affinity, in discriminating between active and non-active systemic lupus erythematosus (SLE). Eighty-two anti-nuclear antibody positive sera (45 patients) were tested by two anti-dsDNA commercial quantitative assays (Fidis™, Farrzyme™). All the patients fulfilled at least four of the revised American College of Rheumatology criteria. SLE disease activity was assessed using a modified SLEDAI to remove anti-dsDNA descriptors. When using the manufacturers' cut-offs, no difference in the frequency of positive results was found with respect to disease activity, with Fidis™. On the contrary, with Farrzyme™, a significantly higher frequency of positive sera was found in active SLE patients. Nonetheless, poor performances were observed for both tests. With thresholds defined by ROC methodology, 212IU/mL for Fidis™ (Se: 83.9%, Sp: 86.3%), and 68.8IU/mL for Farrzyme (Se: 71.0%, Sp: 96.1%), a great improvement of the accuracy of the two methods was observed. Moreover, the better specificity and pLR, obtained after optimization of the Farrzyme™ test, could also be obtained with the Fidis™ assay by using a higher threshold than that obtained after optimization of the test. We concluded that when using manufacturers' cut-offs, the two assays appeared to be of poor clinical usefulness in the determination of disease activity. A great improvement was observed using higher thresholds. Moreover, a good concordance could be observed between the two assays (κ=0.764).
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Anticuerpos , ADN/sangre , ADN/inmunología , Inmunoensayo/métodos , Lupus Eritematoso Sistémico/sangre , Adolescente , Adulto , Anciano , Anticuerpos/inmunología , Anticuerpos Antinucleares/sangre , Afinidad de Anticuerpos , Niño , Femenino , Humanos , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aß42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. OBJECTIVES: We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia. METHODS: We specifically reduced the phosphorylation level of tau while leaving Aß42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. RESULTS: Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aß42 levels but prevented MCI onset in 10-month-old AAV-AD rats. CONCLUSIONS: The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aß42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aß42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Animales , Disfunción Cognitiva/psicología , Humanos , Fragmentos de Péptidos , Síntomas Prodrómicos , Ratas , Proteínas tau/metabolismoRESUMEN
BACKGROUND: Though our understanding of Alzheimer's disease (AD) remains elusive, it is well known that the disease starts long before the first signs of dementia. This is supported by the large number of symptomatic drug failures in clinical trials and the increased trend to enroll patients at predementia stages with either mild or no cognitive symptoms. However, the design of pre-clinical studies does not follow this attitude, in particular regarding the choice of animal models, often irrelevant to mimic predementia Late Onset Alzheimer's Disease (LOAD). OBJECTIVES: We aimed to pharmacologically validate the AAV-AD rat model to evaluate preventive treatment of AD. METHODS: We evaluated an N-methyl-D-aspartate receptor antagonist, named memantine, in AAV-AD rats, an age-dependent amyloid rat model which closely mimics Alzheimer's pathology including asymptomatic and prodromal stages. Memantine was used at a clinically relevant dose (20 mg daily oral administration) from 4 (asymptomatic phase) to 10 (mild cognitive impairment phase) months of age. RESULTS: A 6-month treatment with memantine promoted a non-amyloidogenic cleavage of APP followed by a decrease in soluble Aß42. Consequently, both long-term potentiation and cognitive impairments were prevented. By contrast, the levels of hyperphosphorylated endogenous tau remained unchanged, indicating that a long-term memantine treatment is ineffective to restrain the APP processing-induced tauopathy. CONCLUSIONS: Together, our data confirm that relevant models to LOAD, such as the AAV-AD rat, can provide a framework for a better understanding of the disease and accurate assessment of preventive treatments.
