Utilidad de la técnica de MS-MLPA en el diagnóstico de los síndromes de Beckwith-Wiedemann y Silver-Russell / Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome

Resumen Introducción: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. Objetivo: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. Métodos: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. Resultados: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. Conclusiones: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Abstract Introduction: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. Objective: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. Methods: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. Results: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. Conclusions: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.

Síndrome de Silver-Russell: Características clínicas, de neurodesenvolvimento e comunicação: Estudo de casos clínicos / Silver-Russell syndrome: clinical, neurodevelopmental and communication characteristics: clinical case studies

RESUMO A Síndrome de Silver Russel (SSR) é uma condição geneticamente heterogênea com fenótipo clínico que inclui restrição do crescimento intrauterino e pós-natal, alterações craniofaciais, assimetrias corporais, baixo índice de massa corporal e dificuldades alimentares. Há expectativa de alterações do desenvolvimento motor, da coordenação global e de fala. O presente estudo tem como objetivo apresentar características da síndrome, do neurodesenvolvimento e comunicação de três crianças do sexo masculino, com diagnóstico da síndrome, na faixa etária de 16, 18 e 44 meses, respectivamente. Cumpriram-se os critérios éticos. Foi realizada análise de prontuário, com objetivo de coletar informações da anamnese realizada com os responsáveis, e da avaliação realizada com as crianças. A avaliação foi realizada por meio da aplicação dos seguintes instrumentos: Observação do Comportamento Comunicativo (OCC), Teste de Screening de Desenvolvimento Denver-II (TSDD-II) e o Early Language Milestone Scale (ELMS). O levantamento de características confirmou a hipótese da SSR; na OCC verificou-se atraso nos comportamentos comunicativos para todos os participantes; no TSDD-II verificou-se atraso nas habilidades motora grossa, motora fina-adaptativa, linguagem e pessoal social. Na ELM verificou-se escores aquém do esperado para as funções auditiva receptiva e auditiva expressiva com habilidades receptivas mais desenvolvidas do que as habilidades expressivas. A SSR merece ser reconhecida pela comunidade científica, uma vez que as características fenotípicas e os dados de vida pregressa, possibilitam que seja levantada a hipótese da síndrome, visando o diagnóstico correto precocemente e um planejamento terapêutico que minimize os efeitos deletérios desta condição.

ABSTRACT Silver Russell Syndrome (SRS) is a genetically heterogeneous condition with a clinical phenotype that includes intrauterine and postnatal growth restriction, craniofacial alterations, body asymmetries, low body mass index, and feeding difficulties. Alterations in motor development, global coordination, and speech are expected. The current study aims to present the syndrome, neurodevelopment, and communication characteristics of three male children diagnosed with the syndrome, aged 16, 18, and 44 months, respectively. Ethical principles were followed. An analysis of the medical records, aiming to collect information of the anamnesis, conducted with the guardians, and of the assessment carried out with the children was performed. The assessment was performed by applying the following instruments: Communicative Behavior Observation (CBO), Development Screening Test Denver-II (TSDD-II), and the Early Language Milestone Scale (ELMS). The survey of characteristics confirmed the SRS hypothesis; it was verified a delay in communicative behavior for all participants in CBO; in TSDD-II there was a delay in gross motor, fine motor-adaptive, language, and social personal skills. Scores below expectations were found for receptive auditory and expressive auditory functions, with receptive abilities more developed than expressive abilities, in ELM. The SRS deserves to be recognized by the scientific community, since the phenotypic characteristics and the data from the previous life allow the hypothesis of the syndrome to be raised, aiming at an early correct diagnosis and therapeutic planning that minimizes the harmful effects of this condition.

Síndrome de Silver-Russell. Aspectos clínicos y etiopatológicos de una entidad ejemplo de impronta genómica / Silver-Russell syndrome. Clinical and etiopathological aspects of a model genomic imprinting entity

El síndrome de Silver-Russell se caracteriza por retraso del crecimiento intrauterino asimétrico, con circunferencia craneal normal, barbilla pequeña y puntiaguda, que proporciona un aspecto de rostro triangular. Puede, además, presentar asimetría corporal, entre otros. Tiene una incidencia mundial estimada de 1 en 30 000-100 000 nacimientos, aunque este número es, probablemente, subestimado. En alrededor del 60 % de los casos, se puede identificar una causa molecular y la principal es la hipometilación del alelo paterno en la región de control de impresión 1 localizado en 11p15.5-p15.4. Realizar el diagnóstico de esta entidad, excluir los diagnósticos diferenciales y conocer las correlaciones (epi)genotipo-fenotipo son necesarios para realizar el adecuado seguimiento, brindar las opciones terapéuticas disponibles y el oportuno asesoramiento genético familiar. El objetivo del presente artículo es mostrar el estado actual del síndrome de Silver-Russell, un ejemplo de trastorno de impronta genómica.

