RESUMO
Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.
Assuntos
Centrômero , Cromossomos Humanos Par 10 , Doença de Hirschsprung/genética , Alelos , Mapeamento Cromossômico , Família , Feminino , Ligação Genética , Marcadores Genéticos , Genótipo , Humanos , Masculino , LinhagemRESUMO
Background: Shared decision-making at end of life (eol) requires discussions about goals of care and prioritization of length of life compared with quality of life. The purpose of the present study was to describe patient and oncologist discordance with respect to goals of care and to explore possible predictors of discordance. Methods: Patients with metastatic cancer and their oncologists completed an interview at study enrolment and every 3 months thereafter until the death of the patient or the end of the study period (15 months). All interviewees used a 100-point visual analog scale to represent their current goals of care, with quality of life (scored as 0) and survival (scored as 100) serving as anchors. Discordance was defined as an absolute difference between patient and oncologist goals of care of 40 points or more. Results: The study enrolled 378 patients and 11 oncologists. At baseline, 24% discordance was observed, and for patients who survived, discordance was 24% at their last interview. For patients who died, discordance was 28% at the last interview before death, with discordance having been 70% at enrolment. Dissatisfaction with eol care was reported by 23% of the caregivers for patients with discordance at baseline and by 8% of the caregivers for patients who had no discordance (p = 0.049; Ï = 0.20). Conclusions: The data indicate the presence of significant ongoing oncologist-patient discordance with respect to goals of care. Early use of a simple visual analog scale to assess goals of care can inform the oncologist about the patient's goals and lead to delivery of care that is aligned with patient goals.
Assuntos
Neoplasias , Oncologistas , Relações Médico-Paciente , Assistência Terminal , Adulto , Idoso , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Qualidade de VidaRESUMO
We examined now an ultraweak thermalized neutron field (UTNF) affects the structural transformation in DNA macromolecules at room temperature. IR-spectroscopy, electrophoresis, and filtration through nitrocellulose filter measurements revealed that UTNF irradiation with a fluence of F(n) - 1.0 - 3.7 x 10(7) n/cm2 (the absorbed dose as low as 10 - 50 microGy) can induce non negligible structural changes in DNA macromolecules in film as well as in an aqueous solution. These structural changes appear as a type of reversible conformational transition from the A-form to a disordered state, as well as through intermolecular cross-link formations and the generation of double-strand breaks.
Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , DNA Forma A/química , Nêutrons , Animais , Bovinos , Eletroforese , Camundongos , Conformação de Ácido Nucleico/efeitos da radiação , Espectrofotometria InfravermelhoRESUMO
Progressive systemic sclerosis (PSS) is associated with a broad spectrum of autoimmune thyroid diseases. While an association between PSS and hypothyroidism is well established, a relationship between PSS and hyperthyroidism is less well defined. We treated three patients with PSS whose course was complicated by Graves' disease. Because hyperthyroidism can simulate many of the symptoms of PSS progression and treatment of hyperthyroidism can lead to resolution of clinical deterioration in such patients, it is important to recognize the simultaneous occurrence of these diseases.
Assuntos
Doença de Graves/complicações , Escleroderma Sistêmico/complicações , Adulto , Diagnóstico Diferencial , Doença de Graves/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/diagnósticoRESUMO
Pregnant mice were exposed to a single dose of alcohol (0.03 ml of 25% alcohol X g-1 mouse) or two doses (2 X 0.015 ml of 25% alcohol X g-1 mouse) 4 h apart, by intraperitoneal injection or by gavage, on days 7, 8, 9 or 10 of gestation. The mice were killed on the day before term and the fetuses examined for heart defects. Alcohol exposure on day 8, 9 or 10 of gestation caused a high incidence of ventricular septal defects (60%, 75% and 15% respectively). Defects of both the membranous and muscular parts of the septum were seen as well as more complex ventricular septal defects involving the great vessels. Day 7 was resistant to the induction of heart defects. This study has demonstrated that a relatively short exposure to high doses of alcohol during pregnancy in mice can cause congenital heart defects. This has important implications both as a possible cause of congenital heart anomalies in humans and for the counselling of mothers of affected children.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Etanol/farmacologia , Coração Fetal/efeitos dos fármacos , Cardiopatias Congênitas/induzido quimicamente , Animais , Feminino , Idade Gestacional , Cardiopatias Congênitas/patologia , Comunicação Interventricular/induzido quimicamente , Camundongos , Miocárdio/patologia , Gravidez , Fatores de TempoRESUMO
Serum gastrin concentrations were measured in 22 untreated and 10 treated thyrotoxic patients. In contrast to similar studies carried out in Japan, serum gastrin levels were normal in hyperthyroid subjects. The mean value in hyperthyroid subjects (94.8 +/- 34.5 pg/ml) was higher than that in the treated patients (73.6 +/- 33.2 pg/ml), but the difference was not significant (P greater than 0.05).
