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[18F]FDG-PET is a widely used technique for specific evaluation of disease and treatment response in oncology. However, the principles behind [18F]FDG-PET imaging allow a wide-ranging array of benign and malignant pathologies to be identified on both initial and routine surveillance imaging. This is important for clinicians and radiologists, alike, in that effective and accurate evaluation of malignancy and metastatic disease, specifically involving the spine and central nervous system, is crucial. In this article, we review the normal and posttherapy appearance of the spine on [18F]FDG-PET, the various types and patterns of metastatic disease that involve the spine and spinal cord, and, finally, important spinal pathologies that may mimic malignancy on [18F]FDG-PET.
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Neoplasias Primarias Secundarias , Neoplasias , Fluorodesoxiglucosa F18 , Humanos , Tomografía de Emisión de Positrones/métodos , Radiólogos , Radiofármacos , Médula EspinalRESUMEN
The adult intestine hosts a huge number of diverse bacterial species, collectively referred to as the microbiome, that reside mainly in the lower gut, where they maintain a symbiotic relationship with their host. Recent research points to a central role of the microbiome in many biological processes. These microbial communities are influenced by multiple environmental and dietary factors and can modulate immune responses. In addition to local effects on the gastrointestinal tract, the microbiota is associated with effects on other organs and tissues, such as the skin. Indeed, an altered microbiome has been associated with skin disorders in several instances. Thus, in this review, we describe the recent advances regarding the interplay between gut microbiota and the skin. We explore how this potential link affects skin homeostasis and its influence on modulating the cutaneous immune response, focusing on psoriasis disorder. Finally, we discuss how to take advantage of this interplay to manage this disorder, particularly through probiotics administration. In the gastrointestinal tract, the microbiome has been proven to be important in the maintenance of the balance between effector T cells and regulatory T cells, and the induction of immunoglobulin A. Moreover, gut bacterial dysbiosis is associated with chronic inflammatory disorders of the skin, such as psoriasis. Thus, the microbiome can be considered an effective therapeutical target for treating this disorder. Despite some limitations, interventions with probiotics seem promising for the development of a preventive therapy by restoring altered microbiome functionality or as an adjuvant in specific immunotherapy.
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Our study aims to observe the levels of knowledge, attitude, and practice (KAP) associated with sickle cell disease (SCD) and premarital genetic counseling (PMGC) in 351 Saudi adults. The relationships between KAP levels and sociodemographic characteristics (age, gender, marital status, and educational level) were observed. The study was conducted in King Khalid University Hospital between February 21, 2017, and March 7, 2018. A total of 351 Saudi participants attending the primary care clinic were selected using convenience sampling and were given a self-administered questionnaire. Overall, the 351 participants had the best attitude (41% scoring "good"), followed by knowledge (28.8%), and, lastly, practice (19.1%). Out of the sociodemographic characteristics, age group was the most statistically significant in all the three categories (knowledge, attitude, and practice). The > 50-year age group performed the worst in all the three categories. Despite the advancements in public healthcare measures in Saudi Arabia, our study revealed that there are still many gaps to be filled regarding the knowledge, attitude, and practice associated with SCD and PMGC.
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BACKGROUND: Several authors have indicated that there are specific poor prognostic factors which may affect the outcome of management of phalangeal neck fractures. In the authors' centre, phalangeal neck fractures with any of these poor prognostic factors are labelled "troublesome". Any of the following five criteria will qualify the fracture to be regarded as "troublesome": concurrent vascular compromise of the fractured digit, open/partial amputation injuries, comminution of the fractured phalangeal head, concurrent epiphyseal or juxta-epiphyseal fractures distal to the fractured phalangeal head, and all Type III fractures (as per Al-Qattan classification). METHODS: The effect of these poor prognostic factors has not been investigated in the youngest paediatric age group; the hands of whom are known to be most forgiving. The purpose of this study is to compare the outcome of management of seven "troublesome" vs nine "non-troublesome" phalangeal neck fractures in children less than 2 years of age. Demographic data (age, sex, fracture site/type, and troublesome factors) were reviewed for the 16 cases. All patients were treated according to a specific protocol, and the outcome was documented using a modified Al-Qattan's outcome grading system. RESULTS: Of the nine children with non-troublesome fractures, eight obtained a satisfactory outcome and the ninth case had an unsatisfactory outcome. In contrast, all seven children with troublesome fractures had an unsatisfactory outcome and the difference was highly significant (p = 0.0007). CONCLUSION: The authors strongly advise discussing the outcome of troublesome fractures with the parents and also advise documenting this in the file (prior to management) for medico-legal reasons.