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Enfermedad de Alzheimer , Tauopatías , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Animales , Humanos , Memantina/uso terapéutico , RatasRESUMEN
Newborn screening for severe combined immunodeficiency (SCID) is now routinely performed in many countries across Europe and around the world. The number of T-cell receptor excision circles (TRECs) reflects T cell levels. TREC quantification is possible using dried blood spot (DBS) samples already collected from newborns to screen for other conditions. This method is very sensitive and highly specific. Data in the literature show that the survival rate for children with SCID is much higher when the disease is detected through early screening, as opposed to a later diagnosis. Newborns diagnosed with SCID may receive the appropriate care quickly, before the onset of serious infectious complications, which raises survival rates, improves quality of life, and limits side effects and treatment costs. At the request of the French Ministry of Health, France's National Authority for Health (Haute Autorité de Santé) is expected to issue recommendations on this topic soon. The nationwide DEPISTREC study, involving 48 maternity units across France, showed that routine SCID screening is feasible and effective. Such screening offers the additional benefit of also diagnosing non-SCID lymphopenia within the infant population.
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Inmunodeficiencia Combinada Grave/diagnóstico , Diagnóstico Precoz , Humanos , Recién Nacido , Tamizaje Neonatal/métodos , Pronóstico , Sensibilidad y Especificidad , Inmunodeficiencia Combinada Grave/mortalidad , Inmunodeficiencia Combinada Grave/terapiaRESUMEN
We report the case of a 5-years old child referred to the pediatric clinic due to a prolonged history of recurrent otitis. Initial immunologic investigation was normal but a severe C3 complement deficiency was detected by the absence of beta 2-globulin protein fraction using serum protein capillary electrophoresis. C3 was not detected in serum and total complement haemolytic activity was decreased. His mother and father had half of the C3 normal plasma level and a heterozygous mutation of the C3 gene. The diagnosis of hereditary deficiency of the third complement component (C3) with compound heterozygous mutation of the gene was made. This defect in complement protein C3, described to date in only 20 families in the world, is associated with repeated infections. The child is treated with oracillin with relatively good control of symptoms.
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Proteínas Sanguíneas/aislamiento & purificación , Complemento C3/deficiencia , Complemento C3/genética , Complemento C3/uso terapéutico , Preescolar , Complemento C3/metabolismo , Femenino , Heterocigoto , Humanos , Inmunoglobulinas/sangre , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Mutación , Otitis/sangre , Otitis/inmunología , Recurrencia , Valores de ReferenciaAsunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Artritis/etiología , Encefalopatías/etiología , Endocarditis Bacteriana/etiología , Enfermedad de Whipple/complicaciones , Anciano , Artritis/sangre , Encefalopatías/sangre , Endocarditis Bacteriana/sangre , Ensayo de Inmunoadsorción Enzimática , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Tropheryma/aislamiento & purificación , Enfermedad de Whipple/sangre , Enfermedad de Whipple/diagnóstico , Enfermedad de Whipple/terapiaRESUMEN
INTRODUCTION: The principal aim of this work was to determine the prevalence of antinuclear antibodies and antinucleosomes antibodies during a treatment by interferon alpha with low dose for 18 months among patients with a melanoma stage I. The secondary objective consisted to seek the existence or not of a correlation with the clinical relapse, to determine the prevalence of appearance of clinical signs of autoimmune diseases and dysthyroidie. PATIENT AND METHODS: It was an exploratory study. The patients included in the study had a melanoma stage I (French classification), whose excision was realized for 6 weeks maximum, with a Breslow index equal or higher than 1,5 mm. The statistical model of logistic regression was used. RESULTS: Eighty-forth patients were included (38 women and 46 men) old from 21 to 75 years. The prevalence of antinuclear antibodies was 39%. None of the following variables: age, sex, phototype, localisation of melanoma in exposed photo zone, index of Breslow or Clark, were significantly associated with the presence of antinuclear antibodies. As the percentage of patients with anti-nucleosomes was low (5%), no statistical study was carried out. The prevalence of clinical and/or biological dysthyroidie was 37%. 60% of the patients presented at a moment in the evolution antinuclear antibodies or a dysthyroidie. The prevalence of relapses and death different was not correlated significantly with antinuclear antibodies and/or a dysthyroidie. DISCUSSION: Many studies report the appearance of antinuclear antibodies, generally without clinical lesions during the treatment by interferon alpha for cancers (tumours carcinoids, hemopathies) and viral chronic hepatitis. Our study is, to our knowledge, the first evaluating the induction of an autoimmunity during the adjuvant treatment by interferon alpha of melanoma stage I. The induction of autoantibody during the treatment by interferon alpha could constitute a marker of effectiveness of the treatment with improvement of the survival of these patients. In our study, however auto immunity markers do not appear as factors of severity of evolution of the melanoma or predictive factors.
