RESUMEN
Skeletal fractures (SFs) are very common in pediatrics. In some cases, they are secondary to child abuse. Differentiation of accidental from non-accidental fractures (NAFs) is essential as in abused children risk of further injuries leading to severe clinical problems and death is significant. Main objectives of this study were to evaluate the characteristics of SFs of children ≤3 years of age presenting to the Emergency Room (ER) of a Children's Teaching Hospital over a 12-year period and the attention paid by ER physicians to the identification of the indicators that increase suspicion of NAF and that suggest referring of the patient to the child protection agencies. This is a descriptive, retrospective study of the medical records of all the pediatric patients ≤ 36 months of age admitted to the ER of the Azienda Ospedaliera Santa Maria della Misericordia, University of Perugia, Perugia, Italy, for radiological documented SFs between January 1, 2004, and March 31, 2016. Available information was used to evaluate whether indicators of possible child abuse were documented by the ER staff and whether diagnosis of potential abuse was followed by further screening or referral to child protection agencies. During the study period, 11,136 accesses of the ER by children younger than 36 months were documented, among whom 417 presented long bone or skull fractures. Skull fractures were significantly more common among children <12 months of age (p = 0.001), whereas radius/ulna and humerus fractures were diagnosed significantly more frequently in children 12-36 months of age (p = 0.036 and p = 0.022, respectively). Recorded medical history was considered inadequate in 255 (61.2%) cases with no difference related to patient's age. Our study showed that the majority of charts in case of SFs were found to contain inadequate documentation to explain causes at the heart of the fractures and, therefore, to rule out any inflicted trauma. The development of specific referral guidelines, along with the continuous education and training of health professionals, as well as the preparation of structured medical forms, are essential measures to activate in order to improve the referral of children from the ER to child protection agencies.
RESUMEN
In the malaria vector Anopheles gambiae, tryptophan 2,3-dioxygenase (TDO) is the only enzyme able to initiate l-tryptophan degradation through the kynurenine pathway. TDO converts l-tryptophan to N-formylkynurenine by catalyzing the heme-dependent oxidative opening of the substrate indole ring. Despite the central role exerted by kynurenines in the physiology of living organisms, only a few insect TDOs have been subjected to biochemical characterization in vitro. We performed a RT-PCR-based analysis of the tissue distribution of TDO mRNA in A. gambiae that revealed a ubiquitous expression of the gene, thus further underlining the importance of the enzyme in the mosquito biology. We developed an expression/purification procedure yielding pure and active recombinant A. gambiae TDO. Spectral analyses showed that the enzyme was purified in its heme-ferric form that was subsequently used to determining the Michaelis-Menten constants of the TDO catalyzed reaction in the presence of reducing agents. The screening of a number of compounds as potential TDO modulators showed that several kynurenines and other Tryptophan-derived molecules interfere with the enzyme activity in vitro. Our study could contribute to understanding TDO regulation in vivo and to the identification of inhibitors to be used to alter Tryptophan homeostasis in the malaria vector.
Asunto(s)
Anopheles/enzimología , Triptófano Oxigenasa/aislamiento & purificación , Triptófano Oxigenasa/metabolismo , Animales , Escherichia coli/metabolismo , Cobayas , Cinética , Proteínas Recombinantes/biosíntesisRESUMEN
BACKGROUND: Visceral leishmaniasis (VL) is an anthropozoonosis caused by an intracellular parasite belonging to the genus Leishmania. In the Mediterranean region, L. donovani and L. infantum are responsible for VL and dogs are the main reservoir. Haemophagocytic lymphohistiocytosis (HLH) represents a complication of VL and consists of unrestrained activation and proliferation of lymphocytes and macrophages, leading to uncontrolled immune activation. Haemophagocytic lymphohistiocytosis may also develop during viral infection, and Epsteinâ»Barr virus (EBV) infection is one of the main HLH causes. Macrophage haemophagocytosis in the bone marrow aspirate is pathognomonic. CASE PRESENTATION: The case involves a 19-month-old male infant presenting with a high persistent fever with a fluctuating pattern, pancytopaenia, hepatosplenomegaly, and a high triglyceride level. Initial investigations showed an EBV infection. Considering the persistent signs and symptoms, bone marrow aspiration was performed and confirmed the suspicion of HLH. In addition, the presence of Leishmania infection was shown. The patient was treated with liposomal amphotericin B and had complete resolution of his symptoms. CONCLUSION: Diagnosis of VL represents a demanding challenge in endemic and non-endemic areas. Our case demonstrates that leishmaniasis should always be considered in the differential diagnosis in patients presenting with hepatosplenomegaly and cytopaenia with a persistent fever, even in cases of infectious mononucleosis. Moreover, the execution of bone marrow aspiration should not be delayed in order to diagnose and treat at an early stage the potential occurrence of VL, especially if complicated with HLH.
