RESUMEN
Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(29-5G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factor-binding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire ABO coding sequence, splice junctions, proximal promoter, and intron 1 enhancer. Amplification products were sequenced by next-generation or Sanger dideoxy methods, either directly or after cloning into a bacterial plasmid vector. Eight unreported alleles were found in the 15 cases analyzed. Alleles ABO*A(28+1C) and ABO*A(295G) harbor variants that alter the consensus sequence at the intron 1 donor and acceptor splice sites, respectively. The other alleles harbor variants that alter the consensus sequence at transcription factorbinding sites in the intron 1 enhancer: specifically, ABO*A(28+5792T), ABO*A(28+5859A), and ABO*A(28+5860G) at GATA-1 sites; ABO*B(28+5877T) and ABO*B(28+5878G) at a RUNX1 site; and ABO*A(28+5843A) at or near a C/EBP site. Molecular and serologic characterization of ABO alleles can help in their future identification and in the resolution of discrepancies.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Sistema del Grupo Sanguíneo ABO/genética , Alelos , Humanos , Intrones , Mutación , FenotipoRESUMEN
Linear IgA bullous dermatosis is an acquired subepidermal immunoglobulin-mediated vesiculobullous disease. In this retrospective, observational, descriptive study, we describe the clinical characteristics, treatments, and outcomes of 17 patients with linear IgA bullous dermatosis. Two children had been vaccinated 2 weeks before the onset of symptoms, 2 had had bronco-obstructive respiratory symptoms, and 1 had received intravenous antibiotic therapy. We also observed an association with autoimmune hepatitis in one patient and alopecia areata in another. One boy had VACTERL association. Diagnosis was confirmed by histopathology and direct immunofluorescence. Sixteen patients were treated with dapsone, which was combined with oral corticosteroids in 8 cases and topical corticosteroids in two. Of note in this series was the occurrence of relapses in the perioral area coinciding with infections and vaccination, and the association between linear IgA bullous dermatosis and autoimmune hepatitis and VACTERL association.
Asunto(s)
Dermatosis Bullosa IgA Lineal , Corticoesteroides/uso terapéutico , Niño , Preescolar , Dapsona/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Femenino , Técnica del Anticuerpo Fluorescente Directa , Humanos , Lactante , Dermatosis Bullosa IgA Lineal/diagnóstico , Dermatosis Bullosa IgA Lineal/tratamiento farmacológico , Dermatosis Bullosa IgA Lineal/etiología , Dermatosis Bullosa IgA Lineal/patología , Masculino , Estudios RetrospectivosRESUMEN
Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.
Asunto(s)
Antígenos de Grupos Sanguíneos/inmunología , Isoanticuerpos/administración & dosificación , Complicaciones Hematológicas del Embarazo/terapia , Isoinmunización Rh/terapia , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Femenino , Sangre Fetal/inmunología , Hemoglobina Fetal/análisis , Humanos , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/inmunología , Complicaciones Hematológicas del Embarazo/prevención & control , Isoinmunización Rh/inmunología , Isoinmunización Rh/prevención & control , Globulina Inmune rho(D)RESUMEN
Skin manifestations have been described in 10-15% of patients with inflammatory bowel disease (Crohn's disease, ulcerative colitis, indeterminate colitis/inflammatory bowel disease type unclassified). There are limited data on the prevalence of these manifestations in paediatric patients, but recent studies have reported its presence in 8% of them at diagnosis. Our aim is to report the different skin manifestations observed in our paediatric patients with inflammatory bowel disease. Case 1: Erythema nodosum at Crohn's disease diagnosis. Typical presentation with painful erythematous nodules in the pretibial region and with good response to infliximab. Case 2: Coexistence of pyoderma gangrenosum and mucocutaneous Sweet's syndrome in a Crohn's disease patient. A rapidly progressive disease that was controlled with systemic steroids but with significant residual lesions. Case 3 and 4: Metastatic Crohn's disease with good response to infliximab.