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Falanges de los Dedos de la Mano/lesiones , Fracturas Óseas/terapia , Femenino , Humanos , Lactante , Masculino , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: The inflammatory process in the post-appendectomy period is not well characterized. In a pilot study, we prospectively followed the kinetics of different inflammatory mediators before and after appendectomy in children, and compared the results of the groups open appendectomy (OA) and laparoscopic appendectomy (LA). MATERIAL AND METHODS: Levels of sP-selectin, tPA, MCP-1, IL-6, IL-8, sVCAM-1, and sCD40L were measured before appendectomy and on the next three consecutive days in the serum of 25 children (16 males and 9 females) aged 7 - 16 years (mean 12.6+/-2.47 years) with non-perforated acute appendicitis. RESULTS: LA and OA were performed in 16 and 9 patients respectively. None of the markers of inflammation differed significantly by surgical approach at any point of observation. However, sP-selectin, MCP-1 and sVCAM-1 levels were found to have significantly different postoperative kinetics with a trend towards higher values in the laparoscopic group compared to the open appendectomy group (p=0.034, p=0.016 and p=0.025, respectively). CONCLUSIONS: The cytokines sP-selectin, MCP-1 and sVCAM-1 may play a role in the possible post-appendectomy cytokine activation after non-perforated appendicitis. Since this phenomenon is more evident after LA than after OA, the contribution of the different LA procedures has to be further investigated.
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Apendicectomía/efectos adversos , Apendicitis/cirugía , Citocinas/sangre , Inflamación/etiología , Adolescente , Biomarcadores/sangre , Ligando de CD40/sangre , Niño , Femenino , Humanos , Inflamación/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Laparoscopía , Masculino , Proteína Cofactora de Membrana/sangre , Selectina-P/sangre , Proyectos Piloto , Estudios Prospectivos , Activador de Tejido Plasminógeno/sangre , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
AIM: To determine whether implementation of criteria for performing a toxicology screen and increasing staff awareness improve detection of substance abuse among adolescents presenting to the emergency department. METHODS: Patients 12 to 18 years of age presenting to one of three emergency departments in Israel were included in a prospective cohort study. In the 'study' hospital, a set of criteria for urine toxicology screen and measurements of ethanol serum level were implemented. No specific interventions were implemented in the two other hospitals. The main outcome measure was the rate of substance abuse detection. RESULTS: The number of adolescents seen in the participating centres was 3200 at the study hospital, and 3493 and 2792 at the two other hospitals. High blood ethanol concentrations were found in 49 patients at the study hospital compared with 30 and 19 patients at the two other hospitals (p < 0.001). Illicit drugs were detected in 13, 4 and 1 patients, respectively (p = 0.002). CONCLUSIONS: Introducing structured guidelines for ordering toxicological screening increases the detection of alcohol and drug of abuse among adolescents presenting to paediatric emergency departments.