Silver-Russell syndrome is characterized by asymmetrical intrauterine growth retardation, with normal head circumference and small, pointed chin, which results in a triangular face. It can also include body asymmetry, among other characteristics. Its global incidence is estimated at 1 in 30 000-100 000 births, even though this figure may be underestimated. In approximately 60 % of cases, a molecular cause can be identified, and the main one is hypomethylation of the paternal allele at the imprinting control region 1 located at 11p15.5-p15.4. It is necessary to make the diagnosis of this entity, exclude differential diagnoses, and know (epi)genotype-phenotype correlations in order to ensure an adequate follow-up, provide available therapeutic options, and offer a timely family genetic counseling. The objective of this article is to describe the current status of the Silver-Russell syndrome, a model of genomic imprinting disorder.

A Clinico-Epidemiological Profile of Neuroparalytic Snake Bite, Using Low Dose ASV in a Tertiary Care Centre from Western Maharashtra

According to the World Health Organization, snakebites cause more death and disability and are more notorious than some tropical diseases. Snakebite is a leading medical emergency in Asia/Pacific. It is one of the major causes of mortality in India. The objective of this study was to determine the clinico-epidemiological profile of a neuroparalytic snake bite at the Department of Medicine, Krishna Institute of Medical Sciences, Karad, one of the tertiary care centers of Western Maharashtra, in India.METHODSA descriptive study of 80 patients was carried out at the Department of Medicine, KIMS, Karad, a tertiary care center of Western Maharashtra, India. Present study showed outcome, delay in arrival, and epidemiology of patients with low dose of ASV in neuroparalytic snakebites and ventilator support. Descriptive statistics were shown by using MS Excel and SPSS Version 25.RESULTSOut of 80 cases 56.2% were males and 43.8% were females with a mean age of 28.16 years. 63.7% of the snakebite victims were bitten outside and 85% of the snakebites occurred on the lower extremity. On an average, 15.24 vials of ASV were administered. 80% patient were in Intensive Care and they were on ventilator support and 91% patients recovered from these snake bites. 51.25% of the patients reached the hospital within the interval of 3-7 hours.CONCLUSIONSStudy signifies the importance of snakebite threat to the community. Delay in reaching a hospital in time where snakebite patients can be treated, was the most important cause of death. Public health programs should be strengthened. Administration of Low dose ASV and ventilator support can provide sufficient cure if patients reach on time. Lack of awareness, delay in reaching the hospital, and treatment by non-medical persons are important factors that should to be addressed.

Practice and performance of lupus anticoagulant tests: A single centre experience

@#Introduction: Lupus anticoagulant (LA) is a well-known risk factor for thrombosis. Correct diagnosis of LA is essential in patient management with anticoagulation. The objectives of this study were to document the clinical and laboratory characteristics of patients tested for LA and to evaluate existing LA testing methods in our laboratory with the aim of improving the performance of LA test interpretation and reporting. Methods: Tests for LA include dilute Russell’s viper venom time (dRVVT) and Kaolin clotting time (KCT). Patients with LA ratio (dRVVT screen ratio/dRVVT confirm ratio) of ≥1.2 were considered as LA positive irrespective of KCT results. KCT was considered positive if there was a prolongation in KCT screening test which was not corrected on mixing with normal plasma. Results: Of 577 patients’ results, 295 were normal, 178 were KCT positive with negative dRVVT and 104 were LA positive. Incidences of thrombosis, connective tissue disease (CTD) and bad obstetric events were noted in 13%, 16% and 44% of normal patients, 9%, 22% and 49% of KCT+ patients and 23%, 37% and 17% of LA+ patients respectively. On further evaluation of dRVVT screen ratios, 431 had a ratio of <1.1, 59 had a ratio between 1.1 and 1.2 and 87 had a ratio of >1.2. Positive LA results were found in 3%, 29% and 87% of patients with dRVVT screen ratios of <1.1, 1.1 - 1.2 and >1.2 respectively. Conclusion: LA+ patients had higher incidences of thrombosis and CTD as compared to normal and KCT only positive patients. There was no significant difference in clinical characteristics between normal and KCT+ patients which suggests the presence of a high rate of false-positive KCT results. Since confirmatory testing for KCT is not widely used, the option of using another LA screening test method should be considered. In regard to dRVVT testing, confirmatory test should only be performed in patients with prolonged dRVVT screening result which was not corrected upon mixing with normal plasma as required by the International Society of Thrombosis and Haemostasis guidelines on LA testing. This practice will not only result in significant cost reduction but also avoid diagnostic confusion.