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Anticuerpos Antinucleares/sangre , Antineoplásicos/uso terapéutico , Interferón-alfa/uso terapéutico , Melanoma/inmunología , Neoplasias Cutáneas/inmunología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Enfermedades de la Tiroides/inmunologíaRESUMEN
Severe combined immunodeficiencies (SCID) are a group of inherited diseases of the immune system characterized by profound abnormalities of T-cell development. Infants with SCID require prompt clinical intervention to prevent life-threatening infection and studies show significantly improved survival in babies diagnosed at birth based on previous family history. SCID follows the criteria for population-based newborn screening because it is asymptomatic at birth and fatal within the 1st year of life if there is no intervention, the confirmation of the disease is easy, there is a curative treatment, and it is known that early hematopoietic stem cell transplantation significantly improves survival, the quality of immune reconstitution, and quality of life. Quantification of T-cell receptor excision circles (TRECs) in DNA extracted from Guthrie samples is a sensitive and specific screening test for SCID. We conducted a nationwide prospective study of neonatal screening of SCID in a population of 200,000 French newborns over a period of 2 years. The objective was to study the clinical utility and the cost-effectiveness ratio, and to demonstrate that universal SCID screening could result in a substantial benefit to detect individuals, making screening relatively cost-effective in spite of the low incidence of the disease.
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Tamizaje Neonatal , Inmunodeficiencia Combinada Grave/diagnóstico , Análisis Costo-Beneficio , Humanos , Recién Nacido , Tamizaje Neonatal/economía , Estudios ProspectivosRESUMEN
Three sets of experiments were performed to investigate the quality of myeloperoxidase (MPO) preparations and anti-MPO reagents. In the first experiment, two groups of three and four mice were immunized with commercially purified MPO (Calbiochem). Immunization was performed in PBS in the first group and in acetate buffer in the second. From the first group, five monoclonals were raised, and their specificities examined by ELISA and immunoblotting. Surprisingly, these antibodies reacted with lactoferrin (LF) and not MPO. In the second group, 13 monoclonals were raised; six of these reacted with MPO and seven reacted with LF. In a second set of experiments, MPO and LF reactivity were tested in different buffer conditions in the ELISA procedure. Slight variations in the detection of contaminating LF were found. In a third experiment, polyclonal reagents directed against MPO and LF were tested in MPO immunoblotting studies. A polyclonal anti-MPO reagent reacted not only with MPO but also with contaminating material including LF. The anti-MPO polyclonal reagent also reacted with LF on immunoblotting. We conclude that: (i) caution should be exercised when defining anti-neutrophil cytoplasm specificities of human sera and monoclonals by ELISA, (ii) the low concentration of contaminating LF in the commercially purified reference MPO preparation should be taken into consideration since it appears to have high immunoreactivity, (iii) changes in MPO immunoreactivity may occur under different buffer and pH conditions.
