Safety of aerosol therapy in children during noninvasive ventilation with helmet and total face mask.

PURPOSE: To evaluate the consequences of using nebulized drugs in patients subjected to noninvasive ventilation (NIV) with total face mask (TFM) and helmet. DESIGN: A descriptive analytical study of a prospective patient cohort was carried out. AMBIT: Pediatric intensive care unit (PICU) of a tertiary hospital. PATIENTS: Consecutive sampling was used to include all patients admitted to the PICU and requiring NIV with helmet or TFM over a period of 29 months. No patients were excluded. INTERVENTIONS: Nebulized treatment was added according to medical criteria. VARIABLES OF INTEREST: Independent variables were age, sex, diagnosis, disease severity, ventilation parameters and nebulized drugs (if administered). Secondary outcomes were duration and failure of NIV, and length of PICU stay. RESULTS: The most frequent diagnoses were bronchiolitis (60.5%) and asthma (23%). Patients received NIV for a median of 43h. Nebulized drugs were administered in 40% of the cases during NIV, and no adverse effects were registered. Using Bayesian statistics, the calculated probability of suffering an adverse effect was 1.3% with helmet and 0.5% with TFM (high density 95% probability intervals). Patients with helmet and nebulized therapy were in more serious condition than those who did not receive nebulization; nevertheless, no differences were observed regarding the need to change to bilevel modality. With TFM, PICU stay was shorter for the same degree of severity (p=0.033), and the NIV failure rate was higher in patients who did not receive inhaled drugs (p=0.024). CONCLUSIONS: The probability of suffering an adverse effect related to nebulization is extremely low when using a helmet or TFM. Inhaled therapy with TFM may shorten PICU stay in some patients.

[Congenital anomalies of the kidney and urinary tract. A vision for the paediatrician]. / Anomalías nefrourológicas congénitas. Una visión para el pediatra.

The congenital abnormalities of kidney and urinary tract (CAKUT) are disorders with a high prevalence in the general population, with urinary tract dilations being the most frequent. CAKUT also account for the most important cause of chronic kidney disease in childhood. This paper focuses on the role of the primary care paediatrician in the diagnosis, assessment, and follow-up of children with CAKUT, with special emphasis on the associated urinary tract infections, the progression toward chronic renal failure, and the genetic basis.

Increased body weight and decreased radial cross-sectional dimensions in girls with forearm fractures.

A large number of children sustain fractures after relatively minor trauma and several investigators have associated these fractures to a deficient accumulation of bone during growth. This study was conducted to better characterize the skeletal phenotype associated with low-energy impact fractures of the forearm in girls. The densities of cancellous, cortical, and integral bone and the cross-sectional area were measured in the radius of 100 healthy white girls (aged 4-15 years) using computed tomography (CT); 50 girls had never fractured and 50 girls had sustained a forearm fracture within the previous month. Fractured and nonfractured groups were matched for age, height, weight, and Tanner stage of sexual development. Compared with controls, girls with fractures had, on average, 8% smaller cross-sectional area at the distal radius (1.82 +/- 0.50 cm2 vs. 1.97 +/- 0.42 cm2; p < 0.0001) but similar cancellous, integral, and cortical bone densities. Neither radial length nor the amount of fat or muscle at the midshaft of the radius differed between girls with and without fractures. Both study subjects and matched controls were overweight. Although mean height was at the 50th percentile, mean weight was at the 90th percentile for age-adjusted normal values. Girls who sustain forearm fractures after minor trauma have small cross-sectional dimensions of the radius and tend to be overweight. The smaller cross-sectional area confers a biomechanical disadvantage that, coupled with the greater body weight, increases the vulnerability to fracture after a fall.

Early identification of children predisposed to low peak bone mass and osteoporosis later in life.

