Whole-exome sequencing for RH genotyping and alloimmunization risk in children with sickle cell anemia.

RH genes are highly polymorphic and encode the most complex of the 35 human blood group systems. This genetic diversity contributes to Rh alloimmunization in patients with sickle cell anemia (SCA) and is not avoided by serologic Rh-matched red cell transfusions. Standard serologic testing does not distinguish variant Rh antigens. Single nucleotide polymorphism (SNP)-based DNA arrays detect many RHD and RHCE variants, but the number of alleles tested is limited. We explored a next-generation sequencing (NGS) approach using whole-exome sequencing (WES) in 27 Rh alloimmunized and 27 matched non-alloimmunized patients with SCA who received chronic red cell transfusions and were enrolled in a multicenter study. We demonstrate that WES provides a comprehensive RH genotype, identifies SNPs not interrogated by DNA array, and accurately determines RHD zygosity. Among this multicenter cohort, we demonstrate an association between an altered RH genotype and Rh alloimmunization: 52% of Rh immunized vs 19% of non-immunized patients expressed variant Rh without co-expression of the conventional protein. Our findings suggest that RH allele variation in patients with SCA is clinically relevant, and NGS technology can offer a comprehensive alternative to targeted SNP-based testing. This is particularly relevant as NGS data becomes more widely available and could provide the means for reducing Rh alloimmunization in children with SCA.

Anaerobic digestion and co-digestion processes of vegetable and fruit residues: process and microbial ecology.

This study evaluated the feasibility of methane production from fruit and vegetable waste (FVW) obtained from the central food distribution market in Mexico City using an anaerobic digestion (AD) process. Batch systems showed that pH control and nitrogen addition had significant effects on biogas production, methane yield, and volatile solids (VS) removal from the FVW (0.42 m(biogas)(3)/kg VS, 50%, and 80%, respectively). Co-digestion of the FVW with meat residues (MR) enhanced the process performance and was also evaluated in a 30 L AD system. When the system reached stable operation, its methane yield was 0.25 (m(3)/kg TS), and the removal of the organic matter measured as the total chemical demand (tCOD) was 65%. The microbial population (general Bacteria and Archaea) in the 30 L system was also determined and characterized and was closely correlated with its potential function in the AD system.

Allergic gastroenteropathy in preterm infants.

OBJECTIVES: To determine the clinical presentation, histopathologic features, and outcome of biopsy-proven allergic gastroenteropathy (AGE) in preterm infants. We hypothesized that AGE is a more frequent cause of gastrointestinal disease in this population than previously suspected. STUDY DESIGN: The retrospective portion of the study, from 1992 to 1997, included preterm infants <37 weeks' gestation who underwent biopsy because of suspected AGE. The prospective portion, from January to December 1998, included 20 infants undergoing endoscopy and biopsy because of suspected AGE. RESULTS: Twenty-five infants (12 retrospective/13 prospective) with mean gestational age of 29 weeks at birth and mean postnatal age at diagnosis of 78 days were diagnosed with AGE. Three clinical patterns of presentation were noted: group 1, gastroesophageal reflux disease (n = 5); group 2, non-specific feeding intolerance (n = 8); and group 3, lower gastrointestinal bleeding (n = 12). Ten patients had negative biopsy findings (3 retrospective/7 prospective) and had clinical features indistinguishable from those of groups 1 and 2. Patients in group 3 were most likely to have positive biopsy findings (12 of 12). Fifteen patients responded to a casein hydrolysate formula, and 10 patients required an amino acid-based formula. Patients with AGE who had eosinophilic infiltration and villous atrophy took longer to recover than those with eosinophilic infiltration alone (P <.03). Subsequently, most have tolerated formula challenges and are currently tolerating cow's milk. CONCLUSIONS: AGE may be an under-recognized cause of gastrointestinal symptoms in preterm infants. Confirmation with endoscopy and biopsy can be done safely and provides the basis for appropriate dietary management.

