RESUMEN
BACKGROUND: Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is approved by EMA for relapsing-remitting multiple sclerosis (RRMS). OBJECTIVES: To assess the effectiveness and safety of fingolimod in patients with RRMS in real-world clinical practice in Portugal. METHODS: Retrospective, multicentre, non-interventional study, reporting 3 years follow-up of data collected from October 2015 to July 2016. Sociodemographic data and previous treatments at baseline and data regarding disease evolution, including number of relapses, annualised relapse rates (ARR) and Expanded Disability Status Scale (EDSS), were collected. RESULTS: Two-hundred and seventy-five participants were enrolled in the REALMS study. Results showed that the main reason to switch to fingolimod was failure of previous treatment (56.7%) and only 3.6% were naïve patients. In the total population, there was a significant decrease in ARR of 64.6% in the first year of treatment, 79.7% in the second year and 82.3% in the third year, compared with baseline. More than 67.0% of patients had no relapses during the 3 years after switching to fingolimod. EDSS remained stable throughout the study. CONCLUSIONS: Therapy with fingolimod showed a sustained effectiveness and safety over the 3 years, particularly on patients switched from first-line drugs (BRACE). No new safety issues were reported.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Clorhidrato de Fingolimod/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Portugal/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We sought to determine whether high-dose folinic acid improves verbal communication in children with non-syndromic autism spectrum disorder (ASD) and language impairment in a double-blind placebo control setting. Forty-eight children (mean age 7 years 4 months; 82% male) with ASD and language impairment were randomized to receive 12 weeks of high-dose folinic acid (2 mg kg-1 per day, maximum 50 mg per day; n=23) or placebo (n=25). Children were subtyped by glutathione and folate receptor-α autoantibody (FRAA) status. Improvement in verbal communication, as measured by a ability-appropriate standardized instrument, was significantly greater in participants receiving folinic acid as compared with those receiving placebo, resulting in an effect of 5.7 (1.0,10.4) standardized points with a medium-to-large effect size (Cohen's d=0.70). FRAA status was predictive of response to treatment. For FRAA-positive participants, improvement in verbal communication was significantly greater in those receiving folinic acid as compared with those receiving placebo, resulting in an effect of 7.3 (1.4,13.2) standardized points with a large effect size (Cohen's d=0.91), indicating that folinic acid treatment may be more efficacious in children with ASD who are FRAA positive. Improvements in subscales of the Vineland Adaptive Behavior Scale, the Aberrant Behavior Checklist, the Autism Symptom Questionnaire and the Behavioral Assessment System for Children were significantly greater in the folinic acid group as compared with the placebo group. There was no significant difference in adverse effects between treatment groups. Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs.
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Leucovorina/farmacología , Conducta Verbal/efectos de los fármacos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno Autístico/tratamiento farmacológico , Niño , Trastornos Generalizados del Desarrollo Infantil/tratamiento farmacológico , Preescolar , Método Doble Ciego , Femenino , Receptor 1 de Folato/metabolismo , Humanos , Trastornos del Desarrollo del Lenguaje/tratamiento farmacológico , Trastornos del Lenguaje/tratamiento farmacológico , Leucovorina/metabolismo , Masculino , Efecto Placebo , Receptores de Péptidos/metabolismo , Resultado del TratamientoRESUMEN
INTRODUCTION: Cerebral folate deficiency (CFD) syndromes are defined as neuro-psychiatric conditions with low CSF folate and attributed to different causes such as autoantibodies against the folate receptor-alpha (FR) protein that can block folate transport across the choroid plexus, FOLR1 gene mutations or mitochondrial disorders. High-dose folinic acid treatment restores many neurologic deficits. STUDY AIMS AND METHODS: Among 36 patients from 33 families the infantile-onset CFD syndrome was diagnosed based on typical clinical features and low CSF folate. All parents were healthy. Three families had 2 affected siblings, while parents from 4 families were first cousins. We analysed serum FR autoantibodies and the FOLR1 and FOLR2 genes. Among three consanguineous families homozygosity mapping attempted to identify a monogenetic cause. Whole exome sequencing (WES) was performed in the fourth consanguineous family, where two siblings also suffered from polyneuropathy as an atypical finding. RESULTS: Boys (72%) outnumbered girls (28%). Most patients (89%) had serum FR autoantibodies fluctuating over 5-6â¯weeks. Two children had a genetic FOLR1 variant without pathological significance. Homozygosity mapping failed to detect a single autosomal recessive gene. WES revealed an autosomal recessive polynucleotide kinase 3´phosphatase (PNKP) gene abnormality in the siblings with polyneuropathy. DISCUSSION: Infantile-onset CFD was characterized by serum FR autoantibodies as its predominant pathology whereas pathogenic FOLR1 gene mutations were absent. Homozygosity mapping excluded autosomal recessive inheritance of any single responsible gene. WES in one consanguineous family identified a PNKP gene abnormality that explained the polyneuropathy and also its contribution to the infantile CFD syndrome because the PNKP gene plays a dual role in both neurodevelopment and immune-regulatory function. Further research for candidate genes predisposing to FRα-autoimmunity is suggested to include X-chromosomal and non-coding DNA regions.
