RESUMO
BACKGROUND: Recurrent Clostridium difficile infection is a growing problem among children due to both the increasing survival of medically fragile children with complicated chronic medical conditions resulting in prolonged antibiotic exposure and hospitalization and the emergence of strains of Clostridium difficile that are hypervirulent and associated with high rates of relapse. CASE PRESENTATION: This case describes a medically complex 21-month-old Hispanic girl with Pompe disease and B cell immunodeficiency with recurrent Clostridium difficile infection refractory to antimicrobial management. She presented with nine recurrent episodes of Clostridium difficile infection including fever, foul smelling diarrhea, and respiratory distress with failed sustained responses to compliant treatment using metronidazole and pulsed vancomycin therapy. Maternal donor fecal microbiota transplantation was performed with complete symptom resolution and produced a sustained cure, now 5 years in duration. CONCLUSIONS: This patient presented with symptomatic Clostridium difficile at an early age causing significant morbidity and reduced quality of life. After nearly one year of failed medical management, fecal microbiota transplantation provided a cure. Further evidence-based research is necessary to test the safety and efficacy of this low technology, low cost, and morbidity-sparing therapy in children.
Assuntos
Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal/métodos , Doença de Depósito de Glicogênio Tipo II/complicações , Antibacterianos/administração & dosagem , Clostridioides difficile/isolamento & purificação , Diarreia/terapia , Enterocolite Pseudomembranosa/diagnóstico , Feminino , Humanos , Imunocompetência , Lactente , Metronidazol/administração & dosagem , Reação em Cadeia da Polimerase , Resultado do Tratamento , Vancomicina/administração & dosagemRESUMO
Consumers are concerned with fat consumption from meat products, and the ability to determine fat has changed with recent technological advances. The objective of this study was to predict fat percentage within marbling scores and compare 3 fat analysis procedures. Steaks (n = 119) were selected by USDA grading system using an E + V Vision Grading camera at a commercial beef plant during 1 d. Two samples per carcass were cut from the 13th rib, both sides, and transported to the University of Missouri meat laboratory. The sample from the right side of the carcass was allotted to Warner-Bratzler shear force, and the sample from the left side, which was graded by the camera, was allotted to fat extraction. Warner-Bratzler shear force samples were cut into 2.54-cm steaks and aged for 14 d. Steaks allotted to fat extraction were trimmed of all external fat and twice ground using 8- and 4-mm grinding plates. The finely ground beef was then split into its allotted fat-extraction methods. The 3 methods used in fat extraction were 2:1 chloroform/methanol (Folch), ether-extractable fat (ether), and microwave drying and nuclear magnetic resonance (CEM). Warner-Bratzler shear force values were not different between marbling scores (P > 0.05). Regardless of fat extraction method, fat percentage increased as marbling score increased (P < 0.05). All regression equations for fat percentage, regardless of extraction method, were linear. Prediction equation for fat percentage using CEM was -3.46 + 0.016 (marbling score), R(2) of 0.824 (P < 0.0001). Prediction equation for fat percentage using ether was -3.08 + 0.017 (marbling score), R(2) of 0.859 (P < 0.0001). Prediction equation for fat percentage using Folch was -3.42 + 0.019 (marbling score), R(2) of 0.816 (P < 0.0001). When the CEM, Folch, and ether methods were compared, CEM and Folch regression lines had different slopes (P < 0.05). The slope of the regression line for ether was not different (P > 0.05) from CEM or Folch. Overall, ether is the most accurate method based on the R(2) value, but CEM is environmentally safe and the fastest method for determining total crude fat percentage.
Assuntos
Gorduras/análise , Indústria de Embalagem de Carne/métodos , Carne/análise , Animais , Composição Corporal , Bovinos , Processamento de Imagem Assistida por Computador , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: Central nervous system haemangioblastoma (HAB) is a major feature of von Hippel-Lindau (VHL) disease, and it is estimated that about 30% of HAB patients have VHL disease. Consequently, it is widely recommended that sporadic HAB patients are screened for clinical and radiological features of VHL disease because of the risk of multiple tumours. We investigated the frequency of VHL germline mutations in patients with HAB only with no clinical or radiological evidence of VHL disease to define the role of molecular genetic analysis in the management of such patients. METHODS: Eighty four patients with a single HAB (23 Dutch, 61 UK) and four with multiple HAB (two Dutch, two UK) were studied by direct sequencing of the coding region and quantitative Southern blotting. RESULTS: A VHL germline mutation was found in three of 69 (4.3%) single HAB patients aged 50 years or less (three of 84 (3.6%) total single HAB patients). A germline VHL mutation was detected in a 44 year old woman with a solitary cerebellar HAB, as well as in four clinically unaffected close relatives, and in two single HAB cases presenting at the ages of 29 and 36 years. Germline VHL mutations were detected in two of four cases with multiple HAB. CONCLUSIONS: Early detection of VHL disease is important to reduce morbidity and mortality and therefore we recommend that, in addition to conventional clinical and radiological investigations, VHL gene mutation analysis should be offered to all HAB patients younger than 50 years. HAB patients aged >50 years will have a lower a priori risk of VHL disease and further data are required to evaluate the role of routine molecular genetic investigations in late onset HAB cases. The failure to detect germline VHL mutations in some patients with multiple HAB may indicate the presence of somatic mosaicism or additional HAB susceptibility genes.