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Alcoholismo/diagnóstico , Servicio de Urgencia en Hospital , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/diagnóstico , Adolescente , Conducta del Adolescente , Intoxicación Alcohólica/diagnóstico , Alcoholismo/epidemiología , Análisis de Varianza , Niño , Etanol/sangre , Etanol/toxicidad , Femenino , Humanos , Drogas Ilícitas/toxicidad , Israel/epidemiología , Masculino , Guías de Práctica Clínica como Asunto , Prevalencia , Estudios Prospectivos , Detección de Abuso de Sustancias/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Orina/químicaRESUMEN
BACKGROUND: The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data on the natural history of this syndrome. OBJECTIVE: To describe the presentation, clinical course, doctors' awareness, therapeutic response and long-term follow-up of children with PFAPA syndrome. METHODS: Children with PFAPA syndrome referred over a 5-year period (from January 1999 to January 2004) were enrolled in the study. Data were gathered from medical records, parents' interviews, physical examination and telephone calls. RESULTS: 54 patients with PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain (65%) and a lower rate of aphthous stomatitis (39%) than those in previous reports. Four different patterns of disease evolution were identified, including the relatively common (n = 14, 26%) and newly described course of alternating remissions and relapses. The remissions lasted 8.5 months on average (range 4-36 months). Diagnosis was established by primary paediatricians in 30 of 54 (56%) patients. However, a substantial delay in diagnosis was apparent (mean 15 months). Episodes were curtailed by a much lower dose of prednisone or equivalent corticosteroid (mean 0.6 mg/kg/day, range 0.15-1.5 mg/kg/day) than reported previously. Tonsillectomy was successful in the prevention of recurrence of further episodes in all six patients who underwent the procedure. CONCLUSIONS: We describe several new characteristics of PFAPA syndrome in children, contributing to our knowledge of this relatively unrecognised but troublesome syndrome. Early diagnosis and appropriate treatment can markedly improve the quality of life of both patients and families.
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Fiebre , Linfadenitis , Faringitis , Estomatitis Aftosa , Corticoesteroides/uso terapéutico , Edad de Inicio , Preescolar , Femenino , Fiebre/terapia , Humanos , Lactante , Linfadenitis/terapia , Masculino , Satisfacción del Paciente , Faringitis/terapia , Recurrencia , Estomatitis Aftosa/terapia , Síndrome , TonsilectomíaRESUMEN
It has been recently shown that mutations in both of the recombination activating genes RAG1 and RAG2 are involved in each of the two different types of severe combined immunodeficiency (SCID) syndromes: T-B- SCID and Omenn's syndrome (OS). The objective of the study was to search for novel mutations in the RAG genes and to offer prenatal diagnosis for families that have been identified as at risk of T-B- SCID or OS. Mutation analyses of polymerase chain reaction products of RAG1/RAG2 genes were performed in 14 cases (T-B- SCID = 6 and OS = 8). Consanguinity was reported in seven (50%) families. Four missense mutations in the RAG2 gene in six of eight OS patients and in four of six T-B- SCID patients were detected. The C1845T transition leading to a Tre215Ile substitution is a novel mutation. All but one of the patients were homozygous for the detected mutations, possibly reflecting the consanguinity in these families and the relative rarity of the disease-causing mutations. In addition, three putative polymorphic sites were found. Prenatal diagnosis was offered to seven families, but three of them declined genetic counseling for religious reasons. In the remaining families, four pregnancies were successfully completed, and in one case, the family chose to have an abortion because of a homozygous mutation. Mutations in RAG1/RAG2 genes were detected in only some of the T-B- SCID or OS patients, and the molecular basis for the remaining cases has yet to be elucidated. Important factors such as religious beliefs need to be considered when offering prenatal diagnosis to certain families.
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Proteínas de Unión al ADN/genética , Proteínas de Homeodominio/genética , Mutación Missense , Diagnóstico Prenatal , Inmunodeficiencia Combinada Grave/genética , Adulto , Consanguinidad , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Homocigoto , Humanos , Masculino , Proteínas Nucleares , Polimorfismo Genético , Embarazo , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/psicología , Religión , Inmunodeficiencia Combinada Grave/diagnósticoRESUMEN
The goal of this study was to identify and characterise the major allergen(s) of sesame seed. Detection of specific IgE to sesame proteins was performed with Pharmacia CAP System and Western blotting, after separation of sesame proteins by SDS-PAGE, using sera from 28 subjects diagnosed as allergic to sesame. The major allergen was separated by gel filtration chromatography and identified by selective proteolysis followed by peptide sequence analyses, employing electrospray-ionization mass spectrometer. Twenty-four of the 28 subjects had sesame-specific IgE. A 14 kDa protein belonging to the 2S albumin family was recognised by 22 of the 24 sera used. Subjecting the 14 kDa after HPLC separation to proteolysis with Lys C yielded 3 peptides, but only one reacted positively in the dot blot test. This peptide, corresponds in the whole protein chain to residues 24-94. The reactivity of the 14 kDa protein with most of the sera indicates that this is the major sesame allergen, later identified as 2S albumin precursor; and its peptide which reacted positively in the dot blot test evidently contains an epitope(s). Some minor sesame allergens, of higher molecular weight, were also revealed.