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Autoanticuerpos/sangre , Encefalopatías Metabólicas Innatas/genética , Receptor 1 de Folato/inmunología , Deficiencia de Ácido Fólico/genética , Adolescente , Encefalopatías Metabólicas Innatas/líquido cefalorraquídeo , Encefalopatías Metabólicas Innatas/diagnóstico , Niño , Preescolar , Consanguinidad , Enzimas Reparadoras del ADN/genética , Diagnóstico Diferencial , Familia , Femenino , Receptor 1 de Folato/genética , Receptor 2 de Folato/genética , Ácido Fólico/líquido cefalorraquídeo , Deficiencia de Ácido Fólico/líquido cefalorraquídeo , Deficiencia de Ácido Fólico/diagnóstico , Humanos , Lactante , Masculino , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Polineuropatías/etiología , Secuenciación del Exoma , Adulto JovenRESUMEN
Folate receptor alpha (FRα) autoantibodies have been associated with fetal abnormalities and cerebral folate deficiency-related developmental disorders. Over 70% of the children with autism spectrum disorders (ASD) are positive for these autoantibodies and high-dose folinic acid is beneficial in treating these children. Here we show that antibodies (Abs) to the rat FRα administered during gestation produce communication, learning and cognitive deficits in a rat model that can be prevented by folinic acid and dexamethasone. FRα Ab can trigger inflammation as well as block folate transport to the fetus and to the developing brain to produce the functional deficits. In humans, exposure to FRα autoantibodies during fetal development and infancy could contribute to brain dysfunction such as that seen in ASD and other developmental disorders. Identifying women positive for the autoantibody and treating them with high-dose folinic acid along with other interventions to lower the autoantibody titer are effective strategies that may be considered to reduce the risk of having a child with developmental deficits.
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Trastorno Autístico/tratamiento farmacológico , Trastorno Autístico/inmunología , Receptor 1 de Folato/deficiencia , Animales , Anticuerpos , Trastorno Autístico/metabolismo , Autoanticuerpos/inmunología , Niño , Trastornos del Conocimiento/tratamiento farmacológico , Dexametasona/uso terapéutico , Femenino , Receptor 1 de Folato/antagonistas & inhibidores , Receptor 1 de Folato/inmunología , Receptor 1 de Folato/metabolismo , Ácido Fólico , Humanos , Leucovorina/uso terapéutico , Masculino , Embarazo , Ratas , Ratas Long-EvansRESUMEN
OBJECTIVES: Post-appendectomy intra-abdominal abscesses are estimated to complicate up to 4.2% of acute non-perforated appendicitis and between 6.7% and 28% acute perforated appendicitis. This study was performed with the aim to review and characterize post-appendectomy intra-abdominal abscesses in our Pediatric Surgery department; to calculate their incidence and to evaluate the efficacy of the treatment modality. MATERIAL AND METHODS: A retrospective analysis of all patients, under 18 years and with the diagnosis of intra-abdominal abscess post-appendectomy, between January 2010 and December 2015 was performed, taking in account initial surgical approach, type of acute appendicitis, length of hospital stay and the treatment applied. Data were collected by reviewing clinical files. RESULTS: In a total of 1,340 appendectomies performed, there were 24 intra-abdominal abscesses identified (1.79%). Eight were feminine and sixteen masculine, and mean age was 11.9 years. In 52% of cases the diagnosis was made in the initial admission. Twelve have been submitted to laparoscopic appendectomy and the other 12 to open appendectomy. Of the 24 patients, only 4 needed a surgical re-intervention, which leaves medical treatment an 83.3% success rate. CONCLUSIONS: TThe incidence of intra-abdominal abscesses post-appendectomy, in the studied population, is what was expected and inferior to what's described in the literature. In our sample, conservative management for intra-abdominal abscesses post-appendectomy was successful in most of the cases, only 4 needing further surgical intervention.