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Contaminación de Medicamentos , Lactoferrina/inmunología , Peroxidasa/inmunología , Animales , Anticuerpos Anticitoplasma de Neutrófilos , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Autoanticuerpos/inmunología , Tampones (Química) , Reacciones Cruzadas , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Concentración de Iones de Hidrógeno , Immunoblotting , Ratones , Peroxidasa/aislamiento & purificación , ConejosRESUMEN
The american college of rheumatology (ACR) proposed in 1990 revised clinical criteria for systemic vasculitis classification to define homogeneous group of patients for clinical trials. However, microscopic polyarteritis (MPA) was not clearly identified from polyarteritis nodosa (PAN). Since anti-neutrophil cytoplasm antibodies (ANCA) are markers of disease activity of small vessel vasculitides including MPA, we tested the clinical significance of ANCA in 24 patients with PAN according to the ACR 1990 criteria. Two of 24 patients had ANCA, as defined by indirect immunofluorescence on normal human neutrophils, antigen-specific ELISA and Western blot analysis. However, they exhibited histologically proven small vessel but not medium vessel vasculitis. Furthermore, they had neither artery microaneurysms nor large organ injury consequent upon large vessel occlusion. Although they satisfied ACR criteria for PAN, they probably were misclassified and should be considered as MPA. We conclude that: (i) ANCA are not found in patients with classical PAN in the absence of MPA features; (ii) caution should be exercised when defining PAN according to the ACR 1990 criteria; (iii) ANCA may help systemic vasculitis classification.
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Autoanticuerpos/sangre , Citoplasma/inmunología , Neutrófilos/inmunología , Poliarteritis Nudosa/inmunología , Vasculitis Leucocitoclástica Cutánea/clasificación , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Anticitoplasma de Neutrófilos , Biomarcadores/sangre , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Epítopos/análisis , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Poliarteritis Nudosa/sangre , Vasculitis Leucocitoclástica Cutánea/sangre , Vasculitis Leucocitoclástica Cutánea/inmunologíaRESUMEN
We studied the usefulness of monitoring antineutrophil cytoplasmic antibodies (ANCA) in chronic graft-versus-host disease (cGVHD), a major complication of allogeneic bone marrow transplantation. Antigen-specific ELISA and indirect immunofluorescence (IIF) were used to search for ANCA in 47 allogeneic bone marrow graft recipients who developed cGVHD and in 43 who did not (controls). Eight patients exhibited ANCA IIF positivity in the cGVHD group, but none in the controls. Specificity was confirmed in antigen-specific assays in only two cGVHD patients, both showing antilactoferrin (anti-LF) activity. One of these patients was followed-up, and the antilactoferrin antibodies were found only at the time of active but limited cGVHD. Among three ANCA IIF-positive patients, two had antinuclear autoantibodies and three antineutrophil alloantibodies secondary to blood transfusion, which may have been responsible for false ANCA IIF positivity. It is concluded that ANCA determination is not useful in patients with cGVHD. Polyclonal activation of B lymphocytes could result in ANCA activity during cGVHD. False-positive ANCA could be due to allo-immunization following blood transfusion. Rare patients may present antilactoferrin antibodies of unknown clinical significance.
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Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Trasplante de Médula Ósea/efectos adversos , Enfermedad Injerto contra Huésped/inmunología , Adolescente , Adulto , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Humanos , Masculino , Persona de Mediana Edad , Monitorización Inmunológica , Valor Predictivo de las Pruebas , Trasplante HomólogoRESUMEN
OBJECTIVE: For rheumatoid arthritis (RA), antiperinuclear factor (APF) is as efficient a marker as rheumatoid factor (RF). However, the prevalence and significance of APF of the IgA isotype in active RA, as well as its correlation with RF-IgA, have not been determined. Our goal was to obtain information on these points. METHODS: APF-IgA were screened in 80 sera from patients with active RA, prospectively and consecutively selected over an 8-month period. Sera from 22 patients with Sjögren's syndrome and 50 with lupus were also studied retrospectively for APF-IgG and IgA. RESULTS: APF-IgA were found at a 1:10 dilution or above in 31 RA sera (39%), which were all positive for APF-IgG as well at higher titers. In the 64 sera positive for APF no correlations were found between APF-IgA and IgA or immune complexes-IgA, latex, the Rose-Waaler test and RF-IgA. Conversely, an association of APF-IgA was found with both APF-IgG (p < 0.0001) and anti-stratum corneum of rat esophagus (ASC)-IgG (p < 0.0001). APF-IgA, though correlated with the presence of secondary sicca syndrome in RA (p = 0.0023), was not more frequent (5/22) in primary Sjögren's sera. CONCLUSIONS: RF-IgA and APF-IgA are not correlated. Despite its localization in the mucosae, the target antigen for APF elicit fewer IgA antibodies in RA than does the RF target.
