RESUMO
In Mozambique, targeted provider-initiated HIV testing and counselling (PITC) is recommended where universal PITC is not feasible, but its effectiveness depends on healthcare providers' training. This study aimed to evaluate the effect of a Ministry of Health training module in targeted PITC on the HIV positivity yield, and identify factors associated with a positive HIV test. We conducted a single-group pre-post study between November 2018 and November 2019 in the triage and emergency departments of four healthcare facilities in Manhiça District, a resource-constrained semi-rural area. It consisted of two two-month phases split by a one-week targeted PITC training module ("observation phases"). The HIV positivity yield of targeted PITC was estimated as the proportion of HIV-positive individuals among those recommended for HIV testing by the provider. Additionally, we extracted aggregated health information system data over the four months preceding and following the observation phases to compare yield in real-world conditions ("routine phases"). Logistic regression analysis from observation phase data was conducted to identify factors associated with a positive HIV test. Among the 7,102 participants in the pre- and post-training observation phases (58.5% and 41.5% respectively), 68% were women, and 96% were recruited at triage. In the routine phases with 33,261 individuals (45.8% pre, 54.2% post), 64% were women, and 84% were seen at triage. While HIV positivity yield between pre- and post-training observation phases was similar (10.9% (269/2470) and 11.1% (207/1865), respectively), we observed an increase in yield in the post-training routine phase for women in triage, rising from 4.8% (74/1553) to 7.3% (61/831) (Yield ratio = 1.54; 95%CI: 1.11-2.14). Age (25-49 years) (OR = 2.43; 95%CI: 1.37-4.33), working in industry/mining (OR = 4.94; 95%CI: 2.17-11.23), unawareness of partner's HIV status (OR = 2.50; 95%CI: 1.91-3.27), and visiting a healer (OR = 1.74; 95%CI: 1.03-2.93) were factors associated with a positive HIV test. Including these factors in the targeted PITC algorithm could have increased new HIV diagnoses by 2.6%. In conclusion, providing refresher training and adapting the current targeted PITC algorithm through further research can help reach undiagnosed PLHIV, treat all, and ultimately eliminate HIV, especially in resource-limited rural areas.
Assuntos
Humanos , Masculino , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Aconselhamento , Triagem/métodos , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Serviço Hospitalar de Emergência , Moçambique/epidemiologiaRESUMO
PURPOSE: Gilteritinib is a type 1 FLT3 inhibitor active as monotherapy for relapsed or refractory FLT3-mutated AML. We investigated the safety, tolerability, and efficacy of gilteritinib incorporated into intensive induction and consolidation chemotherapy, and as maintenance therapy for adult patients with newly diagnosed, non-favorable-risk AML. METHODS: In this phase IB study (2215-CL-0103; ClinicalTrials.gov identifier: NCT02236013), 103 participants were screened and 80 were allocated to treatment. The study was divided into four parts: dose escalation, dose expansion, investigation of alternate anthracycline and gilteritinib schedule, and continuous gilteritinib during consolidation. RESULTS: After dose escalation, 120 mg gilteritinib once daily was chosen for further study. There were 58 participants evaluable for response at this dose, 36 of whom harbored FLT3 mutations. For participants with FLT3-mutated AML, the composite complete response (CRc) rate was 89% (83% were conventional complete responses), all achieved after a single induction cycle. The median overall survival time was 46.1 months. Gilteritinib was well-tolerated in this context although the median time to count recovery during induction was approximately 40 days. Longer time-to-count recovery was associated with higher trough levels of gilteritinib, which, in turn, were associated with azole use. The recommended regimen is gilteritinib at a dose of 120 mg once daily from days 4 to 17 or 8 to 21 of a 7 + 3 induction with either idarubicin or daunorubicin and from day 1 continuously with high-dose cytarabine consolidation. Maintenance therapy with gilteritinib was well-tolerated. CONCLUSION: These results demonstrated the safety and tolerability of gilteritinib incorporated into an induction and consolidation chemotherapy regimen, and as single-agent maintenance therapy for patients with newly diagnosed FLT3-mutant AML. The data herein provide an important framework for the design of randomized trials comparing gilteritinib with other FLT3 inhibitors.