OBJETIVOS: Se estima que la frecuencia en la que aparecen los abscesos intraabdominales postapendicectomía es de un 4,2% en las apendicitis agudas no perforadas y entre un 6,7 y 28% en las apendicitis agudas perforadas. Este estudio fue realizado con el objetivo de revisar los casos de abscesos intraabdominales en el postoperatorio de apendicectomía por apendicitis aguda en nuestro Servicio de Cirugía Pediátrica, calcular su incidencia y evaluar la eficacia del tratamiento implementado. MATERIAL Y METODO: Análisis retrospectivo de los pacientes, menores de 18 años y con diagnóstico de absceso intraabdominal postapendicectomía, entre enero de 2010 y diciembre de 2015, teniendo en cuenta el abordaje quirúrgico inicial, el tipo de apendicitis aguda, la duración del internamiento y el tipo de tratamiento efectuado. RESULTADOS: En un total de 1.340 apendicectomías realizadas se identificaron 24 abscesos intraabdominales (1,79%): ocho del sexo femenino y dieciséis del sexo masculino, con una media de edad de 11,9 años. En el 52% de los casos el diagnóstico fue realizado durante el ingreso inicial. Doce pacientes fueron sometidos a apendicectomía laparoscópica y 12 por laparotomía. De los 24 pacientes solamente 4 necesitaron de nuevo una intervención quirúrgica. Por lo tanto, el porcentaje de éxito del tratamiento médico fue de un 83,3%. CONCLUSIONES: La incidencia de abscesos intraabdominales postapendicectomía en la población estudiada está dentro de lo esperado e incluso es inferior a los valores mencionados en la literatura. En nuestra muestra con el tratamiento médico de los abscesos intraabdominales tuvimos muy buenos resultados en la mayoría de los casos, necesitando solo en 4 recurrir al tratamiento quirúrgico.
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Absceso Abdominal/epidemiología , Apendicectomía/métodos , Apendicitis/cirugía , Complicaciones Posoperatorias/epidemiología , Absceso Abdominal/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Laparoscopía/métodos , Tiempo de Internación , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: A standardised nutrition risk screening (NRS) programme with ongoing education is recommended for the successful implementation of NRS. This project aimed to develop and implement a standardised NRS and education process across the adult bed-based services of a large metropolitan health service and to achieve a 75% NRS compliance at 12 months post-implementation. METHODS: A working party of Monash Health (MH) dietitians and a nutrition technician revised an existing NRS medical record form consisting of the Malnutrition Universal Screening Tool and nutrition management guidelines. Nursing staff across six MH hospital sites were educated in the use of this revised form and there was a formalised implementation process. Support from Executive Management, nurse educators and the Nutrition Risk Committee ensured the incorporation of NRS into nursing practice. Compliance audits were conducted pre- and post-implementation. RESULTS: At 12 months post-implementation, organisation-wide NRS compliance reached 34.3%. For those wards that had pre-implementation NRS performed by nursing staff, compliance increased from 7.1% to 37.9% at 12 months (P < 0.001). The improved NRS form is now incorporated into standard nursing practice and NRS is embedded in the organisation's 'Point of Care Audit', which is reported 6-monthly to the Nutrition Risk Committee and site Quality and Safety Committees. CONCLUSIONS: NRS compliance improved at MH with strong governance support and formalised implementation; however, the overall compliance achieved appears to have been affected by the complexity and diversity of multiple healthcare sites. Ongoing education, regular auditing and establishment of NRS routines and ward practices is recommended to further improve compliance.