Asunto(s)
Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades de la Piel/etiología , Adolescente , Niño , Femenino , Humanos , Masculino , Enfermedades de la Piel/patologíaRESUMEN
OBJECTIVES: The intractability of renal dysfunction following thoracic and thoraco-abdominal aortic repair leads us to believe that the accepted mechanisms of renal injury - ischaemia and embolism - are incompletely explanatory. We studied postoperative myoglobinaemia and renal dysfunction following aortic surgery. METHODS: Between September 2006 and February 2008, we studied serum myoglobin in 109 patients requiring thoracic/thoraco-abdominal repair for three postoperative days. Forty-two of the 109 (38%) patients were female. The median age was 67 years (range 23-84 years). As we have focussed more attention on renal function, our independent renal consultants have dialysed more aggressively. We divided dialysis into: (1) creatinine indication, (2) non-creatinine indication and (3) no dialysis. RESULTS: Thirteen of the 109 (12%) patients met creatinine indication for dialysis (>4 mg dl(-1)) and an additional 28 (26%) were dialysed for other reasons. Overall mortality was 12 out of 109 (11%) cases: 11 out of 41 (27%) in dialysed patients and one out of 68 (1.5%) in non-dialysed patients. Mortality did not differ between the indications for dialysis. Predictors of mortality were baseline glomerular filtration rate (GFR), postoperative myoglobin and dialysis. The only predictor of dialysis was postoperative myoglobin. CONCLUSION: A strong relationship between postoperative serum myoglobin and renal failure suggests a rhabdomyolysis-like contributing aetiology following thoraco-abdominal aortic repair. We postulate a novel mechanism of renal injury for which mitigation strategies should be developed.
Asunto(s)
Lesión Renal Aguda/etiología , Aneurisma de la Aorta Torácica/cirugía , Mioglobina/sangre , Rabdomiólisis/complicaciones , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Adulto , Anciano , Anciano de 80 o más Años , Aorta Abdominal/cirugía , Aorta Torácica/cirugía , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Periodo Posoperatorio , Diálisis Renal , Factores de Riesgo , Adulto JovenRESUMEN
The aim of the present study was to determine the paramphistomicidal efficacy of methyl [5-chloro-6-(1-naphthyloxy)-1H-benzimidazol-2-yl]carbamate (alpha-carbamate) in experimentally infected sheep. Sixteen crossbred rams were infected each with 600 metacercariae of Calicophoron calicophorum. Forty five days after infection, they were divided into four groups of four animals each. Groups 1 to 3 received compound alpha-carbamate at a dose of 12, 18, and 24 mg/kg b/w, respectively; group 4 serving as the nontreated control. Ten days after treatment, all animals were killed to obtain the rumen and collect, measure, and quantify the trematodes present. Efficacy was assessed as the percentage of trematode reduction of the treated groups relative to the nontreated control. The obtained efficacy indicated a percentage reduction of 86.7%, 97.5%, and 100% for groups 1, 2, and 3, respectively. This experimental compound showed high efficacy against 45-day-old C. calicophorum in experimentally infected sheep.
Asunto(s)
Antihelmínticos , Bencimidazoles/química , Naftalenos , Enfermedades de las Ovejas/tratamiento farmacológico , Trematodos/efectos de los fármacos , Infecciones por Trematodos/veterinaria , Animales , Antihelmínticos/síntesis química , Antihelmínticos/química , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Bencimidazoles/síntesis química , Bencimidazoles/farmacología , Bencimidazoles/uso terapéutico , Naftalenos/síntesis química , Naftalenos/química , Naftalenos/farmacología , Naftalenos/uso terapéutico , Rumen/parasitología , Ovinos , Enfermedades de las Ovejas/parasitología , Infecciones por Trematodos/tratamiento farmacológico , Infecciones por Trematodos/parasitologíaRESUMEN
BACKGROUND: Red cell (RBC) phenotyping using column agglutination technology (CAT) is currently limited by the reagents formulated in the system. To overcome this limitation, it was investigated whether monoclonal IgM reagents licensed for use with tube tests produced valid results with CAT. STUDY DESIGN AND METHODS: Commercial CAT, does not contain antisera, was used to evaluate Procedures A (40 microL of reagent and 10 microL of 4% RBCs) and B (50 microL of reagent and 50 microL of 0.8% RBCs) with or without incubation at room temperature. In Study 1, reagents were tested to determine whether potentiators inhibit the passage of antigen-negative RBCs through the column. In Study 2, CAT sensitivity was measured by the use of potency titrations to define a procedure for each reagent that matched or exceeded that of the tube method. In Study 3, the specificity of each reagent was determined in parallel with the CAT and tube tests. Typing of 1644 samples was performed. RESULTS: Study 1: Free passage was obtained with all reagents. Study 2: Immediate-spin methods using CAT produced the same results as the tube method. Study 3: With 8048 comparisons made, discrepant results were found in 32 transfused patients and in 6 cord blood samples, mainly with Lewis reagents. With comparison of CAT and the standard tube method, complete agreement was obtained with Kell reagents, 99.9-percent agreement with Kidd reagents, and 98.9-percent and 99.4-percent agreement with Lewis reagents. CONCLUSION: Most examined reagents seem suitable for use with CAT.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Tipificación y Pruebas Cruzadas Sanguíneas/métodos , Pruebas de Hemaglutinación/métodos , Anciano , Anciano de 80 o más Años , Estudios de Evaluación como Asunto , Humanos , Inmunoglobulina M/análisis , Recién Nacido , Sistema del Grupo Sanguíneo de Kell/genética , Sistema del Grupo Sanguíneo de Kell/inmunología , Sistema del Grupo Sanguíneo de Kidd/genética , Sistema del Grupo Sanguíneo de Kidd/inmunología , Antígenos del Grupo Sanguíneo de Lewis/genética , Antígenos del Grupo Sanguíneo de Lewis/inmunología , Fenotipo , Reproducibilidad de los Resultados , VolumetríaAsunto(s)