Assuntos
Quimioterapia de Consolidação , Leucemia Mieloide Aguda , Adulto , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Idarubicina , Inibidores de Proteínas Quinases/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , MutaçãoAssuntos
COVID-19 , Febre de Chikungunya , Dengue , Humanos , Febre de Chikungunya/epidemiologia , Paraguai , Dengue/epidemiologia , Surtos de DoençasRESUMO
PURPOSE: To investigate the opinions of physicians on the use of complementary and alternative medicine (CAM) in patients with epilepsy (PWE) worldwide. METHODS: Online survey addressed to neurologists and psychiatrists from different countries. RESULTS: Totally, 1112 physicians from 25 countries (different world region: Europe, North America, South America, Middle-East, Africa, Former Soviet Union Republics) participated; 804 (72.3%) believed that CAM might be helpful in PWE. The most commonly endorsed CAM included meditation (41%) and yoga (39%). Female sex, psychiatry specialization, and working in North and South America were associated with the belief that CAM is helpful in PWE. Two-hundred and forty five out of 1098 participants (22.3%) used/prescribed CAM to PWE; among them, 174 (71%) people perceived CAM to be less effective and 114 (46.5%) people found CAM to be safer than conventional antiseizure medications (ASMs). The most common reasons to prescribe CAM for PWE were: to satisfy the patient (49.9%), dissatisfaction with the efficacy (35.6%), and dissatisfaction with the adverse effects (31.2%) of conventional therapies. CONCLUSION: Although the evidence supporting the use of CAM for the treatment of epilepsy is extremely sparse, most physicians worldwide believe that it could be integrated with the use of conventional ASMs, at least in some patients. High-quality controlled trials are warranted to provide robust evidence on the usefulness of CAM options in PWE.
Assuntos
Terapias Complementares , Epilepsia , Médicos , África , Epilepsia/terapia , Europa (Continente) , Feminino , Humanos , Oriente Médio , América do Norte , América do Sul , Inquéritos e QuestionáriosRESUMO
Complement plays important roles in both ischemia-reperfusion injury (IRI) and antibody-mediated rejection (AMR) of solid organ allografts. One approach to possibly improve outcomes after transplantation is the use of C1 inhibitor (C1-INH), which blocks the first step in both the classical and lectin pathways of complement activation and also inhibits the contact, coagulation, and kinin systems. C1-INH can also directly block leukocyte-endothelial cell adhesion. C1-INH contrasts with eculizumab and other distal inhibitors, which do not affect C4b or C3b deposition or noncomplement pathways. Authors of reports on trials in kidney transplant recipients have suggested that C1-INH treatment may reduce IRI and delayed graft function, based on decreased requirements for dialysis in the first month after transplantation. This effect was particularly marked with grafts with Kidney Disease Profile Index ≥ 85. Other clinical studies and models suggest that C1-INH may decrease sensitization and donor-specific antibody production and might improve outcomes in AMR, including in patients who are refractory to other modalities. However, the studies have been small and often only single-center. This article reviews clinical data and ongoing trials with C1-INH in transplant recipients, compares the results with those of other complement inhibitors, and summarizes potentially productive directions for future research.
Assuntos
Ativação do Complemento/efeitos dos fármacos , Proteína Inibidora do Complemento C1/uso terapêutico , Complemento C1s/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Função Retardada do Enxerto/prevenção & controle , Rejeição de Enxerto/prevenção & controle , Transplante de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Aloenxertos , Animais , Proteína Inibidora do Complemento C1/efeitos adversos , Complemento C1s/imunologia , Inativadores do Complemento/efeitos adversos , Função Retardada do Enxerto/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Órgãos/efeitos adversos , Traumatismo por Reperfusão/imunologia , Fatores de Risco , Resultado do TratamentoRESUMO
Nitric oxide (NO) is a key regulator of skeletal muscle function and metabolism, including vasoregulation, mitochondrial function, glucose uptake, fatigue and excitation-contraction coupling. The main generator of NO in skeletal muscle is the muscle-specific form of neuronal nitric oxide synthase (nNOSµ) produced by the NOS1 gene. Skeletal muscle nNOSµ is predominantly localized at the sarcolemma by interaction with the dystrophin protein complex (DPC). In Duchenne muscular dystrophy (DMD), loss of dystrophin leads to the mislocalization of nNOSµ from the sarcolemma to the cytosol. This perturbation has been shown to impair contractile function and cause muscle fatigue in dystrophic (mdx) mice. Here, we investigated the effect of restoring sarcolemmal nNOSµ on muscle contractile function in mdx mice. To achieve this, we designed a modified form of nNOSµ (NOS-M) that is targeted to the sarcolemma by palmitoylation, even in the absence of the DPC. When expressed specifically in mdx skeletal muscle, NOS-M significantly attenuates force loss owing to damaging eccentric contractions and repetitive isometric contractions (fatigue), while also improving force recovery after fatigue. Expression of unmodified nNOSµ at similar levels does not lead to sarcolemmal association and fails to improve muscle function. Aside from the benefits of sarcolemmal-localized NO production, NOS-M also increased the surface membrane levels of utrophin and other DPC proteins, including ß-dystroglycan, α-syntrophin and α-dystrobrevin in mdx muscle. These results suggest that the expression of NOS-M in skeletal muscle may be therapeutically beneficial in DMD and other muscle diseases characterized by the loss of nNOSµ from the sarcolemma.