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Anticuerpos Antinucleares/inmunología , Artritis Reumatoide/inmunología , Adulto , Anciano , Animales , Biomarcadores/sangre , Femenino , Proteínas Filagrina , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Proteínas de Filamentos Intermediarios/análisis , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Mucosa Bucal/patología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Ratas , Ratas Wistar , Estudios Retrospectivos , Factor Reumatoide/inmunología , Síndrome de Sjögren/metabolismoRESUMEN
OBJECTIVES: Alpha1-antitrypsin (alpha1-AT) is encoded by a highly polymorphic gene with over 75 codominantly expressed alleles at the protease inhibitor (Pi) locus classified as normal, deficient, dysfunctional or null. The aim of this study was to determine in patients with inflammatory bowel disease: (i) the prevalence of anti-neutrophil cytoplasmic auto-antibodies (ANCA) and their antigen specificities; (ii) alpha1-AT Pi phenotypes; and (iii) possible associations between ANCA, disease activity and deficient alpha1-AT alleles. DESIGN: Study of 95 consecutive patients with ulcerative colitis (UC) and 63 patients with Crohn's disease (CD). METHODS: Diagnosis and disease activity were determined by clinical, endoscopic and histological criteria. ANCA by indirect immunofluorescence (IIF) and Pi phenotyping by isoelectric focusing were performed for all patients. Positive IIF sera were tested in antigen-specific enzyme-linked immunosorbent assay: proteinase 3 (PR3), myeloperoxidase (MPO), lactoferrin (LF), lysozyme, human leucocyte elastase (HLE), cathepsin G and bactericidal/permeability increasing protein (BPI). RESULTS: Sixty-one patients with UC (64.2%) and only 11 with CD (17.5%) had ANCA (P < 0.001). Antigen specificities were PR3 (7/61), MPO (3/61), LF (6/61), HLE (1/63) and BPI (10/61) in UC, and PR3 (2/11) and BPI (2/11) in CD. Three PiZ alleles were found, matching the prevalence in the normal French control population. No relationship was found between the presence of ANCA, antibody specificity, disease activity and deficient alpha1-AT alleles. CONCLUSION: ANCA are more frequent in UC than CD and do not correlate with disease activity. ANCA and protease/antiprotease imbalance do not appear to modulate the clinical course of inflammatory bowel disease.
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Anticuerpos Anticitoplasma de Neutrófilos/sangre , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/inmunología , alfa 1-Antitripsina/genética , Alelos , Especificidad de Anticuerpos/inmunología , Sitios de Unión/genética , Colitis Ulcerosa/genética , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/genética , Enfermedad de Crohn/inmunología , Ensayo de Inmunoadsorción Enzimática , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Focalización Isoeléctrica , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To study the impact of an original education program on compliance to hormone replacement therapy (HRT) in post-menopausal women. METHODS: Data were obtained from 1,192 post-menopausal women (age: 53 +/- 5 years) included in the study with an onset less than six months: E2 gel (n = 791) or patch (n = 401) + progestins, and randomized in either educational program (Ep = 600) or regular verbal counselling (VC = 592). A patient is considered bad compliant with HRT when she prematurely stopped the study, whatever the reason of the cessation. The groups EP and VC are homogeneous for the age distribution, the HRT regimen, the date of onset and the climateric symptoms scores. RESULTS: There is a significant difference between EP and VC groups in compliance, respectively 86 and 81% (p < 0.027). This difference is partially explained by the significant improvement in the patch subgroups (EP: 86% versus VC: 77%, p = 0.028). The trend observed in the gel group is not significant (EP: 85% and VC: 82%) due to the high level of compliance usually noticed in women treated with the gel and the verbal counselling. The significative difference in the compliance observed during the verbal counselling between the continuous (76%) and the sequential (86%, p = 0.001) HRT regimen disappears with the educational program (continuous: 84% and sequential: 87%, NS). CONCLUSION: This first large study on the HRT compliance in France, using a patient educational material, validates its efficacy to reach a better compliance than with regular verbal counselling. Even though in the daily practice, about 40% of the patients discontinue the treatment during the first year, 81% of the women followed in this study continue to receive the HRT after nine months of use. The original educational program of the COMET study improves significatively this high compliance (+ 5% from the verbal counselling). Thus, the combination of the doctor verbal counselling and an educational material is desirable to obtain a good compliance with HRT.