Assuntos
Gastrinas/sangue , Hipertireoidismo/sangue , Adulto , Idoso , Feminino , Doença de Graves/sangue , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies have suggested that children with phenylketonuria (PKU) have a reduction in bone mineralization compared with control subjects. To investigate this, bone mineral density (BMD) of the total body (TBMD) was measured in 32 prepubertal children with PKU and in 95 age-matched control subjects. Spine bone mineral density (SBMD) was also recorded in a subset, 24 with PKU and 55 control subjects. The effect of dietary intake on bone mass was assessed in 30 of the children with PKU and in 12 control subjects. In the children with PKU, TBMD and SBMD were significantly lower than in the control subjects after adjustment for height and weight (P = 0.03 and P = 0.003, respectively). The children with PKU had a higher intake of calcium (P < 0.0001), phosphorus (P = -0.0002), and magnesium (P < 0.0001), suggesting that their lower BMD occurred despite an adequate diet based on current recommendations. Further study is needed to establish the cause of this deficit in bone mass and the benefit of additional nutritional support to reverse this problem.
Assuntos
Densidade Óssea , Fenilcetonúrias/fisiopatologia , Absorciometria de Fóton , Análise de Variância , Estatura , Criança , Dieta , Feminino , Humanos , Masculino , Fenilalanina/sangue , Análise de RegressãoAssuntos
Alumínio/química , Cristalização/métodos , Eletroquímica/métodos , Membranas Artificiais , Nanosferas/química , Nanosferas/ultraestrutura , Nanotecnologia/métodos , Eletrodos , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Fotografação/métodos , Porosidade , Propriedades de SuperfícieRESUMO
Spinal cord injury leads to acute local ischemia, which may contribute to secondary degeneration. Hypoxia stimulates angiogenesis through a cascade of events, involving angiogenesis stimulatory substances, such as vascular endothelial growth factor (VEGF). To test the importance of angiogenesis for functional outcome and wound healing in spinal cord injury VEGF165 (proangiogenic), Ringer's (control) or angiostatin (antiangiogenic) were delivered locally immediately after a contusion injury produced using the NYU impactor and a 25 mm weight-drop. Rats treated with VEGF showed significantly improved behavior up to 6 weeks after injury compared with control animals, while angiostatin treatment lead to no statistically significant changes in behavior outcome. Furthermore, VEGF-treated animals had an increased amount of spared tissue in the lesion center and a higher blood vessel density in parts of the wound area compared with controls. These effects were unlikely to be due to increased cell proliferation as determined by bromo-deoxy-uridine-labeling. Moreover, VEGF treatment led to decreased levels of apoptosis, as revealed by TUNEL assays. In situ hybridization demonstrated presence of mRNA for VEGF receptors Flt-1, fetal liver kinase-1, neuropilin-1 and -2 in several important cellular compartments of the spinal cord. The different experiments indicate that beneficial effects seen by acute VEGF delivery was attributable to protection/repair of blood vessels, decreased apoptosis and possibly also by other additional effects on glial cells or certain neuron populations.
Assuntos
Fatores de Crescimento Endotelial/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Linfocinas/uso terapêutico , Degeneração Neural/tratamento farmacológico , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Análise de Variância , Indutores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/administração & dosagem , Angiostatinas , Animais , Animais Recém-Nascidos , Antígenos/metabolismo , Astrócitos , Comportamento Animal/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Bromodesoxiuridina/farmacocinética , Contagem de Células , Morte Celular , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Indóis/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/genética , Linfocinas/metabolismo , Proteínas de Neurofilamentos/metabolismo , Neuropilina-1/genética , Neuropilina-2/genética , Fragmentos de Peptídeos/administração & dosagem , Plasminogênio/administração & dosagem , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Medula Espinal/citologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Total serum thyroxine (T4), triiodothyronine (T3), T3 resin uptake (T3U), thyrotrophin (TSH), and reverse T3 (rT3) were measured in 209 healthy adults 20--89 yr old. Mean T4 values for men were stable throughout life, but in females under age 60, T4 values were significantly higher than in older women. Values for T3U in males were significantly higher than in females throughout all decades, although females had a significant increase in T3U after age 60. TSH values increased significantly in females over age 60. Throughout all decades, males had stable TSH levels that were slightly higher than the female results before age 60 and lower thereafter. Mean serum T3 declined similarly for both sexes with increasing age, although not to the extent previously reported. Men had significantly higher mean rT3 values over all decades than females, although female rT3 levels decreased after age 50 whereas males maintained stable values. The physiologic reasons for these findings may be due to sex-related changes in binding proteins and alterations in metabolic clearance rates, production, and degradation of these hormones with increasing age.