Oral health and denture quality: a pilot study in Trinidad

OBJECTIVE: To assess the quality of dentures worn by a sample of the population in Trinidad and respondents' attitude towards their oral health and dentures. DESIGN AND METHODS: Respondents to advertisements in all the local newspapers for persons wearing full dentures were interviewed and examined clinically. Dentures were examined for processing defects. Mandibular functional movements were measured and dentures were evaluated for reproduction of these movements. RESULTS: In the 54 subjects studied none of the dentures were made to function with mandibular jaw movements. For the maxilla and mandibular dentures, 96.8 percent of the axial inclination of the teeth were set incorrectly. All of the denture extensions were found to be short and none had any retention or stability. None of the participants had post delivery visits. The majority (77.5 percent) of all the dentures had never been repaired and 61.3 percent had fractured teeth. A majority (51.6 percent) of participants were found to be in need of palliative treatment and 48.4 percent needed urgent treatment. The primary concerns of the participants were that they were slack (35.5 percent). The majority of dentures sampled (80.6 percent) were made by a dental technician who also did the clinical procedures. CONCLUSIONS: The dentures made in Trinidad fall below acceptable standards and majority were made without any relation to functional jaw movements. However, patients' compliance with their prostheses was high (75 percent). There is an urgent need to a concerted effort by health officials to standardize oral health care.(AU)

Uleine and demethoxyaspidospermine from the bark of Plumeria lancifolia.

The isolation of (+)-uleine (1) and (+)-demethoxyaspidospermine (2) from the bark of Plumeria lancifolia is reported along with (1)H- and (13)C-NMR data.

Bioassay of thyrotropin receptor antibodies with Chinese hamster ovary cells transfected with recombinant human thyrotropin receptor: clinical utility in children and adolescents with Graves disease.

OBJECTIVE: The objective of this study was to compare the clinical utility of a new bioassay for thyrotropin (TSH) receptor antibodies (Abs) with the conventional radioreceptor assay and with measurement of thyroid peroxidase Abs in the diagnosis of Graves disease in childhood. STUDY DESIGN: Serum samples obtained from 22 children and adolescents with Graves disease (19 hyperthyroid, 3 in remission), 13 children and adolescents with chronic lymphocytic thyroiditis, and 17 normal children in a control group were evaluated. RESULTS: TSH receptor Abs were detected by bioassay in 10 (91%) of 11 patients with active Graves disease but in 0 of 2 patients in remission, 0 of 13 normal members of the control group, and 0 of 11 patients with chronic lymphocytic thyroiditis including 1 with thyrotoxicosis. The sensitivity and specificity of TSH receptor Abs detected by radioreceptor assay studied in the same 11 patients and in an additional 11 patients was similar to bioassay. In contrast, thyroid peroxidase Abs were detected in only 12 (71%) of 17 patients with Graves disease but in 11 of 11 patients with chronic lymphocytic thyroiditis and in 0 of 17 members of the control group. CONCLUSION: Bioassay of TSH receptor Abs is both sensitive and specific for the diagnosis of active Graves disease in the young. When cost and simplicity are considered, however, bioassay offers no advantage over radioreceptor assay for initial diagnostic screening. Rather, bioassay for TSH receptor Abs may be useful in thyrotoxic patients who are negative initially in the radioreceptor assay or in treated patients whose clinical picture is discordant with results in the radioreceptor assay.

Successful treatment of massive acute thyroid hormone poisoning with iopanoic acid.

We report a toddler with massive thyroid hormone poisoning in whom the addition of iopanoic acid to the treatment regimen (propylthiouracil and propranolol) resulted in a dramatic clinical and biochemical improvement. Iopanoic acid is a safe and effective drug in the treatment of massive thyroid hormone poisoning in children.

Genetic differentiation between and within strains of the saw-toothed grain beetle, Oryzaephilus surinamensis (Coleoptera: Silvanidae) at RAPD loci.

Nine strains of Oryzaephilus surinamensis have been kept in laboratory culture for periods ranging from 5 to 30 years (30-180 generations). Two RAPD primers provided sufficient information to separate the strains reliably and unambiguously. The strains are maintained at a population size of 200 breeding adults. The marked divergence between strains is consistent with the small population size, which for the older strains, according to population genetics theory, implies that roughly half the original genetic variation should now be lost from within strains. However, there is no indication that the older strains have less inter-strain variation. The results demonstrate RAPD loci can reliably detect population subdivision, which in field populations of pest species is of fundamental importance in understanding the population genetics of insecticide resistance.