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Terapia de Reemplazo de Estrógeno , Cooperación del Paciente , Educación del Paciente como Asunto , Posmenopausia , Femenino , Francia , Humanos , Persona de Mediana EdadRESUMEN
Antiphospholipid antibodies (antiprothrombinase and anticardiolipin) carry with them for mothers the risks of repeated fetal loss and of disorders of the blood clotting mechanism both before and after delivery. All the same screening does not have to be carried out routinely but should be reserved for patients who have already lost one fetus (intrauterine death after 12 weeks of amenorrhoea) and/or venous or arterial thrombosis. The diagnosis depends on a strict methodology and strict criteria for making a positive diagnosis. The treatment of these antibodies (with corticosteroids and intravenous immunoglobulin) or the prevention of possible thrombotic complications (using platelet antiaggregation/heparin) has to be decided taking into account the level of antibodies, previous obstetric and thrombotic history and the lupus symptomatology as shown by the patients. The overall success rate of treatment is between 53 and 81%.
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Síndrome Antifosfolípido , Complicaciones del Embarazo , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/epidemiología , Síndrome Antifosfolípido/fisiopatología , Síndrome Antifosfolípido/terapia , Aspirina/uso terapéutico , Femenino , Heparina/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Tamizaje Masivo , Prednisona/uso terapéutico , Embarazo , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/terapia , Resultado del EmbarazoRESUMEN
OBJECTIVE: The purpose of this study was to investigate the restoration of immune function in patients given two nucleoside-analogs and one non-nucleoside-analog (nevirapine). PATIENTS AND METHODS: The study was carried out in 27 HIV-1-infected patients, starting a treatment with d4T, ddl and nevirapine, included in the VIRGO trial and followed up to 52 weeks. RESULTS: Total CD4 T cells increased as early as the fourth week of treatment (+154/microliter, p < 0.001) with a gain maintained until week 52 (+201/microliter at week 52). A similar pattern was seen for memory CD4 T cells (+80/microliter at week 4, +110/microliter at week 52). The rise in naive CD4 T cells was slower, strongly significant for week 16 (p < 0.001) and maximum at week 24 (+105/microliter). DISCUSSION: In our study, rise in T cells was not correlated with virological response, however increase in total and naive CD4 T cells was correlated with the CD4 count at onset of therapy (p < 0.05). Our data indicate that patients on d4T-ddl-nevirapine therapy have the same immune restoration as patients given protease inhibitor-based regimens.
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Fármacos Anti-VIH/administración & dosificación , Didanosina/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Nevirapina/administración & dosificación , Estavudina/administración & dosificación , Adulto , Fármacos Anti-VIH/efectos adversos , Recuento de Linfocito CD4 , Didanosina/efectos adversos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , Humanos , Memoria Inmunológica/efectos de los fármacos , Recuento de Linfocitos , Masculino , Nevirapina/efectos adversos , Proyectos Piloto , Estavudina/efectos adversos , Carga ViralRESUMEN
Autoimmune neutropenias (AIN) are classically divided into primary AIN and secondary AIN. The latter are associated with autoimmune disorders, hematologic malignancies, primary immune deficiencies, drug exposure or infections. In this review we will focus on the major aetiologies of AIN, their differential diagnosis, the various methods in biological diagnosis, and the treatment.