The amount of bone that is gained during adolescence is the main contributor to peak bone mass, which, in turn, is a major determinant of osteoporosis and fracture risk in the elderly. We examined whether computed tomography measurements for the density and the volume of bone in the axial and the appendicular skeletons could be tracked through puberty in 40 healthy white children (20 girls and 20 boys). Longitudinal measurements of the cross-sectional area and cancellous bone density of the vertebral bodies and the cross-sectional and cortical bone areas of the femurs at the beginning of puberty accounted for 62-92% of the variations seen at sexual maturity; on average, 3 yr later. When baseline values for these bone traits were divided into quartiles, a linear relation across Tanner stages of sexual development was observed for each quartile in both girls and boys. The regression lines differed among quartiles for each trait, paralleled each other, and did not overlap. Thus, we are now in a position to identify those children who are genetically prone to develop low values for peak bone mass and toward whom osteoporosis prevention trials should be geared.

Evaluation of the effects of oxandrolone on malnourished HIV-positive pediatric patients.

OBJECTIVE: To determine the safety and efficacy of anabolic therapy to prevent or reverse wasting and malnutrition in human immunodeficiency virus (HIV)-infected pediatric patients. The anabolic steroid, oxandrolone, was evaluated because of its safe and effective use in other pediatric conditions. METHODS: Nine HIV-positive children who were malnourished or at risk for malnutrition (4 females, 5 males; 4-14 years of age) took oxandrolone for 3 months (.1 mg/kg/day orally). Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels, complete blood cell count (CBC) and chemistry profile, endocrinologic studies, resting energy expenditure, respiratory quotient, nutritional measures, body composition assessment with quantitative computed tomography, and skinfold body composition measurements were determined before treatment, during treatment (3 months), and for 3 months after treatment. Statistical analyses were completed using the Friedman two-way analysis of variance and Spearman correlation tests. RESULTS: No adverse clinical or laboratory events or changes in Tanner staging or virilization occurred. Quantitative HIV ribonucleic acid polymerase chain reaction and CD4(+) T-cell levels did not change significantly. Insulin-like growth factor 1 increased, suggesting an anabolic effect of treatment. The rate of weight gain increased during treatment and was maintained after treatment. Linear growth continued and was maintained throughout treatment, whereas bone age did not increase significantly. Anthropometric assessments indicated an increase in muscle mass and a decrease in fat while patients were on treatment, and a mild decrease of muscle and increased fat posttreatment. Likewise, computed tomography scan results demonstrated similar changes in muscle mass. Resting energy expenditure and respiratory quotient remained stable throughout treatment and follow-up. No significant changes were seen in the quality of life questionnaire. CONCLUSIONS: Treatment with oxandrolone for 3 months in HIV-infected children was well-tolerated, safe, and associated with markers of anabolism. The latter effect was maintained partially for 3 months after discontinuation of a 3-month course of therapy. Additional studies are needed to assess the potential benefits and risks of a longer course of therapy or a higher dose of oxandrolone in HIV-infected children.

Differential effect of race on the axial and appendicular skeletons of children.

The prevalence of osteoporosis and the incidence of fractures are substantially lower in black than in white subjects, a finding generally attributed to racial differences in adult bone mass. Whether these racial differences are present in childhood is the subject of considerable interest, as the amount of bone gained during growth is a major determinant of future susceptibility to fractures. We measured the density and size of the vertebrae and femurs of 80 black and 80 white healthy children, 8-18 yr of age, matched for age, gender, height, weight, and stage of sexual development, using computed tomography. Race had a significant and differential effect on the bones in the axial and appendicular skeletons. In the axial skeleton, black children had greater cancellous bone density, but similar cross-sectional area of the vertebral bodies. In contrast, in the appendicular skeleton, black children had greater femoral cross-sectional area, but similar cortical bone area and cortical bone density. Compared to white children, vertebral bone density and femoral cross-sectional area at sexual maturity were, on the average, 10.75% and 5.7% higher, respectively, in black children. Such significant variations may contribute to the racial differences in the prevalence of osteoporosis between black and white adults.

Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent.

BACKGROUND: Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D-receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. METHODS: We identified three allelic variants of the vitamin D-receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D-receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. RESULTS: The vitamin D-receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P=0.008 and P=0.04, respectively) and 8 to 10 percent higher vertebral bone density (P=0.01 and P=0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D-receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D-receptor genotypes. CONCLUSIONS: Vitamin D-receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.

Pathogenesis of osteosclerosis in autosomal dominant osteopetrosis.