Asunto(s)
Antiprotozoarios/uso terapéutico , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4/aislamiento & purificación , Leishmaniasis Visceral/tratamiento farmacológico , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Coinfección/parasitología , Coinfección/virología , Infecciones por Virus de Epstein-Barr/diagnóstico , Humanos , Lactante , Italia , Leishmaniasis Visceral/diagnóstico , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , Resultado del TratamientoRESUMEN
Background: Clinically relevant neurological manifestations in children with celiac disease (CD) are unusual, especially when they are considered as signs of the onset of the disease. In this paper, a case of Guillain-Barrè syndrome (GBS) as the first manifestation of CD in a 23-month-old child is reported. Case presentation: We describe a case of CD onset with peripheral neuropathy in a 23-month-old Bulgarian boy presenting with a sudden refusal to walk and absence of deep tendon reflexes in both lower limbs. Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss. When we evaluated the child six months after the onset of the symptoms, clinical and laboratory findings showed clear signs of peripheral neuropathy associated with malnutrition. Serum deamidated gliadin and tissue transglutaminase antibodies were therefore measured. The anti-gliadin levels were more than sixteen times higher than normal and the IgA anti-transglutaminase levels were four times higher than normal. Anti-endomysium antibodies were positive, and human leukocyte antigens (HLA) II typing confirmed a genetic predisposition to CD (DQ2 positive and DQ8 negative). Given the association between the clinical evidence of the disease and the results of the celiac screening tests, a diagnosis of CD was made without biopsy confirmation of the enteropathy. The child began a restricted gluten-free diet that led to complete recovery of the peripheral neuropathy, walking, reflexes, and overall improvement after three months on the diet. Conclusion: Our case underlines the rare but possible associations between CD and peripheral neuropathy in children as an onset symptom, even in the absence of gastrointestinal manifestations, thus suggesting that CD should always be considered in the differential diagnosis of peripheral neuropathy in children. A good knowledge of the extra-intestinal manifestations of CD is essential for the rapid introduction of a gluten-free diet that could be useful for the resolution of the neurological symptoms.
Asunto(s)
Enfermedad Celíaca/diagnóstico , Dieta Sin Gluten/estadística & datos numéricos , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Bulgaria , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/terapia , Diagnóstico Diferencial , Humanos , Lactante , Masculino , Enfermedades del Sistema Nervioso Periférico/complicacionesRESUMEN
Spontaneous oxidation of 3-hydroxykynureine (3-HK), a metabolic intermediate of the tryptophan degradation pathway, elicits a remarkable oxidative stress response in animal tissues. In the yellow fever mosquito Aedes aegypti the excess of this toxic metabolic intermediate is efficiently removed by a specific 3-HK transaminase, which converts 3-HK into the more stable compound xanthurenic acid. In anopheline mosquitoes transmitting malaria, xanthurenic acid plays an important role in Plasmodium gametocyte maturation and fertility. Using the sequence information provided by the Anopheles gambiae genome and available ESTs, we adopted a PCR-based approach to isolate a 3-HK transaminase coding sequence from the main human malaria vector A. gambiae. Tissue and developmental expression analysis revealed an almost ubiquitary profile, which is in agreement with the physiological role of the enzyme in mosquito development and 3-HK detoxification. A high yield procedure for the expression and purification of a fully active recombinant version of the protein has been developed. Recombinant A. gambiae 3-HK transaminase is a dimeric pyridoxal 5'-phosphate dependent enzyme, showing an optimum pH of 7.8 and a comparable catalytic efficiency for both 3-HK and its immediate catabolic precursor kynurenine. This study may be useful for the identification of 3-HK transaminase inhibitors of potential interest as malaria transmission-blocking drugs or effective insecticides.
Asunto(s)
Anopheles/enzimología , Quinurenina/metabolismo , Transaminasas/genética , Transaminasas/metabolismo , Secuencia de Aminoácidos , Anopheles/genética , Secuencia de Bases , Catálisis , Clonación Molecular , ADN Complementario/genética , Estabilidad de Enzimas , Escherichia coli/genética , Etiquetas de Secuencia Expresada , Perfilación de la Expresión Génica , Concentración de Iones de Hidrógeno , Hidroxilación , Cinética , Quinurenina/química , Datos de Secuencia Molecular , ARN Mensajero/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Especificidad por Sustrato , Temperatura , Transaminasas/química , Transaminasas/aislamiento & purificación , Xanturenatos/metabolismoRESUMEN
In this study the authors retrospectively evaluated the feasibility and effectiveness of prolonged oral etoposide therapy in children with recurrent ependymoma. Twelve ependymoma patients with documented recurrent or persistent disease were treated between May 1998 and October 2003. All patients were treated monthly with oral VP-16 administered at a dose of 50 mg/m2/d for 21 days, with a 7-day interval between cycles, for a planned minimum number of six cycles. Response (complete plus partial) after two cycles occurred in 5 of the 12 patients (41.6%). Response plus stable disease occurred in 10 of the 12 (83.3%), with a median duration of response or stable disease of 7 months (range 4-30). The median survival was 7 months; the 2-year progression-free survival was 16.7%. These results emphasize that oral etoposide is an attractive option for childhood recurrent ependymomas in terms of administration, tolerability, and neuroradiologic response.