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Implementación de Plan de Salud , Desnutrición/diagnóstico , Tamizaje Masivo/normas , Evaluación Nutricional , Medición de Riesgo/normas , Adulto , Adhesión a Directriz/estadística & datos numéricos , Hospitales/normas , Humanos , VictoriaRESUMEN
INTRODUCTION: Sialorrhea is a medical problem and can become a social issue, common in children with neurological disabilities. The bilateral submandibulectomy is one of the available treatment options for managing this pathology. AIM OF THE STUDY: The aim of this study is to evaluate the effectiveness of bilateral submandibulectomy in the management of sialorrhea in children with neurological disabilities through the parents' satisfaction grade. PATIENTS AND METHODS: We retrospectively analyzed 91 bilateral submandibulectomies for a period of time of 10 years (2004-2015). Data were taken from surgical records and patients files and were informatically processed. The severity grade before and after surgery was evaluated in line with the modified Teacher scale. Parental satisfaction was evaluated by applying a scale graded into five classes, according to the degree of sialorrhea severity in postoperative period. RESULTS: During the reporting period, 91 children underwent bilateral submandibulectomy in our center. Of these, 7 cases were excluded for lack of data. The average age of the children was 8,9 [± 3,5] years; 58,3% were male. The degree of preoperative sialorrhea severity was, in 52,4% of cases, level 4 (severe drooling), and in 28,6%, level 5 (very severe). The grade of parental satisfaction in postoperative period was ranked, in 73,8% of cases, between 81-100%. CONCLUSIONS: For children with drooling, a bilateral submandibulectomy emerges as an effective and efficient treatment, leaving parents with an extremely high satisfaction grade.
INTRODUCCION: La sialorrea es un problema médico y social, común en los niños con enfermedad neurológica. La submandibulectomía surge como una opción terapéutica posible y eficaz para esta patología. OBJETIVO: Evaluar la eficacia de la submandibulectomía bilateral, a través del grado de satisfacción de los padres de niños con sialorrea, sometidos a este procedimiento. MATERIAL Y METODOS: Análisis retrospectivo de 91 casos de niños sometidos a submandibulectomía bilateral durante 10 años (2004 a 2015). Los datos fueron obtenidos de los registros clínicos de cada paciente y tratados informáticamente. El grado de severidad en el pre y postoperatorio fue evaluado según la escala de Teacher modificada. La satisfacción de los padres fue evaluada a través de la aplicación de una escala que se divide en 5 clases, conforme el grado de severidad de sialorrea en el postoperatorio. RESULTADOS: Durante el periodo analizado, fueron sometidos a submandibulectomía bilateral 91 niños. De estos, fueron excluidos 7 casos por ausencia de datos. La edad media de los niños fue de 8,9 [± 3,5] años, siendo 58,3% del sexo masculino. El grado de severidad de sialorrea preoperatoria fue, en 52,4% de los casos, de nivel 4 (sialorrea grave) y, en 28,6%, de nivel 5 (muy grave). El grado de satisfacción de los padres fue alto o muy alto en el 94% de los casos. CONCLUSION: Para los niños con sialorrhea, la submandibulectomía surge como un tratamiento eficaz, que deja a los padres muy satisfechos y permite una mejor integración de los niños en la sociedad.
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Padres/psicología , Sialorrea/cirugía , Glándula Submandibular/cirugía , Niño , Femenino , Humanos , Masculino , Satisfacción Personal , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
This study investigates the effects of different doses of serotonin, its precursor 5-hydroxytry-ptophan (5HTP), and m-hydroxybenzylhydrazine inhibitor (NSD1015), administered via intraperitoneal for 5 consecutive days, on behavior and average body weight of broilers. We also measured the humoral immune response and quantification of Salmonella Enteritidis in broilers chickens that received the drugs evaluated and a Lactobacillus pool. The study was divided into 3 experiments: Experiment 1--administration of pharmaceuticals with choice of dosage; Experiment 2--administration of pharmaceuticals and a Lactobacillus pool in birds that were not challenged with S. Enteritidis, and Experiment 3--administration of pharmaceuticals and a Lactobacillus pool in birds challenged with S. Enteritidis. The ELISA was used to scan dosages of intestinal IgA and serum IgY. We used colony-forming units to quantify S. Enteritidis. The concentrations of IgA and IgY did not show significant differences (P>0.05) in Experiment 2. In Experiment 3, NSD1015 associated with Lactobacillus determined higher IgA concentrations, promoting greater stimulus to the immune system than 5HTP. Regarding quantification of S. Enteritidis in the cecal content of birds, 5HTP associated to Lactobacillus determined the smallest number of bacteria, showing possible interaction of 5-hydroxytryptophan and Lactobacillus spp. with the immune system of broiler chickens.