OBJECTIVE: The purpose of this study was to determine if the generalized osteosclerosis seen on skeletal radiographs of patients with osteopetrosis is associated with an increase in bone density. SUBJECTS AND METHODS: Five children (three girls, two boys, 6-12 years old) with autosomal dominant osteopetrosis who had sustained a fracture with minimal trauma had the density and area of cortical bone at the midshaft of the femur and the amount of cancellous vertebral bone per voxel measured by quantitative CT. Values for five children with osteopetrosis were compared with measurements for two control groups of healthy subjects matched for age, sex, Tanner stage of sexual development, race, weight, and height. RESULTS: Both the area of femoral cortical bone and the amount of cancellous vertebral bone per voxel were significantly greater in the children with osteopetrosis than in the healthy children. The density of bone in the children with osteopetrosis was the same as the density in the healthy subjects. Neither sex, age, height, or weight influenced bone density, and values were similar for all 15 children. CONCLUSION: The osteosclerosis depicted on skeletal radiographs of patients with osteopetrosis results from an increase in the amount of bone, not from an increase in the percentage of mineralized bone per unit volume of tissue.

Osteopenia in children: CT assessment.

PURPOSE: To assess the value of computed tomographic (CT) measurements of cortical bone in children with osteopenia. MATERIALS AND METHODS: The area and density of cortical bone in the midshaft of the femur were measured with CT in 37 children with osteopenia. Twenty had osteoporosis in one leg, nine had osteogenesis imperfecta (IO), and eight had vitamin D-resistant rickets. Comparisons were made between the CT measurements of the normal and abnormal extremities and between patients with OI or rickets and a group of 17 healthy, matched children. RESULTS: Sex, age, height, and weight did not influence cortical bone density; values were similar for the 17 control subjects. Children with osteoporosis and IO had reduced bone area but normal bone density. Compared with control subjects, patients with rickets had similar bone area but reduced bone density (869 mg/cm3 K2HPO4 +/- 79 [standard deviation] vs 1,132 mg/cm3 K2HPO4 +/- 41). CONCLUSION: CT measurements of area and density of cortical bone aided the differentiation of the various disorders that cause osteopenia in children.

Inhomogeneity in body fat distribution may result in inaccuracy in the measurement of vertebral bone mass.

When bone mineral content (BMC) is measured by dual X-ray absorptiometry (DXA), the X-ray beam is attenuated by bone and soft tissue. Since the component of the attenuation caused by the soft tissue overlying bone cannot be measured, the attenuation caused by soft tissue adjacent to bone is measured and is used in the calculation of BMC. the assumption underlying this approach is that the amount and composition of this adjacent soft tissue is the same as overlying bone. The aim of this study was to examine the validity of this assumption by determining whether fat distribution over and adjacent to bone differ and whether this introduces accuracy errors in the measurement of BMC by postero-anterior (PA) and lateral scanning. BMC (posterior processes plus vertebral body, g) of the third lumbar vertebra was 17.3 +/- 0.7 by PA and 17. +/- 0.7 by lateral scanning in 27 premenopausal women (p = NS), but 2.7 g or 20% higher by PA than scanning in 27 postmenopausal women (14.4 +/- 0.7, 11.7 +/- 0.5, p<0.01). Thus, the respective diminutions across age by PA scanning was about half that by lateral scanning (16.8 +/- 3.9%, 31.2 +/- 3.0%, p<0.01). Percent fat in the soft tissue baseline (anterior to bone, ST-ant) used to derive BMC by lateral scanning by 2.6 +/- 0.7% in premenopausal women and 7.5 +/- 1.0% in postmenopausal women (both p<0.01). After adjusting for these differences in percent fat, BMC by PA and lateral scanning no longer differed.

Vertebral size in elderly women with osteoporosis. Mechanical implications and relationship to fractures.