Assuntos
Envelhecimento , Testes de Função Tireóidea , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
The Golli-mbp gene complex contains two overlapping transcription units with two distinct promoters, of which the downstream (myelin basic protein [mbp]) promoter is more frequently used. A previous comparison of the downstream promoter sequences from shark and mouse allowed the identification of two DNA sequences called the boxes I and II and the wobble zone. The boxes I and II sequence is a composite cis-acting motif that is thought to be involved in the regulation of the downstream promoter. It contains sequences similar to T-antigen, MyoD/E2A, and glucocorticoid receptor-binding sites. The wobble zone codes for an exon (5a in the nomenclature of Campagnoni et al., 1993) that is included in messenger RNAs transcribed from the upstream promoter. The polypeptides encoded by this exon from shark and mouse are 86 and 84 amino acids long, respectively. These polypeptides are overall 59% identical and include a region (residues 41-75 in shark and 39-73 in mouse) that is 89% identical between the two species. A primary sequence analysis showed that each of these polypeptides contains an N-glycosylation site, phosphorylation sites for Ca2+/calmodulin-dependent protein kinase, protein kinase C and casein kinase II, and partial ATP- and GTP-binding sites. The shark polypeptide also contains a phosphorylation site for proline-directed protein kinase. These observations are consistent with the notion that the intricate structure and regulation of the Golli-mbp gene complex arose during vertebrate evolution within a common ancestor to sharks and mammals.
Assuntos
Genes , Camundongos/genética , Proteína Básica da Mielina/genética , Tubarões/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fenômenos Químicos , Físico-Química , Éxons , Dados de Sequência Molecular , Proteína Básica da Mielina/química , Alinhamento de Sequência , Homologia de Sequência , Especificidade da EspécieRESUMO
Interview data for events of pregnancy on 40 infants with Hirschsprung disease showed a significant relationship to a history of hyperthermia in the mother in the first trimester, during the time of embryonic development and migration of ganglion cells along the intestine. In order to eliminate maternal recall bias, a control group consisted of 41 malformed infants with congenital limb deficiency. Hyperthermia may be one factor contributing to the cause of some cases of Hirschsprung disease.
Assuntos
Febre/complicações , Doença de Hirschsprung/etiologia , Complicações Infecciosas na Gravidez , Feminino , Idade Gestacional , Doença de Hirschsprung/embriologia , Doença de Hirschsprung/genética , Humanos , Lactente , Masculino , Troca Materno-Fetal , GravidezRESUMO
A male infant was born with symmetrical tetramelic limb deficiency consisting of bilateral upper limb amelia with severe symmetrical proximal focal femoral deficiency and fibula deficiency associated with left splenogonodal fusion of the discontinuous type, micrognathia, and a prominent capillary haemangioma of the face. The parents are first cousin Lebanese muslims. This observation suggests the possibility of recessive inheritance in some cases of the Amelia, Femur-Fibula dysostosis syndrome with or without splenogonadal fusion.
Assuntos
Anormalidades Múltiplas/genética , Ectromelia/genética , Baço/anormalidades , Testículo/anormalidades , Consanguinidade , Genes Recessivos , Hemangioma Capilar , Humanos , Recém-Nascido , Masculino , Micrognatismo/genética , Neoplasias NasaisRESUMO
We describe 2 patients with bilateral right-angle bowing of femora, absence of fibulae, and reduced, flattened and nail-less toes and symmetrical fingernail deficiency in a consanguineous family of ethnic South Vietnamese Baptists and a non-consanguineous Polish family. These cases are similar to those reported by Fuhrmann et al. (in "Skeletal Dysplasias," New York: Alan R. Liss, Inc., pp 519-524), indicating possible autosomal recessive inheritance of this rare non-lethal limb malformation syndrome.