Proteomics and antivenom immunoprofiling of Russell's viper (Daboia siamensis) venoms from Thailand and Indonesia

The Eastern Russell's viper, Daboia siamensis, is a WHO Category 1 medically important venomous snake. It has a wide but disjunct distribution in Southeast Asia. The specific antivenom, D. siamensis Monovalent Antivenom (DsMAV-Thailand) is produced in Thailand but not available in Indonesia, where a heterologous trivalent antivenom, Serum Anti Bisa Ular (SABU), is used instead. This study aimed to investigate the geographical venom variation of D. siamensis from Thailand (Ds-Thailand) and Indonesia (Ds-Indonesia), and the immunorecognition of the venom proteins by antivenoms. Methods: The venom proteins were decomplexed with reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by in-solution tryptic digestion, nano-liquid chromatography-tandem mass spectrometry and protein identification. The efficacies of DsMAV-Thailand and SABU in binding the various venom fractions were assessed using an enzyme-linked immunosorbent assay optimized for immunorecognition profiling. Results: The two most abundant protein families in Ds-Thailand venom are phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitor (KSPI). Those abundant in Ds-Indonesia venom are PLA2 and serine protease. KSPI and vascular endothelial growth factor were detected in Ds-Thailand venom, whereas L-amino acid oxidase and disintegrin were present in Ds-Indonesia venom. Common proteins shared between the two included snaclecs, serine proteases, metalloproteinases, phosphodiesterases, 5'nucleotidases and nerve growth factors at varying abundances. DsMAV-Thailand exhibited strong immunorecognition of the major protein fractions in both venoms, but low immunoreactivity toward the low molecular weight proteins e.g. KSPI and disintegrins. On the other hand, SABU was virtually ineffective in binding all fractionated venom proteins. Conclusion: D. siamensis venoms from Thailand and Indonesia varied geographically in the protein subtypes and abundances. The venoms, nevertheless, shared conserved antigenicity that allowed effective immunorecognition by DsMAV-Thailand but not by SABU, consistent with the neutralization efficacy of the antivenoms. A specific, appropriate antivenom is needed in Indonesia to treat Russell's viper envenomation.(AU)

Study of clinical and epidemiological profile of poisonous snake bite in a tertiary centre in North Kerala

Background: Snakebites are well-known medical emergencies in many parts of the world, especially in rural areas.The incidence of snakebite mortality is particularly high in South-East Asia. Rational use of snake anti-venom can substantially reduce mortality and morbidity due to snakebites. Snake bite is an important health problem in India also especially in North Kerala which has an agricultural background. There is a lack of study regarding this topic in this area. North Kerala differs from other areas in the country as hump nosed pit viper bites are more common here due to its proximity to western Ghats where it .Anti snake venom is ineffective to bites by hump nosed pit viper. Authors objectives  was to assess the clinical and epidemiological profile and outcome of poisonous snake bites.Methods: Retrospective observational study done among patients with snake bite with envenomation admitted in Academy of Medical education, Pariyaram, Kannur, Kerala from January 2018 to September 2018.Results: There were 90 cases of venomous snake bite during the study period. Of these males were predominant (70%). Majority were in the age group between 20 and 40. Majority of bites occurred in the months of June and July. Bite in the extremities were more common. Nine patients were brought 1 day after the bite. Snake identified most common was Russell’s viper followed by pit viper. Majority of the systemic envenomation was hemotoxic 80 patients (85%).Conclusions: The study stress the fact that snake bite is an important problem in North Kerala. The study also shows that delay in treatment is a major risk factor for morbidity. Hump nosed pit viper bites are more common in this area.

Clinical significance and pathological features of ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis / 中华肾脏病杂志

Objective To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN). Methods Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells. Results A total of 24 patients were enrolled in the study, including 21 males (87.5％), 3 females (12.5％). The age was (58.0 ± 10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7％) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2％) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028). Conclusions Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.

Clinical significance and pathological features of ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis / 中华肾脏病杂志