Assuntos
Contração Muscular , Óxido Nítrico Sintase Tipo I/metabolismo , Sarcolema/metabolismo , Animais , Proteínas Associadas à Distrofina/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Óxido Nítrico Sintase Tipo I/genética , Utrofina/metabolismoRESUMO
BACKGROUND: Pertussis is among the most poorly controlled bacterial vaccine-preventable diseases in the United States. In 2006, a tetanus, reduced-dose diphtheria, and acellular pertussis (Tdap) booster was recommended for adolescents and adults. Tdap vaccines were licensed on the basis of antibody response without vaccine effectiveness data. METHODS: From 30 September 2007 through 19 December 2007, a pertussis outbreak occurred at a nursery through twelfth grade school on St. Croix, US Virgin Islands. We screened all students for cough and collected clinical history, including Tdap receipt. Coughing students were offered diagnostic testing. We defined clinical case patients as students with cough 14 days in duration plus either whoop, paroxysms, or post-tussive vomiting, and we defined confirmed case patients as students with any cough with isolation of Bordetella pertussis or those with clinical cases and polymerase chain reaction or serological evidence of pertussis; other clinical cases were classified as probable. RESULTS: There were 51 confirmed or probable cases among 499 students (attack rate, 10%). Disease clustered in grades 6-12, with a peak attack rate of 38% among 10th graders. Of 266 students aged 11 years with complete data, 31 (12%) had received Tdap. Forty-one unvaccinated students (18%) had confirmed or probable pertussis, compared with 2 (6%) of the vaccinated students (relative risk, 2.9); vaccine effectiveness was 65.6% (95% confidence interval, -35.8% to 91.3%; P = .092). CONCLUSIONS: This first evaluation of Tdap vaccine effectiveness in the outbreak setting suggests that Tdap provides protection against pertussis. Increased coverage is needed to realize the full benefit of the vaccine program. Serological testing was an important tool for case identification and should be considered for inclusion in the Council of State and Territorial Epidemiologists case definition.
Assuntos
Bordetella pertussis/imunologia , Bordetella pertussis/isolamento & purificação , Vacinas contra Difteria, Tétano e Coqueluche Acelular/administração & dosagem , Vacinas contra Difteria, Tétano e Coqueluche Acelular/imunologia , Surtos de Doenças , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Nasofaringe/microbiologia , Reação em Cadeia da Polimerase , Ilhas Virgens Americanas/epidemiologia , Vacinação/estatística & dados numéricos , Adulto JovemRESUMO
Bacterial strains UST030701-097T and UST030701-084T were isolated from a marine sponge in the Bahamas. Both strains were pink-pigmented, Gram-negative, strictly aerobic and chemo-organotrophic. Cells of strain UST030701-097T were short, curved rods with fast-gliding motility, whereas those of strain UST030701-084T were straight rods with a less rapid gliding motion. The two strains had MK-7 as the major respiratory quinone and did not produce flexirubin-type pigments. The DNA G+C contents of strains UST030701-097T and UST030701-084T were 42.5 and 43.7 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains belonged to the family 'Flexibacteraceae' of the phylum Bacteroidetes. 16S rRNA gene sequence similarity between strains UST030701-097T and UST030701-084T was 95.0 %; their closest relative was [Marinicola] seohaensis, with 93.3 % and 96.0 % sequence similarity, respectively. Phylogenetic tree topology indicated that the two strains belonged to the same lineage, but were on separate branches. Whilst strain UST030701-084T and [Marinicola] seohaensis were found on one branch, strain UST030701-097T was in another branch that had no species with validly published names. Based on the polyphasic taxonomic data obtained in the present study, we propose that strain UST030701-097T represents a novel genus and that strain UST030701-084T represents a novel species in the phylum Bacteroidetes. The genus Fabibacter gen. nov. is proposed, with strain UST030701-097T (=NRRL B-41220T=JCM 13334T) as the type strain of the type species, Fabibacter halotolerans sp. nov. Strain UST030701-084T (=NRRL B-41219T=JCM 13337T) is proposed as the type strain of Roseivirga spongicola sp. nov. In an earlier study, it was suggested that the genus Marinicola is a later heterotypic synonym of the genus Roseivirga. However, a formal proposal to reclassify [Marinicola] seohaensis, the only member of the genus Marinicola, has not yet been made. The results of phylogenetic analyses in this study support the reclassification of [Marinicola] seohaensis as Roseivirga seohaensis comb. nov.