Cirugia pediatrica ambulatoria: el desarrollo de un centro de Hospital de Dia / Ambulatory Pediatric Surgery: the development of a Day Care surgical center

La cirugia ambulatoria se ha transformado en un importante componente dentro de la pra ctica quirurgica. En 1987 se crea una unidad de Hospital de Dia en el Hospital de Niños de la Cruz Roja en Sudafrica. Evaluamos la experiencia acumulada en un periodo de 8 años (1987-1994) y la relacionamos con la cantidad total de intervenciones quirurgicas, la preparacion preoperatoria, utilizacion diaria de las instalaciones y cuidados postoperatorios junto con las complicaciones. En ese periodo se operaron 20.545 pacientes con una edad promedio de 3 anos. Participaron 9 sub-especialidades. El asesoramiento y la preparacion prequirurgica redujeron el porcentaje de suspension el dia de la cirugia a menos del 6 por ciento con un uso efectivo de las horas programadas de quirofano del 90 por ciento. Los escasos recursos humanos de enfermeria fueron tambien optimizados (relacion Paciente/Enfermera=11/1). El seguimiento postoperatorio de todos los procedimientos inguino-escrotales arrojo un porcentaje de complicaciones menor al 4 por ciento. La mayor parte de los procedimientos se efectuaron en menos de 30 minutos y solo el 0,8 por ciento excedio 1 hora de tiempo quirurgico. El promedio de tiempo de internacion fue de 6 horas. No se presentaron mayores complicaciones y la aceptacion por parte de los padres y los pacientes fue excelente. Solo 16 niños requirieron hospitalizacion prolongada durante la noche. Presentamos recomendaciones para establecer y mejorar los servicios del Hospital de Dia. Se puede concluir que las comunidades y las autoridades de los paises en vias de desarrollo pueden establecer un servicio de Hospital de Dia efectivo practico y eficiente, con bajos costos, expendiendo las instalaciones para la practica de cirugia ambulatoria

Cirugia pediatrica ambulatoria: el desarrollo de un centro de Hospital de Dia / Ambulatory Pediatric Surgery: the development of a Day Care surgical center

La cirugia ambulatoria se ha transformado en un importante componente dentro de la pra ctica quirurgica. En 1987 se crea una unidad de Hospital de Dia en el Hospital de Niños de la Cruz Roja en Sudafrica. Evaluamos la experiencia acumulada en un periodo de 8 años (1987-1994) y la relacionamos con la cantidad total de intervenciones quirurgicas, la preparacion preoperatoria, utilizacion diaria de las instalaciones y cuidados postoperatorios junto con las complicaciones. En ese periodo se operaron 20.545 pacientes con una edad promedio de 3 anos. Participaron 9 sub-especialidades. El asesoramiento y la preparacion prequirurgica redujeron el porcentaje de suspension el dia de la cirugia a menos del 6 por ciento con un uso efectivo de las horas programadas de quirofano del 90 por ciento. Los escasos recursos humanos de enfermeria fueron tambien optimizados (relacion Paciente/Enfermera=11/1). El seguimiento postoperatorio de todos los procedimientos inguino-escrotales arrojo un porcentaje de complicaciones menor al 4 por ciento. La mayor parte de los procedimientos se efectuaron en menos de 30 minutos y solo el 0,8 por ciento excedio 1 hora de tiempo quirurgico. El promedio de tiempo de internacion fue de 6 horas. No se presentaron mayores complicaciones y la aceptacion por parte de los padres y los pacientes fue excelente. Solo 16 niños requirieron hospitalizacion prolongada durante la noche. Presentamos recomendaciones para establecer y mejorar los servicios del Hospital de Dia. Se puede concluir que las comunidades y las autoridades de los paises en vias de desarrollo pueden establecer un servicio de Hospital de Dia efectivo practico y eficiente, con bajos costos, expendiendo las instalaciones para la practica de cirugia ambulatoria

Outcome in three siblings with antibody-mediated transient congenital hypothyroidism.