Objective@#To investigate the clinical significance and pathological features of lymphocytes and plasma cells infiltration and related ectopic lymphoid-like structures in IgG4-related tubulointerstitial nephritis (IgG4-TIN).@*Methods@#Complete data was collected from 24 patients with IgG4-TIN confirmed by pathology in the Peking University First Hospital. The renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy examination. In addition, immunohistochemistry was used to detect the distribution of CD20+ B lymphocytes, CD3+ T lymphocytes and CD138+ plasma cells.@*Results@#A total of 24 patients were enrolled in the study, including 21 males (87.5%), 3 females (12.5%). The age was (58.0±10.8) years (38-75 years). Pathology analysis showed ectopic lymphoid-like structures were located in 16 (66.7%) cases and Russell bodies were detected in infiltrative plasma cells of 19(79.2%) cases with IgG4-TIN. Compared with cases without Russell body formation, cases with Russell body formation in renal interstitial plasma cells were more prone to show ectopic germinal center-like structure formation (P=0.001), tubular basement membrane (TBM) electron dense deposits (P=0.040) and reduced blood C3 levels (P=0.028).@*Conclusions@#Abnormal tubulointerstitial infiltration of ectopic lymphoid-like structures and plasma cells with prominent Russell body exist in IgG4-TIN patients, which suggests the persistent activation of lymphocytes and plasma cells in renal interstitium may contribute to the pathogenesis of IgG4-TIN.

Stability of the hypocotyl length of soybean cultivars using neural networks and traditional methods / Estabilidade do comprimento do hipocótilo de plantas de cultivares de soja por meio de redes neurais e metodologias tradicionais

ABSTRACT: The length of the hypocotyl has been highlighted as a potential descriptor of the soybean crop. However, there is no information available in the published literature about its behavior over several planting times. The present study aimed to identify soybean cultivars with stability and predictability of hypocotyl length behavior through neural networks and traditional adaptability and stability methodologies. We analyzed 16 soybean cultivars in 6 planting seasons under greenhouse conditions. In each season, a randomized block design with 4 replications was adopted. The experimental unit was composed of 3 plants. The plot mean was used in the analysis. Hypocotyl length data were analyzed by analysis of variance and Tukey's test. Then analyses were carried out using the Traditional Method, Plaisted and Peterson, Wricke, Eberhart and Russell, and Artificial Neural Networks. A significant effect (p<0.01 by the F test) was identified for Cultivars versus Planting Season and Planting Seasons and Cultivars. Cultivars BRS810C, BRSMG760SRR, TMG1175RR, and BMX Tornado RR showed lower averages, high stability, and general adaptability regarding soybean hypocotyl length whereas the cultivar BG4272 presented higher mean, high stability, and general adaptability. Identification of soybean cultivars of predictable and stable behavior as to hypocotyl length contributes to Soybean Improvement as it further our knowledge on the potential descriptor and the possibility of increasing the number of descriptors.

RESUMO: O comprimento do hipocótilo tem-se destacado como potencial descritor da cultura da soja, no entanto, não se tem informação sobre o seu comportamento ao longo de várias épocas de plantio. Diante disto, objetivou-se identificar cultivares de soja com estabilidade e previsibilidade de comportamento quanto ao comprimento do hipocótilo por meio de redes neurais e metodologias tradicionais de adaptabilidade e estabilidade. Analisou-se 16 cultivares de soja em seis épocas de plantio, em condições de casa de vegetação. Em cada época, adotou-se o delineamento em blocos casualizados com quatro repetições, sendo a unidade experimental composta por três plantas e usou-se a média da parcela na análise. Os dados de comprimento de hipocótilo foram analisados por meio da análise de variância e teste de Tukey e, posteriormente, procedeu-se análises por meio do Método Tradicional, Plaisted e Peterson, Wricke, Eberhart e Russell e Redes Neurais Artificiais. Identificou-se efeito significativo (p<0,01 pelo teste F) para Cultivares x Épocas, Épocas e Cultivares. As cultivares BRS810C, BRSMG760SRR, TMG1175RR e BMX Tornado RR apresentaram menores médias, alta estabilidade e adaptabilidade geral quanto ao comprimento do hipocótilo de soja; enquanto que, a cultivar BG4272 apresentou maior média, alta estabilidade e adaptabilidade geral. A identificação de cultivares de soja de comportamento previsível e estável, quanto ao comprimento do hipocótilo, contribui para o Melhoramento da Soja no tocante ao melhor conhecimento do potencial descritor e à possibilidade de incremento do número de descritores.

Analysis of genetic defects in the 11p15.5 region in Russell-Silver syndrome / 临床儿科杂志

Objective To explore the pathogenesis of Russell-Silver syndrome (RSS). Methods Two milliliter peripheral blood samples were collected from 6 male patients aged 6 to 8 years with suspected RSS phenotype, the parents of 2 patients and 5 healthy boys. Mononuclear cells were isolated and genomic DNA was extracted. The methylation level of the H19 imprinting control region(ICR)1 on chromosome 11p15.5 was detected by pyrosequencing.The methylation status and the copy number variation in the corresponding region of one RSS patient with positive results by pyrosequencing were analysed by methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA). Results Pyrosequencing analysis revealed that the methylation rates on the 6 CpG targeting sites in H19 differentially methylated region(DMR)in the 6 RSS patients were about 11%~29%, which were significantly lower than those in their parents and normal controls (44%~59%). The MS-MLPA results of one patient with positive pyrosequencing showed that the methylation rates of 4 sites in H19-DMR were about 10%,which was obviously lower than the normal level.The methylation rates of the 4 sites in KCNQ1OT1 gene were about 50%, which was in the normal range. The copy number variations from all samples detected were in the normal range. Conclusion There is methylation aberration of H19-DMR in ICR1 in children with RSS.