Assuntos
Anormalidades Múltiplas/genética , Fêmur/anormalidades , Fíbula/anormalidades , Deformidades Congênitas do Pé/genética , Deformidades Congênitas da Mão/genética , Osso Púbico/anormalidades , Consanguinidade , Feminino , Genes Recessivos , Humanos , Recém-Nascido , Rim/anormalidades , Unhas MalformadasRESUMO
During the third week of pregnancy the human embryo undergoes a major developmental process, gastrulation, during which the two-layered embryo is converted into a three-layered embryo. At the same time, the upper epiblast layer is induced to form the neural plate. Evidence is presented which suggests that interference with this process by genetic, physical, or chemical agents can cause a range of CNS abnormalities and facial abnormalities, including those described as characteristic of the FAS.
Assuntos
Encéfalo/anormalidades , Ossos Faciais/anormalidades , Gástrula , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Encéfalo/embriologia , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Gravidez , Primeiro Trimestre da GravidezRESUMO
We present an infant who was exposed to warfarin throughout pregnancy and has warfarin embryopathy. When the child was examined radiologically at 20 months areas of calcification were visible in the septal and alar cartilages of the small external part of the nose. The location of this ectopic calcification is consistent with that seen in an animal model of the warfarin embryopathy. It supports the hypothesis that warfarin interferes with the prenatal growth of the cartilaginous nasal septum by inhibiting the normal formation of a vitamin K-dependent protein that prevents calcification of cartilage. The child also had severe abnormalities of the cervical vertebrae and secondary damage to the spinal cord. Cervical vertebral anomalies are a relatively common finding in the warfarin embryopathy and in the related Binder syndrome.
Assuntos
Calcinose/induzido quimicamente , Septo Nasal , Efeitos Tardios da Exposição Pré-Natal , Doenças da Medula Espinal/induzido quimicamente , Varfarina/efeitos adversos , Adolescente , Deficiência de Antitrombina III , Calcinose/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/efeitos dos fármacos , Vértebras Cervicais/patologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Septo Nasal/diagnóstico por imagem , Septo Nasal/efeitos dos fármacos , Septo Nasal/patologia , Gravidez , Radiografia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/patologiaRESUMO
We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion.
Assuntos
Anormalidades Múltiplas/genética , Aberrações Cromossômicas , Transtornos Cromossômicos , Cromossomos Humanos Par 10 , Síndrome de DiGeorge/genética , Orelha/anormalidades , Face/anormalidades , Feminino , Deleção de Genes , Humanos , Lactente , FenótipoRESUMO
Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.
Assuntos
Anormalidades Induzidas por Medicamentos , Anticonvulsivantes/efeitos adversos , Condrodisplasia Punctata/induzido quimicamente , Face/anormalidades , Fenitoína/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal , Vitamina K/administração & dosagem , Adulto , Criança , Condrodisplasia Punctata/prevenção & controle , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Vitamina K/uso terapêutico , Deficiência de Vitamina K/induzido quimicamente , Deficiência de Vitamina K/prevenção & controleRESUMO
A study was undertaken in paediatric patients suffering from ulcerative, Crohn's or indeterminate colitis. This aimed to compare the occurrence and tolerance of side-effects arising during treatment with position-release mesalazine (Asacol) with those occurring during previous treatment with sulphasalazine (Salazopyrin). The drugs were used to maintain remission from colitis. The occurrence of adverse reactions was also monitored. Sixty-seven children were assessed for a period of 6 months; 45 of these children received mesalazine after previous treatment with sulphasalazine. The results show that the majority of patients were maintained in remission with either drug, but they reported a preference for position-release mesalazine with respect to ease and frequency of administration when compared to sulphasalazine. No serious adverse reactions arose during mesalazine treatment, compared with three such events during previous sulphasalazine treatment.
Assuntos
Ácidos Aminossalicílicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Adolescente , Ácidos Aminossalicílicos/administração & dosagem , Ácidos Aminossalicílicos/efeitos adversos , Criança , Pré-Escolar , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Masculino , Mesalamina , Sulfassalazina/uso terapêuticoRESUMO
According to cognitive-experiential self-theory (CEST), individuals have 2 systems for processing information, a rational system and an experiential system. Research conducted under norm theory (NT) has provided impressive evidence of an if only (IO) effect associated with postoutcome processing of aversive events that are highly consistent with formulations in CEST. Two studies involving vignettes adapted from NT were conducted that tested 4 hypotheses and corollaries derived from CEST. It was demonstrated, in support of hypotheses, that the IO effect can be obtained with ratings of one's own and of a protagonist's specific behaviors, as well as with ratings of a protagonist's diffuse emotions (the usual procedure); that a rational orientation decreases the IO effect; that increasing the intensity of outcomes increases it; and that priming the experiential system reduces people's ability to subsequently think rationally. The theoretical and research implications of these findings are discussed.