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Pollos , Inmunidad Humoral/efectos de los fármacos , Lactobacillus/química , Enfermedades de las Aves de Corral/inmunología , Probióticos/farmacología , Salmonelosis Animal/inmunología , Antagonistas de la Serotonina/farmacología , 5-Hidroxitriptófano/farmacología , Animales , Ciego/microbiología , Recuento de Colonia Microbiana/veterinaria , Dieta/veterinaria , Suplementos Dietéticos/análisis , Hidrazinas/farmacología , Masculino , Enfermedades de las Aves de Corral/microbiología , Probióticos/administración & dosificación , Distribución Aleatoria , Salmonelosis Animal/microbiología , Salmonella enteritidis/fisiologíaRESUMEN
BACKGROUND: Auto-antibodies against folate receptor alpha (FRα) at the choroid plexus that block N(5)-methyltetrahydrofolate (MTHF) transfer to the brain were identified in catatonic schizophrenia. Acoustic hallucinations disappeared following folinic acid treatment. Folate transport to the CNS prevents homocysteine accumulation and delivers one-carbon units for methyl-transfer reactions and synthesis of purines. The guanosine derivative tetrahydrobiopterin acts as common co-factor for the enzymes producing dopamine, serotonin and nitric oxide. METHODS: Our study selected patients with schizophrenia unresponsive to conventional treatment. Serum from these patients with normal plasma homocysteine, folate and vitamin B12 was tested for FR autoantibodies of the blocking type on serial samples each week. Spinal fluid was analyzed for MTHF and the metabolites of pterins, dopamine and serotonin. The clinical response to folinic acid treatment was evaluated. RESULTS: Fifteen of 18 patients (83.3%) had positive serum FR auto-antibodies compared to only 1 in 30 controls (3.3%) (χ(2)=21.6; p<0.0001). FRα antibody titers in patients fluctuated over time varying between negative and high titers, modulating folate flux to the CNS, which explained low CSF folate values in 6 and normal values in 7 patients. The mean±SD for CSF MTHF was diminished compared to previously established controls (t-test: 3.90; p=0.0002). A positive linear correlation existed between CSF MTHF and biopterin levels. CSF dopamine and serotonin metabolites were low or in the lower normal range. Administration of folinic acid (0.3-1mg/kg/day) to 7 participating patients during at least six months resulted in clinical improvement. CONCLUSION: Assessment of FR auto-antibodies in serum is recommended for schizophrenic patients. Clinical negative or positive symptoms are speculated to be influenced by the level and evolution of FRα antibody titers which determine folate flux to the brain with up- or down-regulation of brain folate intermediates linked to metabolic processes affecting homocysteine levels, synthesis of tetrahydrobiopterin and neurotransmitters. Folinic acid intervention appears to stabilize the disease process.
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Autoanticuerpos/sangre , Receptor 1 de Folato/inmunología , Leucovorina/administración & dosificación , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/inmunología , Adolescente , Adulto , Biopterinas/líquido cefalorraquídeo , Niño , Femenino , Ácido Fólico/análogos & derivados , Ácido Fólico/sangre , Ácido Fólico/líquido cefalorraquídeo , Homocisteína , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood-brain barrier. Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated. In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case. Children with FRAs were treated with oral leucovorin calcium (2 mg kg(-1) per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment. Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.