A woman receiving thyroxine substitution therapy for acquired hypothyroidism caused by autoimmune thyroiditis gave birth to three babies who had transient primary hypothyroidism. All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values. Thyrotropin receptor-blocking antibodies were present in maternal serum and in the three neonates. Each baby also had a different congenital malformation. The neurodevelopmental outcome of the children appeared related in part to maternal thyroxine levels, which suggests that transplacental transfer of thyroxine may protect the fetal brain.

Symptomatic non-insulin-dependent diabetes mellitus during therapy with recombinant human growth hormone.

In a 12-year-old girl, hyperglycemia and an elevated glycohemoglobin concentration developed after therapy with growth hormone for familial short stature. Both clinical and biochemical abnormalities disappeared after therapy was discontinued. The insulin response to an oral glucose tolerance test was abnormal 3 months after discontinuation of growth hormone; 18 months later, it remained delayed but was normal quantitatively.

Duplex scanning of the inferior epigastric artery.

PURPOSE: The inferior epigastric artery (IEGA) has been used as a conduit for coronary artery bypass grafting. Because of varying lengths, diameters, and depths, a method of determining vessel adequacy before operation was needed. METHOD: A BioSound Phase II scanner (BioSound, Indianapolis, Ind.) with a 10 MHz probe was used to image the IEGA in 40 patients. Beginning at the common femoral artery and moving superiorly, the external iliac artery is identified with its first branch, which is the IEGA. The IEGA is located deep in the rectus muscle, along the posterior rectus sheath. Frequent measurements of the diameter and depth are taken along the length of the IEGA. RESULTS: When comparing the group of patients in whom there was operative confirmation of the ultrasound findings, we found, on the right side, a mean length of 9.0 cm and mean diameter of 2.4 mm by ultrasonography and 10.5 mm and 2.4 mm at operation. On the left side the findings were 9.6 cm and 2.6 mm by ultrasonography and 11 cm and 2.6 mm at operation. There was one wound complication in an IEGA harvest site that had a body wall thickness of less than 4 cm (1/23; 4.2%), but all four sites with a body wall thickness of 4 cm or greater developed wound complications (4/4; 100%). CONCLUSION: The use of duplex scanning of the IEGA before operation provided excellent information about the length, diameter, depth, and patency of the vessel. Preoperative scanning prevented unnecessary dissection when the IEGA was not of adequate length or diameter. It was also very useful in providing information regarding risk of wound complications in obese patients.

Chemotherapy for acute lymphocytic leukemia: cognitive and academic sequelae.

Iatrogenic cognitive impairments have been reported for survivors of childhood leukemia after prophylactic central nervous system therapy with craniospinal radiation. To determine whether chemotherapy alone might be a source of central nervous system damage, we assessed in a cross-sectional design the cognitive and academic functioning of 48 children with acute lymphocytic leukemia who were at various stages in their treatment or who had completed treatment. The off-therapy patients who had completed a 3-year course of chemotherapy were more impaired in tasks of higher-order cognitive functioning than were those children whose leukemia had been newly diagnosed and those children whose diagnoses had been 1 year earlier. Off-therapy patients also had concomitant diagnosable learning disabilities in mathematics. We recommend appropriate liaison and special education placements, as well as continued evaluation of cognitive and leaning functioning of children treated for moderate-risk acute lymphocytic leukemia who receive chemotherapy alone.

Early language and communicative abilities of children with periventricular leukomalacia.

Ten 2-year-old children with periventricular leukomalacia (PVL), a brain injury associated with prematurity, were evaluated using language samples. Five children scored less than 80 on cognitive testing (delayed). Five children with this disorder and normal cognitive scores were assessed at two ages, matched with the delayed group on CA and developmental level. The delayed group produced significantly fewer lexical tokens and spontaneous verbal utterances than did the CA-matched group. No significant differences were observed between the delayed group and either comparison group on other measures of lexicon, grammar, or communication. The data demonstrate a relation between cognitive abilities and measures of verbal productivity in children with PVL.