Assuntos
Cytophagaceae/classificação , Cytophagaceae/isolamento & purificação , Poríferos/microbiologia , Aerobiose , Animais , Técnicas de Tipagem Bacteriana , Bahamas , Composição de Bases , Cytophagaceae/citologia , Cytophagaceae/fisiologia , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Genes de RNAr , Violeta Genciana , Biologia Marinha , Dados de Sequência Molecular , Movimento , Fenazinas , Filogenia , Pigmentos Biológicos/biossíntese , Polienos/análise , Quinonas/análise , Quinonas/isolamento & purificação , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
A bacterial strain, UST030701-156T, was isolated from a marine sponge in the Bahamas. Strain UST030701-156T was orange-pigmented, Gram-negative, rod-shaped with tapered ends, slowly motile by gliding and strictly aerobic. The predominant fatty acids were a15 : 0, i15 : 0, i15 : 0 3-OH, i17 : 0 3-OH, i17 : 1omega9c and summed feature 3, comprising i15 : 0 2-OH and/or 16 : 1omega7c. MK-6 was the only respiratory quinone. Flexirubin-type pigments were not produced. Phylogenetic analysis based on 16S rRNA gene sequences placed UST030701-156T within a distinct lineage in the family Flavobacteriaceae, with 93.3 % sequence similarity to the nearest neighbour, Nonlabens tegetincola. The DNA G+C content of UST030701-156T was 41.0 mol% and was much higher than that of N. tegetincola (33.6 mol%). Strain UST030701-156T can be distinguished from other members of the Flavobacteriaceae by means of a number of chemotaxonomic and phenotypic characteristics. It is proposed, therefore, that UST030701-156T represents a novel taxon designated Stenothermobacter spongiae gen. nov., sp. nov. The type strain is UST030701-156T (= NRRL B-41138T = JCM 13191T). Carbon-source utilization by N. tegetincola was re-examined and an emended description is therefore included.
Assuntos
Flavobacteriaceae/classificação , Poríferos/microbiologia , Água do Mar/microbiologia , Aerobiose , Animais , Bahamas , Composição de Bases , Carbono/metabolismo , Ácidos Graxos , Flavobacteriaceae/química , Flavobacteriaceae/isolamento & purificação , Flavobacteriaceae/fisiologia , Dados de Sequência Molecular , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Vitamina K 2/análogos & derivadosRESUMO
A Gram-negative, rod-shaped bacterium (designated strain UST030701-295(T)) with fast gliding motility was isolated from the surface of the sponge Lissodendoryx isodictyalis in the Bahamas. Colonies of UST030701-295(T) were yellow in colour, 2-4 mm in diameter, convex with a smooth surface and entire margins. UST030701-295(T) was heterotrophic, strictly aerobic and required NaCl for growth (1.0-4.0%). Growth was observed at pH 6.0-10.0 and at 12-44 degrees C. Phylogenetic analysis of the 16S rRNA gene sequence placed UST030701-295(T) within the genus Winogradskyella of the family Flavobacteriaceae, sharing 94.7-95.8% similarity with the three recognized members of the genus. The G+C content of the DNA was 32.8 mol% and the predominant fatty acids were iso-C(15:1), iso-C(15:0), iso-C(15:0) 2-OH, iso-C(15:0) 3-OH, iso-C(16:0) 3-OH, C(16:1)omega7 and iso-C(17:0) 3-OH (together representing 75.4% of the total); these data supported the affiliation of UST030701-295(T) to the genus Winogradskyella. UST030701-295(T) differed from the three recognized species of Winogradskyella in 7-17 traits. Molecular evidence together with phenotypic characteristics suggests that UST030701-295(T) represents a novel species within the genus Winogradskyella, for which the name Winogradskyella poriferorum sp. nov. is proposed. The type strain is UST030701-295(T) (=NRRL B-41101(T)=JCM 12885(T)).