Perfil Nutricional de Crianças Portadoras de Tumores Cerebrais com Síndrome Diencefálica ou Síndrome de Russell recebendo Dieta Enteral / Nutritional Profile of Children with Brain Tumor with Diencephalic Syndrome or Russell Syndrome receiving Enteral Diet / Perfil Nutricional de Niños Portadores de Tumores Cerebrales con Síndrome diencefálico o Síndrome de Russell recibiendo dieta Enteral

Introdução: a síndrome diencefálica é uma doença pediátrica rara, decorrente de tumores hipotalâmicos, caracterizada por failure to thrive. Objetivo: descrever o estado nutricional e a terapia nutricional por meio de sonda nasoenteral de pacientes com tumores cerebrais com a síndrome diencefálica. Método:sete pacientes foram acompanhados de julho/1999 a abril/2002 e analisados retrospectivamente, usando os escores-z de peso para idade (P/i), peso para estatura (P/e) e estatura para idade (e/i) no diagnóstico da desnutrição. todos foram avaliados por meio de composição corporal: prega cutânea triciptal (Pct) e circunferências do braço e muscular do braço (cB e cMB) e receberam alimentação por sonda nasoenteral ou gastrostomia após o diagnóstico da neoplasia. Resultados: a idade variou de 2 meses a 13 anos, cinco do sexo masculino. a duração média da nutrição enteral foi de 7 meses (1,1-18,5) após o diagnóstico, sem diferença estatística significante na evolução dos escores-z, apesar do aumento nas médias de P/i (-4,42 para -3,50) e P/e (-3,06 para -1,99), e dos indicadores de composição corporal (Pct: 2,85 para 4,88; cB: 9,81 para 11,84 e cMB: 8,91 para 10,31). Houve redução na média da e/i, caracterizando o atraso no crescimento dessas crianças. Conclusão: a nutrição enteral demonstrou garantir a oferta nutricional e recuperar em parte os indicadores nutricionais de desnutrição aguda; principalmente a gordura corporal, mais do que massa magra. entretanto, manteve-se o déficit de crescimento, agravado na maioria dos casos. a terapia nutricional deve ser implantada durante o tratamento oncológico, assegurando sua continuidade.

Introduction:diencephalic syndrome is a rare disorder of infancy characterized by profound emaciation with failure to thrive. The majority of cases of the syndrome are due to low grade gliomas of the anterior hypothalamus or optic nerve. Objective:to report the nutritional status and efficacy of nutritional support in patients with brain tumors that developed the russell's syndrome. Method:seven patients were retrospectively evaluated by means of z-score of the weight for age (W/a), weight for height (W/H) and height for age (H/a) nutritional status index, for protein-energy malnutrition diagnosis. They were evaluated by means of triceps skinfold thickness (tsFt), arm circumferences (ac) and muscle arm circumferences (Mac) and received enteral nutrition, by nasoenteral tube or gastrostomy at cancer diagnostic. Results: The ages ranged from 2 months to 13 years, five children were males. Mean of the nutritional support was 7 months (1.1-18.5 months) after diagnostic, without statistical differences in z-scores evolution, but there are increase in averages of the W/a (-4,42 to -3,50) and W/H (-3,06 to -1,99), and body composition indicators (tsFt): 2.85 to 4.88, ac: 9.81 to 11.84 and Mac: 8.91 to 10.31). There was decreased in average of H/a, evidencing the growth arrest of these children. Conclusion:enteral feeding has been shown to guarantee nutritional supply and to partially recover nutritional indicators of acute malnutrition; especially body fat, rather than lean mass. However, the growth deficit was not corrected, being aggravated in most cases. nutritional support should be implanted during oncological treatment, ensuring its maintenance.