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Autoanticuerpos/sangre , Trastornos Generalizados del Desarrollo Infantil/tratamiento farmacológico , Trastornos Generalizados del Desarrollo Infantil/inmunología , Receptor 1 de Folato/inmunología , Leucovorina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Adolescente , Niño , Trastornos Generalizados del Desarrollo Infantil/sangre , Trastornos Generalizados del Desarrollo Infantil/líquido cefalorraquídeo , Preescolar , Femenino , Humanos , Leucovorina/efectos adversos , Masculino , Tetrahidrofolatos/líquido cefalorraquídeo , Complejo Vitamínico B/efectos adversosRESUMEN
This study investigated the immune response of broiler chickens with oral treatment of a Lactobacillus spp. pool (PL) associated with microencapsulated recombinant proteins flagellin (FliC) and the subunit B of cholera toxin (CTB). Immune responses were evaluated by measuring IgA from intestinal fluid, serum IgY, and immunostaining of CD8(+) T lymphocytes present in the cecum. The evaluations were performed on d 0, 7, 14, 21, and 28 posttreatment. A significant increase (P < 0.05) was observed in IgA levels in all immunized groups, especially 3 wk after immunization. Treatments 2 (recombinant CTB) and 3 (recombinant FliC+CTB) showed the highest concentrations. Similarly, serum concentrations IgY (µg/mL) increased along the experiment, and the means for treatments 2 and 3 showed significant differences (P < 0.05) compared with controls, reaching concentrations of 533 and 540 µg/mL, respectively. The number of CD8(+) T lymphocytes in all treatments greatly differed (P < 0.05) compared with the negative control at 21 d posttreatment. However, only treatment 2 (recombinant CTB), 4 (PL), and 5 (recombinant FliC+ recombinant CTB + PL) remained significantly (P < 0.05) different from the control at 28 d posttreatment. Thus, it is concluded that the microencapsulated recombinant proteins administered orally to broiler chickens are capable of stimulating humoral and cellular immune response, and the combinations of these antigens with Lactobacillus spp. can influence the population of CD8(+) T cells residing in the cecum.
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Pollos , Toxina del Cólera/inmunología , Cólera/veterinaria , Flagelina/inmunología , Inmunidad Mucosa/inmunología , Lactobacillus , Adyuvantes Inmunológicos , Administración Oral , Animales , Linfocitos T CD8-positivos , Cólera/prevención & control , Inmunoglobulinas/sangre , Proteínas Recombinantes/inmunologíaRESUMEN
Background: The oral cavity is a unique environment where wound healing needs to occur in the presence of heavily contaminated oral fluid often leading to infections at the suture site. Topical antimicrobial agents have proven to be effective in controlling intraoral infections. One such antimicrobial combination is Metronidazole-Chlorhexidine which has commonly been used to treat oral ulcers and gingival inflammation; however, there are no studies of its use in the healing of oral incisions. Methodology: This split-mouth study comprised of 15 participants who received 30 intraoral incisions. Incisions were placed either simultaneously (Group 1) or at spaced intervals (Group 2) for various minor and major surgical procedures. Metronidazole -Chlorhexidine gel was applied to the study sites while the control sites were allowed to heal naturally. Pain, inflammation, and healing were assessed using visual analogue scale and healing index by Landry et al. Results: The study sites showed better wound healing and decreased postoperative inflammation. There was a statistically significant decrease in post-operative pain in the study site in Group 1 but not in Group 2. Conclusion: Metronidazole-Chlorhexidine combination gel is a cost-effective, readily available, and safe medicament to improve healing of intraoral incisions and reduce post-operative inflammation and pain.
RESUMEN
Adenoid squamous cell carcinoma (ASCC) is an uncommon but well recognized variant of squamous cell carcinoma. It has been reported to originate in the sun exposed skin of the head and neck region. Although rare, there are cases in records which have reported within the oral cavity and nasopharynx. Histologically the lesion shows areas of conventional squamous cell carcinoma along with atypical epithelial cells forming an adenoid pattern. There are insufficient reported cases to establish likely behaviour. Here we report two additional cases of adenoid squamous cell carcinoma, one developing in the floor of mouth and another in the maxillary sinus both were reported in March 2010 in Mangalore, India.