Assuntos
Flavobacteriaceae/classificação , Poríferos/microbiologia , Animais , Técnicas de Tipagem Bacteriana , Bahamas , Composição de Bases , DNA Bacteriano/análise , DNA Ribossômico/análise , Flavobacteriaceae/genética , Flavobacteriaceae/isolamento & purificação , Flavobacteriaceae/fisiologia , Genes de RNAr , Dados de Sequência Molecular , Fenótipo , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Especificidade da EspécieRESUMO
Los autores postulan que metodológicamente las hipótesis sobre el preconsciente constituyen el camino para operacionalizar la teoría sobre la sexualidad en su carácter diferencial (oral, anal, etc.) Tras definir el preconsciente, se refieren a su proceso de constitución y a su organización interna, una vez constituido. Los autores se proponen considerar el pasaje de las hipótesis sobre la estructura del preconsciente hasta las manifestaciones. Destacan, además, que en cada organización clínica prevalece un tipo de fijación libidinal, la cual se expresa en ciertos rasgos específicos del preconsciente y consiguientemente del lenguaje. Exponenen entonces un método que permite investigar el discurso de los pacientes como expresión de la erogeneidad. El método (algoritmo David Liberman) permite estudiar la erogeneidad en tres niveles del lenguaje: palabra, frase y relato. Los autores describen las características de los instrumentos empleados para investigar cada uno de estos tres niveles: una grilla para el relato, dos grillas para las frases, y un programa computacional (diccionario) para las palabras. Se refieren también a algunos problemas metodológicos e instrumentales y consideran cuestiones ligadas con el valor de cada uno de estos niveles de análisis en relación con los otros dos
Assuntos
Idioma , PsicanáliseRESUMO
Los autores postulan que metodológicamente las hipótesis sobre el preconsciente constituyen el camino para operacionalizar la teoría sobre la sexualidad en su carácter diferencial (oral, anal, etc.) Tras definir el preconsciente, se refieren a su proceso de constitución y a su organización interna, una vez constituido. Los autores se proponen considerar el pasaje de las hipótesis sobre la estructura del preconsciente hasta las manifestaciones. Destacan, además, que en cada organización clínica prevalece un tipo de fijación libidinal, la cual se expresa en ciertos rasgos específicos del preconsciente y consiguientemente del lenguaje. Exponenen entonces un método que permite investigar el discurso de los pacientes como expresión de la erogeneidad. El método (algoritmo David Liberman) permite estudiar la erogeneidad en tres niveles del lenguaje: palabra, frase y relato. Los autores describen las características de los instrumentos empleados para investigar cada uno de estos tres niveles: una grilla para el relato, dos grillas para las frases, y un programa computacional (diccionario) para las palabras. Se refieren también a algunos problemas metodológicos e instrumentales y consideran cuestiones ligadas con el valor de cada uno de estos niveles de análisis en relación con los otros dos (AU)
Assuntos
Idioma , PsicanáliseRESUMO
Dumping syndrome and postprandial hypoglycemia have been reported after Nissen fundoplication. The physiopathologic mechanisms are poorly understood and a variety of therapies have failed to control the hypoglycemia in these patients. We report a series of 6 infants with postprandial hypoglycemia after Nissen fundoplication who were treated successfully with acarbose.