Introducción:el síndrome diencefalica es una enfermedad pediátrica rara, derivada de tumores de la región hipotalámica, caracterizada por failure to thrive. Objetivo: describir condiciones nutricionales y terapia nutricional de pacientes con tumores cerebrales com síndrome diencefalica y nutrición enteral. Método: siete pacientes fueron acompañados de julio/1999 a abril/2002 y analizados retrospectivamente, usando el score-Z de peso para edad (P/i), peso para estatura (P/e) y estatura para edad (e/i) para el diagnóstico de la desnutrición. todos fueron evaluados por composición corporal (pliegue cutáneo triciptal y circunferencias del brazo y muscular del brazo). los pacientes recibieron nutrición enteral por sonda o gastrostomía, luego del diagnóstico de cancer. Resultados:la edad varía de 2 meses a 13 años, cinco del sexo masculino. la duración media de la nutrición enteral fue de 7 meses (1,1-18,5) después del diagnóstico. no hubo diferencia estadística en la evolución nutricional, a pesar del aumento en P/i (-4,42 a -3,50) y P/e (-3,06 a -1,99), así como en la composición corporal (Pct: 2,85 a 4,88, cB: 9,81 a 11,84 y cMB: 8,91 para 10.31). Hubo una reducción de e/i, caracterizando el retraso en el crecimiento. Conclusión:la nutrición enteral demostró garantizar la oferta nutricional.e la recuperación parcial de la desnutrición aguda, principalmente grasa corporal, más que masa magra, sin respuesta al déficit en el crecimiento, que se agravó en casi todos los casos. la terapia nutricional debe ser implantada durante el tratamiento oncológico, asegurando su continuidad.

Síndrome de Silver-Russell, un desafío diagnóstico / Silver-russell syndrome, a diagnostic challenge

El síndrome de Silver-Russell es una condición infrecuente que clínicamente se manifiesta por macrocefalia relativa, dismorfias faciales, restricción importante de crecimiento pre-y postnatal y otros hallazgos variables al examen físico. En un 60% de los pacientes el estudio genético actualmente disponible permite establecer el diagnostico, sin embargo prevalecen los criterios clínicos. Se presenta el caso clínico de un paciente evaluado al año de vida con historia de restricción de crecimiento prenatal y con talla baja y desnutrición crónica descompensada, en el cuál se descartaron otras etiologías y se concluye por criterios clínicos de padecer el síndrome, a pesar de un estudio genético negativo. Debido a un amplio espectro de manifestaciones clínicas a veces sutiles y confundentes se debe conocer este síndrome para su diagnóstico oportuno.

Silver-Russell syndrome is an uncommon condition that manifests itself as relative macrocephaly, facial dysmorphia, poor pre-and post-natal growth and other variable physical features. In 60% of patients it is possible to establish the diagnosis through available genetic testing; however, clinical criteria are more important. We present the clinical case of a patient with poor pre-natal growth, small size and chronic malnutrition evaluated at one year old where other etiologies were discounted and the syndrome diagnosed because of the clinical signs, despite genetic tests being negative. With its ample spectrum of sometimes subtle and confusing clinical signs, familiarity with this syndrome is key to reaching an early diagnosis.

Laboratory measurement of bleeding risk for patients receiving Dabigatran / 临床检验杂志

Objective To observe the correlation between conventional coagulation tests and Dabigatran concentration in order to find proper test method to predict the bleeding risk of patients receiving Dabigatran.Methods The clinical data of forty-nine non-valvular atrial fibrillation (NVAF) patients who took Dabigatran in Peking University Third Hospital from 2015 to 2017 were analyzed and the bleeding rates were calculated.The plasma samples from twenty healthy volunteers were collected and mixed up into normal pooled plasma (NPP).Different doses of active Dabigatran were mixed with NPP,making Dabigatran concentrations from 0 to 1 000 ng/mL.Prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),fibrinogen (Fib) and diluted Russell viper venom time (dRVVT) were determined.Fresh whole blood samples from three normal volunteers were collected and mixed with Dabigatran in the same way to perform thromboelastogram (TEG).Results The total bleeding rate of NVAF patients receiving Dabigatran was 28.6％,among which gastrointestinal bleeding accounts for the most.APTT,dRVVT,R time (R) and clot index (CI) showed a good linear correlation with Dabigatran concentration.The sensitivity of dRVVT was the best,followed by APTT.R and CI showed low sensitivity compared with APTT and dRVVT.Conclusion APTT and dRVVT should be good parameters for monitoring the bleeding risk of Dabigatran and helpful for physicians to choose proper point-in-time for withdrawal of Dabigatran and reduce bleeding events.

Russell Body Gastritis Disappeared after Helicobacter pylori Eradication

A rare gastric mucosal lesion characterized by Russell body-containing plasma cell infiltration is termed as Russell body gastritis. This lesion is highly suggested to be correlated with Helicobacter pylori-induced chronic gastritis, and often misdiagnosed as mucosa-associated lymphoid tissue lymphoma, signet ring cell carcinoma, plasmacytoma, or xanthoma. However, Russell body gastritis is easily discriminated by its polyclonal immunoreaction to immunoglobulin light chains contrary to monoclonal immunoreaction of neoplastic disease. We report here a case of Russell body gastritis associated with H. pylori infection, which disappeared after H. pylori eradication.