Assuntos
Neoplasias do Sistema Nervoso Central/genética , Mutação em Linhagem Germinativa/genética , Hemangioblastoma/genética , Doença de von Hippel-Lindau/genética , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Diagnóstico Diferencial , Feminino , Frequência do Gene , Hemangioblastoma/diagnóstico , Hemangioblastoma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Linhagem , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/epidemiologiaRESUMO
We report the ultrasound detection of cranial abnormalities at 14 weeks' gestation in a fetus subsequently confirmed as having tuberous sclerosis using DNA linkage analysis within the affected family. The presence of asymmetrical ventricular enlargement persisted antenatally. Magnetic resonance imaging at 26 weeks indicated the possibility of poor gyral formation consistent with a neuronal migration disorder. Cardiac rhabdomyomata were not visualized on ultrasound scan until 30 weeks' gestation. Postnatal cranial ultrasound confirmed the significant neuropathology which was manifested by severe developmental delay and intractable fits in the child. The potential benefits of earlier diagnosis of tuberous sclerosis by cranial imaging are discussed, although in this patient the routine booking scan resulted in a path of prenatal diagnosis being undertaken which had originally been declined. A mechanism is proposed to explain the variable expression of tuberous sclerosis within this family based on altered TSC2 activity affecting neuronal migration.
Assuntos
Doenças Fetais/diagnóstico , Ligação Genética , Diagnóstico Pré-Natal/métodos , Esclerose Tuberosa/diagnóstico , Adulto , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Linhagem , Gravidez , Primeiro Trimestre da Gravidez , Esclerose Tuberosa/diagnóstico por imagem , UltrassonografiaAssuntos
Doença de Alzheimer/genética , alfa-Macroglobulinas/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Autopsia , Inglaterra/epidemiologia , Frequência do Gene , Humanos , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo GenéticoRESUMO
The homozygous oim/oim mouse, a model of moderate-to-severe human osteogenesis imperfecta, contains a G-nucleotide deletion in the Cola-2 gene (the murine pro alpha(I) collagen gene) that results in accumulation of alpha1(I) homotrimer collagen. Although these mice have a distinctive phenotype that includes multiple fractures and deformities, genotyping is necessary to distinguish them from their wildtype (+/+) and heterozygote (oim/+) littermates. In this study, the dye primer and dye terminator chemistry methods, in combination with automated direct DNA sequencing, were compared for accuracy and ease in genotyping. A total of 82 mice from 14 litters were bred and genotyped; this resulted in 18 +/+, 35 oim/+, and 29 oim/oim mice. The dye primer and dye terminator chemistry methods worked equally well for identification of the deletion mutation and thus the genotype of all of the mice. However, the dye terminator method was found to be superior on the basis of the reduced amount of sample handling and reduced quantity of reagent required.
Assuntos
Colágeno/genética , Mutação , Osteogênese Imperfeita/genética , Análise de Sequência de DNA , Animais , Corantes , Genótipo , Camundongos , Reação em Cadeia da PolimeraseRESUMO
We report on a myotonic dystrophy (DM) family exhibiting instability of normal sized (CTG)n alleles in the DM kinase gene on the non-DM chromosome. At least two mutational events involving normal DM alleles must have occurred in this family; one was characterised as a 34-35 (CTG)n repeat mutation. These findings represent a dissociation between (CTG)n repeat instability and myotonic dystrophy. Furthermore, this family highlights genetic counselling issues relating to the pathogenicity of alleles at the upper end of the normal size range and the risk of further expansion into the disease range.