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Albúminas/análisis , Alérgenos/análisis , Hipersensibilidad a los Alimentos/inmunología , Inmunoglobulina E/análisis , Proteínas de Plantas/análisis , Semillas/inmunología , Sesamum/inmunología , Adolescente , Adulto , Albúminas/inmunología , Alérgenos/inmunología , Secuencia de Aminoácidos , Western Blotting , Niño , Preescolar , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Humanos , Inmunoglobulina E/inmunología , Lactante , Datos de Secuencia Molecular , Proteínas de Plantas/inmunología , Sesamum/químicaRESUMEN
Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response.
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Infecciones por Echovirus/epidemiología , Meningitis Aséptica/epidemiología , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Niño , Preescolar , Infecciones por Echovirus/terapia , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Israel/epidemiología , Masculino , Meningitis Aséptica/terapia , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of this study was to assess the direct medical burden and work loss associated with uncomplicated chickenpox in Israel. METHODS: A total of 155 otherwise healthy children and adolescents with chickenpox were recruited from 10 physician offices in central Israel. Direct and indirect medical burdens were determined by caregiver interview. RESULTS: Mean age was 3.3 +/- 2.3 years. 51% of the patients were under three years of age. Each patient made on average 1.15 visits to a general practitioner. Most patients were taken to the Doctor's office only once during the illness while 23 patients (15%) were seen twice. Three patients were referred to the emergency room. Antihistamines (39%) and Calamine lotion (28%) were the most frequently prescribed medications, followed by acyclovir (17%) and antibiotics (6%). Following the patient's illness there were 72 cases of secondary spread of varicella to household members. The individuals who cared for the child missed a combined total of 2.5 days from work (on average per varicella episode). CONCLUSIONS: Israeli children acquire chickenpox at a younger age than children in North America and England and consume more prescribed medications. While the work loss in the present study was comparable to previous reports, the direct medical costs inflicted by this infection in Israel are not negligible even for uncomplicated cases.
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Varicela/economía , Varicela/epidemiología , Costos de la Atención en Salud , Adolescente , Cuidadores/economía , Varicela/tratamiento farmacológico , Varicela/transmisión , Niño , Preescolar , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Lactante , Israel/epidemiología , Masculino , Visita a Consultorio Médico/estadística & datos numéricos , Embarazo , Factores de Tiempo , TrabajoRESUMEN
OBJECTIVE: To determine the prevalence, importance, and the order of frequency of IgE-mediated food allergens among infants and young children in Israel. STUDY DESIGN AND PATIENTS: In a cross-sectional study, the prevalence of IgE-mediated food allergy was investigated in 9070 infants and young children (0-2 years) who were followed-up at 23 Family Health Centers (FHCs) in central Israel. Patients with suspected IgE-mediated food allergic reactions, were recruited for further evaluation (detailed questionnaire and skin-prick test (SPT)). RESULTS: We identified 150 out of 9070 (1.7%) patients with suspected IgE-mediated food allergy. Among them, 102/150 (67%) [59 males, 43 females; mean age 10.3 months] completed a detailed questionnaire and underwent SPT. Evaluation revealed 131 positive SPTs in 78/102 (76.5%) patients. Twenty-seven positive SPTs in 18 patients were considered clinically irrelevant based on previous consumption of the relevant foods without clinical symptoms. Thus, there were 104 relevant positive SPTs in 78 patients. The overall prevalence of clinically relevant IgE-mediated food allergic reactions among these patients is estimated to be 1.2% (104/9070). The most common food allergens were egg, cow's milk, and sesame. Anaphylaxis was the presenting symptom in 14/78 (18%) including six sesame-induced cases. A history of other atopic diseases was reported in 27 (35%) patients. In addition, 22 (28%) had a history of atopy in first-degree family members. CONCLUSIONS: We found sesame to be a major cause of IgE-mediated food allergy in Israel. In fact, it is second only to cow's milk as a cause of anaphylaxis. We recommend that testing for food allergens be tailored to each community based on local experience and should include sesame in appropriate populations.