Assuntos
Acarbose/uso terapêutico , Fundoplicatura/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Hipoglicemia/tratamento farmacológico , Hipoglicemia/etiologia , Hipoglicemiantes/uso terapêutico , Período Pós-Prandial/efeitos dos fármacos , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
OBJECTIVE: Because the hyperinsulinism/hyperammonemia (HI/HA) syndrome is associated with gain of function mutations in the leucine-stimulated insulin secretion pathway, we examined whether protein feeding or fasting was responsible for hypoglycemia in affected patients. STUDY DESIGN: Patients with HI/HA (8 children and 6 adults) were studied. All had dominantly expressed mutations of glutamate dehydrogenase and plasma concentrations of ammonium that were 2 to 5 times normal. The responses to a 24-hour fasting test were determined in 7 patients. Responses to a 1.5 gm/kg oral protein tolerance test in 12 patients were compared with responses of 5 control subjects. RESULTS: The median age at onset of hypoglycemia in the 14 patients was 9 months; diagnosis was delayed beyond age 2 years in 6 patients, and 4 were not given a diagnosis until adulthood. Fasting tests revealed unequivocal evidence of hyperinsulinism in only 1 of 7 patients. Three did not develop hypoglycemia until 12 to 24 hours of fasting; however, all 7 demonstrated inappropriate glycemic responses to glucagon that were characteristic of hyperinsulinism. In response to oral protein, all 12 patients with HI/HA showed a fall in blood glucose compared with none of 5 control subjects. Insulin responses to protein loading were similar in the patients with HI/HA and control subjects. CONCLUSION: The postprandial blood glucose response to a protein meal is more sensitive than prolonged fasting for detecting hypoglycemia in the HI/HA syndrome.
Assuntos
Proteínas Alimentares/efeitos adversos , Jejum/efeitos adversos , Hiperamonemia/fisiopatologia , Hiperinsulinismo/fisiopatologia , Hipoglicemia/etiologia , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Glutamato Desidrogenase/genética , Glutamato Desidrogenase/metabolismo , Humanos , Hiperamonemia/genética , Hiperinsulinismo/genética , Lactente , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , SíndromeRESUMO
OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the beta-cell adenosine triphosphate-dependent potassium channel complex and to distinguish focal and diffuse forms of hyperinsulinism caused by these mutations. STUDY DESIGN: The acute insulin response to intravenous calcium stimulation (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no symptoms, and 9 normal adults. Three infants with congenital focal disease, 1 with diffuse hyperinsulinism, and the child with insulinoma underwent selective pancreatic intra-arterial calcium stimulation with hepatic venous sampling. RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital focal hyperinsulinism responded to CaAIR, whereas the normal control group, patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did not. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling revealed selective, significant step-ups in insulin secretion that correlated anatomically with the location of solitary lesions confirmed surgically in 2 of 3 infants with congenital focal disease and in the child with insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic venous sampling demonstrated markedly elevated baseline insulin levels throughout the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The intravenous CaAIR is a safe and simple test for identifying infants with diffuse SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative selective arterial calcium stimulation of the pancreas with hepatic venous sampling can localize focal lesions causing hyperinsulinism in children. The combination of these calcium stimulation tests may help distinguish focal lesions suitable for cure by local surgical resection.
Assuntos
Transportadores de Cassetes de Ligação de ATP , Cálcio , Hiperinsulinismo/congênito , Hiperinsulinismo/diagnóstico , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio , Receptores de Droga , Compostos de Sulfonilureia/metabolismo , Adolescente , Adulto , Cálcio/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Feminino , Humanos , Hiperinsulinismo/sangue , Lactente , Injeções Intravenosas , Masculino , Canais de Potássio/genética , Receptores de Droga/genética , Receptores de SulfonilureiasRESUMO
OBJECTIVE: Serial Doppler ultrasonography and long-term neurodevelopmental follow-up outcomes were evaluated prospectively in neonates whose right common carotid artery (RCCA) was reconstructed after extracorporeal membrane oxygenation (ECMO). METHODS: Children with RCCA reconstruction (n = 34) were monitored for 3.5 to 4.5 years by Doppler ultrasonography for arterial patency, and 28 had IQ testing by 5 years. A comparison group consisted of 35 infants who had RCCA ligation after ECMO. Neonatal electroencephalograms and computed tomography/magnetic resonance imaging scans were also compared. RESULTS: Reconstructions were successful (<50% RCCA stenosis by Doppler ultrasonography) in 26 (76%) of 34 children, 3 (9%) had >/=50% stenosis, and 5 (15%) had occlusion. No significant differences were seen between reconstructed and ligated groups in neonatal complications or ECMO courses. Occurrence of marked neonatal electroencephalographic abnormalities did not differ between groups. Abnormalities on computed tomography/magnetic resonance imaging scans (4 of 31 vs 11 of 29, P =.025) and cerebral palsy (0 of 34 vs 5 of 35, P =.054) were more common in infants with RCCA ligation. No differences were seen in developmental or IQ scores between the 2 groups, and 4 in each group had cognitive handicaps (at least 1 IQ score <70). CONCLUSIONS: Most RCCA reconstructions remained patent, with 24% showing significant stenosis or occlusion. Compared with a historical control group, patients with RCCA reconstruction had fewer brain scan abnormalities and tended to be less likely to have cerebral palsy. RCCA reconstruction after venoarterial ECMO may improve outcome.