Assuntos
Alelos , Distrofia Miotônica/genética , Proteínas Serina-Treonina Quinases/genética , Repetições de Trinucleotídeos , Adulto , Feminino , Humanos , Masculino , Miotonina Proteína Quinase , LinhagemRESUMO
The expansion of a tandemly repeated trinucleotide sequence, CAG, is the mutational mechanism for several human genetic diseases. We present a generally applicable PCR amplification method using a fluorescently labelled locus specific primer flanking the CAG repeat together with paired primers amplifying from multiple priming sites within the CAG repeat. Triplet repeat primed PCR (TP PCR) gives a characteristic ladder on the fluorescence trace enabling the rapid identification of large pathogenetic CAG repeats that cannot be amplified using flanking primers. We used our method to test a cohort of 183 people from myotonic dystrophy families including unaffected subjects and spouses. Eighty five clinically affected subjects with expanded alleles on Southern blot analysis were all correctly identified by TP PCR. This method is applicable for any human diseases involving CAG repeat expansions.
Assuntos
DNA/análise , Distrofia Miotônica/genética , Reação em Cadeia da Polimerase/métodos , Repetições de Trinucleotídeos , Criança , Estudos de Coortes , Primers do DNA , Fluorescência , HumanosRESUMO
The first formal immunisation schedule for the delivery of triple (DTP) vaccine was drawn up in November 1960. Since 1960 there have been many changes to the immunisation schedule, with a further change proposed for 1996. These changes have been in response to new vaccine development and better understanding of vaccine immunology. Further changes are certain.
Assuntos
Esquemas de Imunização , Vacinação/história , História do Século XX , Humanos , Nova Zelândia , Vacinas/administração & dosagemRESUMO
The folate-sensitive fragile site FRAXE is located in proximal Xq28 of the human X chromosome and lies approximately 600 kb distal to the fragile X syndrome (FRAXA) fragile site at Xq27.3. The cytogenetic expression of FRAXE is thought to be associated with mental handicap, but this is usually mild compared to that of the more common fragile X syndrome that is associated with the expression of the FRAXA fragile site. The exact incidence of FRAXE mental retardation is uncertain. We describe here the results of a U.K. survey designed to assess the frequency of FRAXE in a population of individuals referred for fragile X syndrome testing and found to be negative for expansion events at the FRAXA locus. No FRAXE expansion events were found in 362 cytogenetically negative males studied, and one expansion event was identified in a sample of 534 males for whom cytogenetic analyses were either unrecorded or not performed. Further FRAXE expansion events were detected in two related females known to be cytogenetically positive for a fragile site in Xq27.3-28. To gain insight into the FRAXE phenotype, the clinical details of the identified FRAXE male plus three other FRAXE individuals identified through previous referrals for fragile X syndrome testing are presented. For the population studied, we conclude that FRAXE mental retardation is a relatively rare but significant form of mental retardation for which genetic diagnosis would be appropriate.
Assuntos
Síndrome do Cromossomo X Frágil/epidemiologia , Deficiência Intelectual/genética , Cromossomo X , Sequência de Bases , Sítios Frágeis do Cromossomo , Fragilidade Cromossômica , Inglaterra , Feminino , Síndrome do Cromossomo X Frágil/genética , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Dados de Sequência MolecularRESUMO
The recent return of the director-generalship of health to the medical domain raises some interesting historical questions about credentials, status and influence of this position over the past 75 years. This article examines three specific aspects - attempts since 1920 to introduce a nonmedical head, criteria for selection and changing patterns of tenure.
Assuntos
Administração em Saúde Pública , Pessoal Administrativo/história , História do Século XX , Humanos , Nova Zelândia , Administração em Saúde Pública/históriaRESUMO
We examined the eustachian valve and the limbus of the foramen ovale in 42 hearts with hypoplastic left heart syndrome (HLHS) and in 16 normal hearts. In HLHS, only 4.8% of the eustachian valves were moderately to well developed, whereas the remaining 95.2% were abnormal (p < 0.001): 92.9% of the eustachian valves were absent or markedly hypoplastic, and 2.4% had an abnormally redundant and enlarged eustachian valve. The eustachian valve was well developed in 87.5% of normal hearts. In addition, the lesser development of the eustachian valve seemed to correlate with lesser development of the left side of the heart. The limbus was well developed in 100% of the normal hearts and moderately to well developed in only 33.3% of the HLHS group (p < 0.001). Most hearts in the HLHS group had marked hypoplasia of the limbus, which was rotated and deviated so as to be close to the superior vena caval entrance.