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Hipersensibilidad a los Alimentos/epidemiología , Hipersensibilidad a los Alimentos/etiología , Aceite de Sésamo/efectos adversos , Protección a la Infancia , Preescolar , Estudios Transversales , Salud de la Familia , Femenino , Estudios de Seguimiento , Hipersensibilidad a los Alimentos/diagnóstico , Humanos , Lactante , Bienestar del Lactante , Recién Nacido , Israel/epidemiología , Masculino , Prevalencia , Índice de Severidad de la Enfermedad , Pruebas Cutáneas , Encuestas y CuestionariosRESUMEN
AIMS: To evaluate the usefulness of a diluted, inactivated solution of attenuated varicella vaccine in predicting susceptibility to varicella and its correlation with specific antibody titre to varicella. METHODS: In a prospective blinded study, 63 healthy subjects (aged 2-43 years) were studied. Skin test solution was prepared from vials of OKA strain virus which was inactivated by exposure of the vials to room temperature for 10 days; solution was diluted at 1/50 with normal saline and kept at 4 degrees C until used for skin testing. The material was injected intradermally. Serum samples were drawn prior to skin testing and kept at -70 degrees C until analysis for antibody assay by the indirect fluorescent antibody (IFA) method. RESULTS: Forty three patients were IFA antibody positive; 41 of them reacted to the skin test. One of the 20 IFA negative patients reacted to the skin test. Sixteen patients had two serological tests performed, one month apart. Four out of these 16 patients tested negative with the skin test. All four had negative serology on both samples. Six of the 12 IFA positive patients showed a boost in the antibody titre one month after application of the skin test. The specificity and sensitivity of the skin test compared to the IFA assay were both 95%, and the positive and negative predictive values were 97% and 90% respectively. CONCLUSIONS: Results suggest that a varicella skin test prepared using this simple and relatively cheap method is a safe, sensitive, and specific tool by which to assess immunity to varicella.
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Varicela/inmunología , Pruebas Intradérmicas/métodos , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Vacuna contra la Varicela/inmunología , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Vacunas Atenuadas/inmunologíaRESUMEN
Shwachman-Diamond syndrome (SDS) is an inherited multisystem disorder characterized by exocrine pancreatic dysfunction and varying degrees of cytopenia. In addition, various immunological abnormalities have been noted. To clarify the issue of immunological competence or incompetence in SDS, we prospectively studied immune function in 11 patients with SDS. Seven suffered from recurrent bacterial infections and six from recurrent viral infections. Varying degrees of impairment were readily identified. All patients had neutropenia; total lymphocyte counts, however, were normal in all except one patient. Nine patients had B-cell defects comprising one or more of the following abnormalities: low IgG or IgG subclasses, low percentage of circulating B lymphocytes, decreased in vitro B-lymphocyte proliferation and a lack of specific antibody production. Seven out of nine patients studied had at least one T-cell abnormality comprising a low percentage of total circulating T lymphocytes or CD3+/CD4+ cell subpopulations or decreased in vitro T-lymphocyte proliferation. Five out of six patients studied had decreased percentages of circulating natural killer cells. Moreover, neutrophil chemotaxis was significantly low in all the patients studied. These data point to a major immunodeficiency component in SDS that places patients at heightened risk of infections, even if neutrophil numbers are protective. This finding broadens the definition of the syndrome substantially: it suggests that the SDS marrow defect occurs at the level of an early haematological-lymphocytic stem cell or that a combined marrow and thymic stromal defect accounts for the aberrant function of haematopoietic and lymphopoietic lineages.