Assuntos
Artéria Carótida Primitiva/cirurgia , Oxigenação por Membrana Extracorpórea , Peso ao Nascer , Artéria Carótida Primitiva/diagnóstico por imagem , Eletroencefalografia , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Testes de Inteligência , Ligadura , Imageamento por Ressonância Magnética , Resultado do Tratamento , Ultrassonografia , Grau de Desobstrução VascularRESUMO
OBJECTIVE: The relationship between bronchopulmonary dysplasia (BPD) and neurodevelopmental outcome after extracorporeal membrane oxygenation (ECMO) has not been extensively reported. We compared the outcomes in a large series of infants with and without BPD after ECMO. STUDY DESIGN: Hospital charts and follow-up records of 145 infants treated with ECMO (1985 through 1990) were reviewed. Complete long-term respiratory and follow-up outcome data were available in 64 infants. BPD occurred in 17 survivors; the remaining 47 did not have BPD. RESULTS: Babies with BPD were more likely to have had respiratory distress syndrome. Mean (+/- SD) age at ECMO initiation was later for the BPD group (127+/-66 vs 53+/-39 hours, p < 0.001), and the duration of ECMO treatment was longer (192+/-68 vs 119+/-53 hours, p < 0.001). Bayley Scales of Infant Development scores at <30 months were lower in infants with BPD (p < 0.001), as were three of four Mullen Scales of Early Learning scores (> or = 30 months, p < 0.001 or p = 0.01). At 57+/-16 months 11 (64%) patients with BPD had mild neurologic disabilities, and 3 (18%) had severe disabilities. At a similar age (53+/-16 months, p = NS) 16 (34%) patients without BPD had mild disabilities, whereas 2 (4%) had severe disabilities (p < 0.01). CONCLUSIONS: The occurrence of BPD after ECMO is associated with adverse neurodevelopmental outcome. Patients with BPD after ECMO merit close long-term follow-up.
Assuntos
Displasia Broncopulmonar/terapia , Deficiências do Desenvolvimento/etiologia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Displasia Broncopulmonar/complicações , Feminino , Seguimentos , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Testes Neuropsicológicos , Síndrome do Desconforto Respiratório do Recém-Nascido/complicaçõesRESUMO
We describe three families with hypoglycemia caused by familial hyperinsulinism (HI) in whom vertical transmission of the disorder occurred, suggesting autosomal dominant (AD) inheritance. We therefore examined the relationship between the apparent AD disorder and the more common autosomal recessive (AR) form of HI, which has recently been linked to the sulfonylurea receptor on chromosome 11p15.1. The clinical features of the 11 patients with AD HI were milder than those seen in 14 patients with AR HI. Hypoglycemia was readily controlled with either diet alone or with diazoxide in 10 of 11 patients with AD HI but in none of those with the AR form. In one large pedigree, analysis of genomic DNA with polymorphic simple sequence repeat markers excluded linkage of AD HI to the SUR locus in a dominant manner. The possibility of linkage to the SUR locus could not be absolutely excluded in the two smaller pedigrees. None of the published mutations of the SUR gene identified in patients with AR HI were detected in the patients with the AD form. We conclude that the AD form of hyperinsulinism is phenotypically different from the AR variant. The identification of more families with this form of HI may make it possible to locate the responsible gene by the use of linkage analysis.