Assuntos
Defeitos dos Septos Cardíacos/patologia , Síndrome do Coração Esquerdo Hipoplásico/patologia , Veia Cava Inferior/anormalidades , Valva Aórtica/anormalidades , Valva Aórtica/patologia , Estenose da Valva Aórtica/congênito , Estenose da Valva Aórtica/patologia , Distribuição de Qui-Quadrado , Humanos , Recém-Nascido , Valva Mitral/anormalidades , Valva Mitral/patologia , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/patologia , Distribuição Aleatória , Veia Cava Inferior/patologiaRESUMO
It has been reported that up to half of renal stones and associated urine specimens have been positive on culture, and that up to 50% of such stones contain magnesium ammonium phosphate. In a prospective study using infrared and wet chemical analysis, we found positive cultures in only 7 of 132 renal, 5 of 105 ureteral and 6 of 21 bladder stones obtained surgically and handled with sterility. Of the culture positive calculi only 43% from the kidney, none from the ureter and 50% from the bladder contained detectable magnesium ammonium phosphate. However, magnesium ammonium phosphate was detectable in 20% of renal, 2% of ureteral and 27% of bladder stones with negative cultures. Of the culture positive renal and ureteral calculi 42% were predominantly calcium phosphate and 17% were predominantly calcium oxalate. For culture negative stones 25% and 51% from the kidney, and 15% and 82% from the ureter were composed of predominantly calcium phosphate and calcium oxalate, respectively. Among the culture positive stones, related positive urine cultures were noted in 100% of the renal, 20% of the ureteral and 50% of the bladder cases, compared to 26%, 10% and 27%, respectively, of culture negative calculi. The same organism was found in the stone and urine in only 38% of the cases. The lower frequency of positive urine cultures, of stones with magnesium ammonium phosphate, and especially of culture positive renal and ureteral stones (5%) than in previous reports suggests that stone culture may be of less value than indicated previously, except for bladder calculi and large renal stones, such as the branched type.
Assuntos
Bactérias/isolamento & purificação , Cálculos Urinários/microbiologia , Adulto , Idoso , Oxalato de Cálcio/análise , Fosfatos de Cálcio/análise , Feminino , Humanos , Compostos de Magnésio/análise , Masculino , Pessoa de Meia-Idade , Fosfatos/análise , Estudos Prospectivos , Estruvita , Cálculos Urinários/químicaRESUMO
cDNA clones from a human adult testis cDNA library were isolated and sequenced as part of a programme to produce expressed sequence tags (ESTs). ESTs were used routinely to search DNA and protein sequence databases. One clone (142) showed 60% identity to the Bacillus subtilis glycerol kinase gene at both the DNA and amino acid sequence levels. Analysis of DNA from somatic cell hybrids carrying deleted X chromosomes, has shown that clone 142 detects homologous sequences between Xp21.2-p22.1 (the interval containing the locus responsible for glycerol kinase deficiency--GKD). These sequences are deleted in two patients with GKD. Clone 142 also detects homologous sequences on Xq and at several autosomal loci. The sequences of clone 142 and two further cDNA clones isolated from a human foetal brain cDNA library are presented.
Assuntos
Bacillus subtilis/genética , Proteínas de Bactérias/genética , Clonagem Molecular/métodos , Glicerol Quinase/genética , Homologia de Sequência , Sitios de Sequências Rotuladas , Cromossomo X , Sequência de Aminoácidos , Animais , Sequência de Bases , Encéfalo , Mapeamento Cromossômico , Cosmídeos , DNA/genética , Glicerol Quinase/deficiência , Humanos , Células Híbridas , Hibridização in Situ Fluorescente , Masculino , Camundongos , Dados de Sequência Molecular , Alinhamento de Sequência , TestículoRESUMO
Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.
Assuntos
Oxalato de Cálcio/análise , Fosfatos de Cálcio/análise , Cálculos Renais/química , Acidose Tubular Renal/sangue , Acidose Tubular Renal/urina , Ácidos/metabolismo , Cloreto de Amônio/farmacologia , Bicarbonatos/farmacologia , Ritmo Circadiano , Proteínas Alimentares/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Rim/diagnóstico por imagem , Masculino , Fosfatos/sangue , Radiografia , Fatores de Risco , Albumina Sérica/análise , TomografiaRESUMO
John Knox Stuart of Glasgow epitomises the kind of 19th-century medical entrepreneur whose activities were intended to be curbed by the 1858 Medical Act. Druggist, obstetrician, builder, lecturer, poet and philanderer, his career was a chequered and eventful one.