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Médula Ósea/inmunología , Neutropenia/inmunología , Enfermedades Pancreáticas/inmunología , Adolescente , Linfocitos B/inmunología , Infecciones Bacterianas/inmunología , División Celular , Quimiotaxis de Leucocito , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina G/inmunología , Lactante , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Masculino , Neutrófilos/inmunología , Estudios Prospectivos , Síndrome , Linfocitos T/inmunología , Virosis/inmunologíaRESUMEN
Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive disease, which presents clinically as severe combined immunodeficiency (SCID). We report here two novel mutations in the PNP gene that result in SCID phenotype, in a single patient. The maternal-derived allele carries a C to T transition in exon 2 resulting in a premature stop codon at amino acid 57. The paternal-derived mutation is a G to A transition at position +1 in intron 3, causing a complete skipping of exon 3 and a reading frameshift at the exon 2-exon 4 junction. The predicted polypeptide encoded by the aberrantly spliced mRNA terminates prematurely after only 89 amino acids. Both mutations predict severely truncated proteins resulting in a complete deficiency of PNP enzymatic activity, yet the development of profound immunodeficiency in this patient is greatly delayed.
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Mutación , Purina-Nucleósido Fosforilasa/genética , Inmunodeficiencia Combinada Grave/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Preescolar , ADN Complementario , Exones , Femenino , Humanos , Intrones , Masculino , Datos de Secuencia Molecular , Mutación Puntual , Purina-Nucleósido Fosforilasa/deficiencia , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Inmunodeficiencia Combinada Grave/genética , Inmunodeficiencia Combinada Grave/inmunologíaRESUMEN
Most cases of chronic urticaria (CU) are considered idiopathic. It has recently been accepted that autoimmunity plays a critical role in the pathogenesis of CU in some of these patients. Although urticaria is common in the pediatric population, the knowledge regarding CU-associated autoimmunity is very limited. We describe the association of CU with a wide spectrum of clinical and laboratory autoimmune disorders in 2 children and emphasize the concept that CU is another manifestation of the "autoimmune kaleidoscope."
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Enfermedades Autoinmunes/diagnóstico , Urticaria/diagnóstico , Adolescente , Enfermedades Autoinmunes/inmunología , Niño , Enfermedad Crónica , Femenino , Humanos , Masculino , Urticaria/inmunologíaRESUMEN
We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. PNP knockout mice exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, and decreased numbers of maturing thymocytes and peripheral T cells. T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro. We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria. The end result is increased sensitivity of T cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.
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Nucleótidos de Desoxiguanina/metabolismo , Mitocondrias/metabolismo , Purina-Nucleósido Fosforilasa/deficiencia , Purina-Nucleósido Fosforilasa/genética , Inmunodeficiencia Combinada Grave/etiología , Linfocitos T/metabolismo , Animales , Apoptosis , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular , Citotoxicidad Inmunológica , Ratones , Ratones Noqueados , Subgrupos de Linfocitos T/metabolismo , Timo/citologíaRESUMEN
Bone marrow transplantation (BMT) from siblings is the treatment of choice for severe combined immunodeficiency (SCID). The objective of this study was to evaluate the efficiency of BMT from matched unrelated donors (MUD) in congenital immunodeficiencies when a sibling donor is unavailable. Sixteen consecutive patients with SCID (n = 9) and CID (n= 7), were referred for an unrelated donor search. Acceptable donors were found for all patients. Fifteen patients received busulfan and cyclophosphamide pretransplant conditioning. One patient had an early loss of graft and was reconditioned using cyclophosphamide and total body irradiation. The graft-versus-host disease (GVHD) prophylaxis used was methylprednisolone, cyclosporin A with or without methotrexate. Neutrophil engraftment was rapid and was achieved in all patients within a mean of 15.4 days. Only 13 episodes of fever were recorded shortly after BMT. GVHD of grade II or more was apparent in 2/9 (22%) of SCID patients and in 4/7 (57%) of CID patients. Overall survival was 75% with a mean follow-up of 47.4 months (range 18-101). Six out of nine SCID patients (67%) and 6/7 (86%) of CID patients are alive and well. Eleven patients had normal humoral immunity, and cell-mediated immunity as measured by flow cytometry and mitogenic responses, was intact in all patients. Intradermal candida skin test was positive in 9/10 patients tested. We conclude that BMT from MUD results in rapid engraftment and is therefore associated with a low rate of infection contributing to the improved survival rate. The protocol used is especially favorable for patients with combined immunodeficiency.