Dabigatran en plasma: tiempos de trombina diluido, Ecarin y veneno de víbora de Russell diluido / Plasma dabigatran: diluted thrombin time, Ecarin and diluted Russell Viper Venom Time / Dabigatrana em plasma: tempos de trombina diluído, Ecarin e veneno de víbora de Russell diluído

Los objetivos del trabajo fueron verificar la calidad analítica del ensayo tiempo de trombina diluido (DTI) para medición de la concentración plasmática (cc) de dabigatran comparando dos coagulómetros de detección foto-óptica, comparar los resultados con el tiempo de Ecarin (ECT) y correlacionar las cc con las pruebas básicas de coagulación Tiempo de protrombina (TP), APTT y Tiempo de trombina (TT), y tiempo de veneno de víbora de Russell con fosfolípidos concentrados (DRVVTC). Se tomaron 43 muestras de plasma en el valle (10-14 h de la última toma) de 40 pacientes que recibían dabigatran. DTI y ECT presentaron (%) repetitividad <5,4% y <7,5%, CV interensayo <6% y <9%, respectivamente, en el protocolo EP15A2, aceptables para un Error Total permitido (TEa) <15%. Las cc medidas en pacientes fueron: mediana 83 (4-945) ng/mL. La comparación de equipos ACL TOP 300 y 500 dio resultados equivalentes por procedimiento alternativo de comparación de métodos. La comparación ECT vs. DTI fue satisfactoria por regresión de Deming (pendiente 1,143, ordenada al origen -19,33). Las correlaciones de cc vs. APTT, TP y DRVVTC fueron moderadas y no lineales tendiendo a plateau a cc>350 ng/mL, r2 0,59, 0,66 y 0,59, respectivamente. El TT fue extremadamente sensible: >120 s a cc 50 ng/mL. DTI presentó un buen desempeño analítico y permitió cuantificar dabigatran plasmático a cc bajas y altas en ambos equipos utilizados. ECT presentó resultados comparables a DTI. Se verifica una correlación moderada entre cc de dabigatran y las pruebas clásicas y DRVVTC, pudiendo ser estimadores de cc a partir de los 50 ng/mL.

The aims of the study were to verify the analytical performance of Dilute Thrombin Time (DTI) test to measure plasma dabigatran concentration (cc) in two photo-optical coagulometers, compare Ecarin clotting Time (ECT) and DTI results, and correlate cc with classical coagulation tests: prothrombin time (PT), APTT, thrombin time (TT) and diluted Russell Viper Venom Time tests with high phospholipid concentration (DRVVTC). Forty three plasma samples from 40 patients taking dabigatran were drown at through (10-14 hs.since last dose). DTI and ECT showed repetitivity (%) <5.4% and <7.5%, interassay CV <6% and <9%, respectively, following EP15A2 protocol, acceptable considering a Allowed Total Error (TEa)<15%. Patients` cc: median 83 (4-945) ng/mL. The comparison between ACL TOP 300 and 500 coagulometers showed equivalent results by using the alternative method comparison test. ECT vs. DTI: acceptable by Deming`s regression (slope 1.143, Y insert -19.33). cc vs. APTT, TP and DRVVTC: nonlinear and moderate correlations with plateau reached at cc >350 ng/mL, r2 0.59, 0.66 y 0.59, respectively. TT is extremely prolonged at cc >50 ng/mL. In conclusion: DTI showed a good analytical performance in both coagulometers. ECT showed comparable results to DTI. We verified that dabigatran cc presented moderate correlations with PT, APTT and DRVVTC, and that these tests could only qualitative estimate cc >50 ng/mL.

Os objetivos do trabalho foram verificar a qualidade analítica do ensaio tempo de trombina diluído (DTI) para medição da concentração plasmática (cc) de dabigatrana, comparando dois coagulômetros de detecção foto-óptica, comparar os resultados com o tempo de Ecarina (ECT) e correlacionar as cc com os testes básicos de coagulação Tempo de protrombina (TP), APTT e Tempo de trombina (TT), e tempo de veneno de víbora de Russell com fosfolipídios concentrados (DRVVTC). Foram tomadas 43 amostras de plasma no vale (10-14 h. da última toma) de 40 pacientes que recebiam dabigatrana. DTI e ECT apresentaram (%) repetitividade <5,4% e <7,5%, CV interensaio <6% e <9%, respectivamente, no protocolo EP15A2, aceitáveis para um Erro Total permitido (TEa) <15%. Cc medidas em pacientes: mediana 83 (4-945) ng/mL. Comparação de equipamentos ACL TOP 300 e 500: resultados equivalentes por procedimento alternativo de comparação de métodos. Comparação ECT vs. DTI: satisfatória por regressão de Deming (pendente 1,143, ordenada à origem -19,33). Correlações cc vs. APTT, TP e DRVVTC: moderadas e não lineares tendendo a plateau a cc>350 ng/mL, r2 0,59; 0,66 e 0,59, respectivamente. O TT é extremamente sensível: >120 s a cc 50 ng/mL. DTI apresentou um bom desempenho analítico e permitiu quantificar dabigatrana plasmática a cc baixas e altas em ambos os equipamentos utilizados. ECT apresentou resultados comparáveis com DTI. Verifica-se uma correlação moderada entre cc de dabigatrana e os testes clássicos e DRVVTC, podendo ser estimadores de cc a partir dos 50 ng/mL.