Dermatitis Atópica/complicaciones , Erupción Variceliforme de Kaposi/complicaciones , Aciclovir/uso terapéutico , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Preescolar , Cloxacilina/uso terapéutico , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Quimioterapia Combinada , Gentamicinas/uso terapéutico , Humanos , Inmunoglobulina E/inmunología , Lactante , Erupción Variceliforme de Kaposi/diagnóstico , Erupción Variceliforme de Kaposi/tratamiento farmacológico , Masculino , Penicilinas/uso terapéuticoAsunto(s)
Síndrome de Down/complicaciones , Tejido Elástico/patología , Enfermedades Cutáneas Papuloescamosas/complicaciones , Enfermedades Cutáneas Papuloescamosas/patología , Adolescente , Antiinflamatorios/uso terapéutico , Biopsia , Niño , Femenino , Humanos , Queratolíticos/uso terapéutico , Ácido Láctico/uso terapéutico , Masculino , Necrosis , Enfermedades Cutáneas Papuloescamosas/tratamiento farmacológico , EsteroidesRESUMEN
BACKGROUND: The epidermal nevus syndromes include different diseases that have the common feature of mosaicism. One of these has been recently identified and named phacomatosis pigmentokeratotica, in analogy to phacomatosis pigmentovascularis. It is characterized by an organoid nevus with sebaceous differentiation, a speckled-lentiginous nevus, and other associated anomalies. It has been hypothesized that this syndrome is caused by a particular genetic mechanism known as the twin-spot phenomenon. OBSERVATIONS: We describe 3 patients manifesting an association of organoid nevus showing sebaceous differentiation and speckled-lentiginous nevus with associated anomalies and update the neurologic findings of a previously described patient. Hemiatrophy seems to be a common finding in all cases; hyperpathia, dysesthesia, and hyperhidrosis, as well as other neurologic defects, may be present. CONCLUSIONS: The findings in these patients allowed us to better delineate this syndrome. Further studies are needed to elucidate the underlying genetic defect. At present, however, the hypothesis that best explains this phenotype is twin spotting. Clinical recognition of this syndrome can contribute to the classification of the epidermal nevus syndromes and give insight into unusual genetic mechanisms occurring in humans.
Asunto(s)
Hamartoma/patología , Nevo Pigmentado/patología , Enfermedades de la Piel/patología , Neoplasias Cutáneas/patología , Adolescente , Adulto , Preescolar , Intercambio Genético , Femenino , Hamartoma/complicaciones , Hamartoma/diagnóstico , Hamartoma/genética , Humanos , Cariotipificación , Masculino , Mutación , Nevo Pigmentado/complicaciones , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/genética , Enfermedades de la Piel/complicaciones , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/genética , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , SíndromeAsunto(s)
Amoxicilina/efectos adversos , Penicilinas/efectos adversos , Psoriasis/etiología , Enfermedad Aguda , Adolescente , Amoxicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Niño , Eritromicina/administración & dosificación , Eritromicina/uso terapéutico , Humanos , Masculino , Penicilinas/uso terapéutico , Psoriasis/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológicoAsunto(s)
Angiomatosis/diagnóstico , Angiomatosis/fisiopatología , Piel/fisiopatología , Diagnóstico Diferencial , Fiebre , Humanos , Lactante , MasculinoRESUMEN
Haemolytic assay for C8 revealed its association in functionally active form with washed human platelets. Platelet-bound C8 haemolytic activity was inhibited by F(ab')2 anti-C8 and was undetectable in the platelet suspension obtained from three C8 deficient patients. Incubation of platelets from C8 deficient individuals in normal plasma did not restore C8 haemolytic activity, indicating that platelets do not absorb C8 from plasma in vitro during platelet preparation. Thrombin, a mediator of the platelet release reaction, did not induce the release of C8 from normal platelets. Conversely, lysis of EAC1-7.9 by platelet bound C8 was not accompanied by release of beta-thromboglobulin or serotonin from the platelets. C8 was detected in a homogenate prepared from platelets as well as in the supernatant collected after high speed centrifugation of the homogenate. The association of C8 with platelets as an individual component rather than as part of the C5b-9 membrane-attack complex was supported by the following evidence: platelet bound C8 eluted from a Sephacryl S-200 column at the same volume as C8 from normal human serum; F(ab')2 anti-C8, but not F(ab')2 anti-C5, inhibited platelet C8 activity; the platelet homogenate, which lysed EAC1-7.9, had no effect on EAC43 which are susceptible to the lytic activity of the C5b-9 complex.