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Tonsila Faríngea/patología , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias del Seno Maxilar/diagnóstico , Suelo de la Boca/patología , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Neoplasias de Cabeza y Cuello/patología , Humanos , India , Masculino , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
Purpose: The conventional alveoloplasty approach which uses manual equipment results in more resorption of the underlying alveolar ridge that makes denture prosthesis unstable. The goal of this study was to compare results of piezosurgery alveoloplasty to those of conventional alveoloplasty. Materials and Methods: This was an in-vivo comparative study consisting of ten edentulous individuals who needed alveoloplasty due to bilateral bony projection. On one side, a conventional alveoloplasty was performed with a bone rongeur and bone file, whereas the contralateral side was treated with a piezosurgery unit. The clinical parameters were analyzed using SPSS version 21 software including operating time, postoperative pain evaluation on day 3 and a healing on day 7. Results: There was a statistically significant difference between the two groups in terms of outcome variables such as operating time, pain and healing. The Conventional group has a lower mean of operating time, a higher mean rank of VAS and a lower mean rank of healing index compared to the piezosurgery group. Conclusion: Piezosurgery alveoloplasty not only lowers postoperative patient discomfort but also preserves alveolar bone integrity by not disrupting soft and hard tissue architecture thus allowing faster tissue healing and easier prosthesis replacement in the future.
RESUMEN
OBJECTIVE: Women who have low cobalamin (vitamin B(12)) levels are at increased risk for having children with neural tube defects (NTDs). The transcobalamin II receptor (TCblR) mediates uptake of cobalamin into cells. Inherited variants in the TCblR gene as NTD risk factors were evaluated. METHODS: Case-control and family-based tests of association were used to screen common variation in TCblR as genetic risk factors for NTDs in a large Irish group. A confirmatory group of NTD triads was used to test positive findings. RESULTS: 2 tightly linked variants associated with NTDs in a recessive model were found: TCblR rs2336573 (G220R; p(corr)=0.0080, corrected for multiple hypothesis testing) and TCblR rs9426 (p(corr)=0.0279). These variants were also associated with NTDs in a family-based test before multiple test correction (log-linear analysis of a recessive model: rs2336573 (G220R; RR=6.59, p=0.0037) and rs9426 (RR=6.71, p=0.0035)). A copy number variant distal to TCblR and two previously unreported exonic insertion-deletion polymorphisms were described. CONCLUSIONS: TCblR rs2336573 (G220R) and TCblR rs9426 represent a significant risk factor in NTD cases in the Irish population. The homozygous risk genotype was not detected in nearly 1000 controls, indicating that this NTD risk factor may be of low frequency and high penetrance. 9 other variants are in perfect linkage disequilibrium with the associated single nucleotide polymorphisms. Additional work is required to identify the disease-causing variant. Our data suggest that variation in TCblR plays a role in NTD risk and that these variants may modulate cobalamin metabolism.
Asunto(s)
Predisposición Genética a la Enfermedad , Defectos del Tubo Neural/genética , Polimorfismo Genético , Receptores de Superficie Celular/genética , Alelos , Estudios de Casos y Controles , Estudios de Cohortes , Familia , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Irlanda , Masculino , Receptores de Superficie Celular/metabolismo , Factores de Riesgo , Transcobalaminas/metabolismoRESUMEN
We describe a 3.5-year-old female with Alpers disease with a POLG genotype of p.A467T/p.G848S and with a lethal outcome. Laboratory investigation revealed elevated CSF neopterin, IL-6, IL-8, IFN-gamma, reduced CSF 5-methyltetrahydrofolate (5MTHF), and increased serum as well as CSF folate receptor blocking autoantibodies. Treatment with oral Leucovorine (5-formyl-tetrahydrofolate) was initiated at 0.25mg/kg bid, and later increased to 4mg/kg bid. Under treatment CSF levels of 5MTHF, seizure frequency and communicative abilities improved. Over a time span of 17months, CSF levels of IL-6 and IFN-gamma decreased, levels of folate receptor blocking autoantibodies continued to raise, whereas CSF IL-8 remained elevated 1500-fold above normal. The child died without apparent stress at the age of 5.5years. Alpers disease, a neurodegenerative disease usually presents in the first years of life as a progressive encephalopathy with multifocal myoclonic seizures, developmental regression, cortical blindness and early death. The underlying genetic defect has been attributed to mutations of the catalytic subunit of the mitochondrial DNA polymerase-gamma leading to an organ-specific mitochondrial DNA depletion syndrome with reduced activity of respiratory chain enzyme complexes in the brain and the liver. A curative therapy is not available. This case report of Alpers disease provides new insights into the pathophysiology of Alpers disease, where mitochondrial dysfunction in conjunction with inflammatory cytokines and blocking folate receptor autoantibodies may lead to a secondary cerebral folate deficiency syndrome. The treatment of the latter provides relief to the patient without stopping the underlying disease.