Chronological Endoscopic and Pathological Observations in Russell Body Duodenitis

A 64-year-old man was found to have a nodule in his right lung. He also complained of nausea and abdominal pain during the clinical course. Esophagogastroduodenoscopy revealed a duodenal ulcer associated with severe stenosis and a suspicion of malignancy. However, three subsequent biopsies revealed no evidence of malignancy. The fourth biopsy showed scattered large eosinophilic cells with an eccentric nucleus, leading to a diagnosis of Russell body duodenitis (RBD). RBD is an extremely rare disease, and little is known about its etiology and clinical course. The pathogenesis of RBD is discussed based on our experience with this case.

Challenges in diagnosis and management of snake bites in resource poor settings: A case report of suspected Russell’s viper envenomation.

Snake bite is a common and neglected problem resulting in a large global mortality and morbidity per year. In India alone, an estimated 45,900 deaths occur per annum. The outlined case of suspected Russell’s Viper (Daboia russelii) envenomation occurred in rural West Bengal. The case was misdiagnosed on two occasions resulting in a substantial delay in antivenom therapy. The resultant delay contributed to a significant morbidity and prolonged hospital admission. The case report illustrates some practical difficulties faced by clinicians pertaining to diagnosis, complications and resource limitations. These areas are discussed with a view to improving awareness and management. Simple practical tools are included to assist a clinician faced with snake bites in South Asia.

Símdrome de Silver-Russell (hemihipertrofia) y cor triatriatum en un neonato / Silver-Russell syndrome (hemihypertrophy) and cor triatriatum in a newborn

Tanto el síndrome de hemihipertrofia como el cor triatriatum son patologías sumamente infrecuentes. La hemihipertrofia se define como el sobrecrecimiento completo o parcial de uno de los hemicuerpos. El cor triatriatum es una cardiopatía congénita caracterizada por una membrana que divide la aurícula izquierda en dos cámaras; si esta membrana tiene un orificio restrictivo, provoca obstrucción al pasaje sanguíneo desde las venas pulmonares hacia el ventrículo izquierdo, lo que genera hipertensión y edema pulmonar. En este contexto, el ductus arterioso permeable puede actuar como vía de descompresión del circuito pulmonar al permitir el pasaje sanguíneo desde la arteria pulmonar hacia la aorta. Presentamos a un paciente con diagnóstico de síndrome de Silver-Rusell (hemihipertrofia), cor triatriatum y ductus arterioso con flujo invertido. Hasta donde conocemos, esta asociación de patologías infrecuentes y forma de presentación no se han descrito anteriormente.

Hemihypertrophy syndrome and cor triatriatum are extremely rare pathologies. Hemihypertrophy is defined as complete or partial overgrowth of one of the hemibodies. Cor triatriatum is a congenital heart disease characterized by a membrane which separates the left atrium into two chambers; if that membrane has a restrictive hole, it causes obstruction to blood passage from the pulmonary veins into the left ventricle causing hypertension and pulmonary edema. In this context, the patent ductus arteriosus can act as a means of decompression of the pulmonary circuit, because it allows the blood passage from the pulmonary artery to the aorta. We report a patient with Silver-Rusell syndrome (hemihypertrophy), cor triatriatum and ductus arteriosus with reverse flow. To our knowledge, this association of rare pathologies and this clinical presentation have not been described previously.

Prosthetic management of a growing patient with Russell-Silver syndrome: a clinical report

Russell-Silver syndrome (RSS) is a congenital disease characterized by short stature due to growth hormone deficiency, physical asymmetry, inverted triangular face, micrognathia, prominent forehead, and hypodontia. This case report presents a prosthetic management of a 6-year-old patient with Russell-Silver syndrome treated with overdentures on the maxilla and the mandible using the remaining primary teeth. Subsequent and comprehensive dental management considering the growth and development of a young patient will be necessary.