Asunto(s)
Plaquetas/inmunología , Complemento C8/análisis , Complemento C5/inmunología , Complemento C5b , Complemento C8/inmunología , Complemento C9/inmunología , Hemólisis , Humanos , Sueros Inmunes/inmunologíaRESUMEN
Routine laboratory investigations performed on the serum of an 8-year-old girl examined because of a moderate degree of iron-deficiency anemia showed a markedly reduced C3 level. More detailed complement studies revealed a selective C3 deficiency, as indicated by the almost undetectable C3 concentration tested by both hemolytic and immunochemical assays and by the normal or slightly reduced levels of all the other complement components. The hemolytic activity of the serum was restored by the addition of partially purified C3 component. The isolated C3 deficiency could be attributed to the presence of a C3-cleaving activity in the serum of the propositus. This activity was identified as C3 nephritic factor (C3NeF) since it was heat-stable, was absorbed by Cowan I strain of Staphylococcus aureus and was-eluted in the IgG fraction after DEAE-chromatography of the serum. The levels of H and I factors of the alternative pathway in the serum of the propositus and of C3 in the serum samples of her parents and two siblings were found to be within the normal range. The previous clinical history of the girl and the follow-up for a period of approximately 5 years showed that she was apparently healthy and did not reveal clinical and/or laboratory evidence of glomerulonephritis, lipodystrophy or repeated bacterial infections usually associated with the presence of C3NeF in the serum.
Asunto(s)
Factor Nefrítico del Complemento 3/análisis , Complemento C3/deficiencia , Proteínas Inactivadoras de Complemento/análisis , Anemia Hipocrómica/sangre , Quimiotaxis de Leucocito , Niño , Cromatografía DEAE-Celulosa , Electroforesis en Acetato de Celulosa , Femenino , Humanos , Inmunoglobulina G/análisisRESUMEN
Restoration of hemolytic activity was examined in sera from seven unrelated eighth component of complement (C8)-deficient subjects. The sera fell into two groups, depending on whether hemolytic activity was restored by the addition of the beta-chain (group 1) or the alpha-gamma-subunit (group 2) purified from normal human C8. Antigenic analysis of these sera by double-immunodiffusion using anti-human C8 confirmed previous findings of a dysfunctional C8 in the four sera of group 1 and established the presence of a different dysfunctional C8 in one of the sera of group 2 when tested at a high concentration. Further characterization of the dysfunctional C8 molecules in the two sera by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that group 1 sera were missing the beta-subunit and group 2 sera were missing the alpha-gamma-subunit of the C8 molecule. Sera from either of these two groups alone did not produce hemolysis in hemolytic plates containing sheep erythrocytes coated with antibody and complement components up to C7 (EAC1-7) and C9. When sera from the two groups were added to adjacent wells in the hemolytic plates, a zone of hemolysis developed between the wells. The contribution of C8 alpha-gamma from the sera of group 1 and of C8 beta from those of group 2 to the lysis of EAC1-7 in the presence of C9 was confirmed by the inhibitory effect of specific antibodies against the two C8 subunits. In experiments in which hemolytic activity was reconstituted by mixing sera from group 1 with sera from group 2, the serum source of C8 beta (group 2) was the limiting reagent. The dysfunctional C8 molecule in this serum was able to bind to EAC1-7. Chromatographic analysis demonstrated that the generation of hemolytic activity in the mixture of the two sera resulted from the reconstitution of the C8 molecule rather than the sequential action of the two C8 subunits.