Asunto(s)
Esclerosis Cerebral Difusa de Schilder/líquido cefalorraquídeo , Ácido Fólico/líquido cefalorraquídeo , Mediadores de Inflamación/líquido cefalorraquídeo , Sustitución de Aminoácidos , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Encéfalo/metabolismo , Encéfalo/patología , Proteínas Portadoras/inmunología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Preescolar , ADN Polimerasa gamma , ADN Polimerasa Dirigida por ADN/genética , Esclerosis Cerebral Difusa de Schilder/genética , Esclerosis Cerebral Difusa de Schilder/metabolismo , Resultado Fatal , Femenino , Receptores de Folato Anclados a GPI , Ácido Fólico/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Interferón gamma/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Neopterin/líquido cefalorraquídeo , Receptores de Superficie Celular/inmunologíaRESUMEN
AIM: Occlusion and reperfusion of splanchnic arteries cause local and systemic changes due to the release of cytotoxic substances and the interaction between neutrophils and endothelial cells. This study evaluated the role of pentoxifylline (PTX) and n-acetylcysteine (NAC) in the reduction of ischemia, reperfusion shock and associated intestinal injury. METHODS: Sixty rats were divided into 6 groups of 10 animals. Rats in three groups underwent mesenteric ischemia for 30 minutes followed by 120 minutes of reperfusion, and were treated with saline (SAL-5 mL/kg/h), pentoxifylline (PTX-50 mg/kg) or n-acetylcysteine (NAC-430 mg/kg/h). The other 3 groups underwent sham ischemia and reperfusion (I/R) and received the same treatments. Hemodynamic, biochemical and histological parameters were evaluated. RESULTS: No significant hemodynamic or intestinal histological changes were seen in any sham group. No histological changes were found in the lung or liver of animals in the different groups. There was a progressive decrease in mean arterial blood pressure, from mean of 111.53 mmHg (30 minutes of ischemia) to 44.30+/-19.91 mmHg in SAL-I/R, 34.52+/-17.22 mmHg in PTX-I/R and 33.81+/-8.39 mmHg in NAC-I/R (P<0.05). In all I/R groups, there was a progressive decrease in: aortic blood flow, from median baseline of 19.00 mL/min to 2.50+/-5.25 mL/min in SAL-I/R; 2.95+/-6.40 mL/min in PTX-I/R and 3.35+/-3.40 mL/min in NAC-I/R (P<0.05); in the heart rate, from mean baseline of 311.74 bpm to 233.33+/-83.88 bpm in SAL-I/R, 243.20+/-73.25 bpm in PTX-I/R and 244.92+/-76.05 bpm in NAC-I/R (P<0.05); and esophageal temperature, from mean baseline of 33.68 degrees C to 30.53+/-2.05 degrees C in SAL-I/R, 30.69+/-2.21 degrees C in PTX-I/R and 31.43+/-1.03 degrees C in NAC-I/R (P<0.05). In the other hand, there was an attenuation of mucosal damage in the small intestine of the animals receiving PTX, and only in the ileum of the animals receiving NAC. No changes were found in ileum or plasma malondialdehyde levels in any group. CONCLUSIONS: PTX was more efficient in reducing histological lesions than NAC, but neither treatment prevented hemodynamic changes during splanchnic organs I/R.
Asunto(s)
Acetilcisteína/farmacología , Depuradores de Radicales Libres/farmacología , Hemodinámica/efectos de los fármacos , Intestino Delgado/efectos de los fármacos , Oclusión Vascular Mesentérica/tratamiento farmacológico , Pentoxifilina/farmacología , Daño por Reperfusión/prevención & control , Circulación Esplácnica/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Intestino Delgado/irrigación sanguínea , Intestino Delgado/metabolismo , Intestino Delgado/patología , Masculino , Oclusión Vascular Mesentérica/metabolismo , Oclusión Vascular Mesentérica/patología , Oclusión Vascular Mesentérica/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Índice de Severidad de la Enfermedad , Choque/fisiopatología , Choque/prevención & control , Factores de TiempoRESUMEN
Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.