Reductions in bone density are a major determinant of vertebral fractures in the elderly population. However, women have a greater incidence of fractures than men, although their spinal bone densities are comparable. Recent observations indicate that women have 20-25% smaller vertebrae than men after accounting for differences in body size. To assess whether elderly women with vertebral fractures have smaller vertebrae than women who do not experience fractures, we reviewed 1,061 computed tomography bone density studies and gathered 32-matched pairs of elderly women, with reduced bone density, whose main difference was absence or presence of vertebral fractures. Detailed measurements of the dimensions of unfractured vertebrae and the moment arm of spinal musculature from T12 to L4 were calculated from computed tomography images in the 32 pairs of women matched for race, age, height, weight, and bone density. The cross-sectional area of unfractured vertebrae was 4.9-11.5% (10.5 +/- 1.4 vs 9.7 +/- 1.5 cm2; P < 0.0001) smaller and the moment arm of spinal musculature was 3.2-7.4% (56.4 +/- 5.1 vs 53.1 +/- 4.4 mm; P < 0.0001) shorter in women with fractures, implying that mechanical stress within intact vertebral bodies for equivalent loads is 5-17% greater in women with fractures compared to women without fractures. Such significant variations are very likely to contribute to vertebral fractures in osteoporotic women.

Gender differences in vertebral body sizes in children and adolescents.

PURPOSE: To determine whether differences in vertebral bone densities or sizes account for gender differences in skeletal mass during growth. MATERIALS AND METHODS: Quantitative computed tomography (CT) was used to measure the densities of cortical and cancellous bone and dimensions of the lumbar vertebral bodies in 196 healthy children and adolescents, ages 4-20 years. RESULTS: Neither cancellous nor cortical bone densities differed between boys and girls with age or level of sexual development. In contrast, the cross-sectional areas of the vertebral bodies were greater in boys than girls throughout childhood and adolescence. Even when prepubertal children were matched for chronologic age, bone age, height, and weight, the size of the vertebral bodies was 17% greater in boys. This disparity in vertebral body size increased with level of sexual development and was greatest at sexual maturity. CONCLUSION: Lower vertebral bone mass of women as compared with men may result from early gender differences in the sizes of bones rather than differences in bone densities.

Gender differences in vertebral sizes in adults: biomechanical implications.

PURPOSE: To determine if vertebral bone densities or vertebral body sizes contribute to gender differences in vertebral bone mass in adults. MATERIALS AND METHODS: Cancellous and cortical bone densities and dimensions of three lumbar vertebrae in 25 women and 18 men were measured with quantitative computed tomography (CT) and statistically analyzed. RESULTS: Neither cancellous nor cortical vertebral bone densities differed in healthy adults. Vertebral bodies in women had lower cross-sectional areas (8.22 cm2 +/- 1.09 [standard deviation] versus 10.98 cm2 +/- 1.25, P < .001) and volumes (22.42 cm3 +/- 2.40 versus 30.86 cm3 +/- 2.6, P < .001). These differences also were evident in men and women matched for age, weight, vertebral bone density, and vertebral body height. Overall cross-sectional areas of vertebral bodies are 25% smaller in women than men. Vertebral bone densities do not differ between sexes. Estimates of mechanical stress within vertebral bodies are 30%-40% higher in women than men for equivalent applied loads. CONCLUSION: Smaller vertebral bodies in women confer biomechanical disadvantages that may contribute to more vertebral fractures in elderly women.

Age-related changes in cortical and cancellous vertebral bone density in girls: assessment with quantitative CT.

OBJECTIVE: Bone mass increases during growth, but little information is available about the changes in cortical and cancellous bone densities during skeletal development or their relative contributions to age-related increases in bone mass. Accordingly, separate measurements of cancellous and cortical bone density were done at each stage of sexual development in white girls during childhood and adolescence. SUBJECTS AND METHODS: Quantitative CT was used to measure the densities of cortical and cancellous bone of the lumbar spine in 96 healthy white girls 4-20 years old. The relationships among various anthropometric indexes, pubertal status, and corresponding densities of cortical and cancellous bone were then examined. RESULTS: Cortical bone density increased with age, and values were significantly correlated with the anthropometric indexes of height (r = .61), weight (r = .62), body mass index (r = .61), and muscle volume (r = .58). In contrast, cancellous vertebral bone density increased only during the later stages of puberty. Moreover, cancellous bone density in prepubertal girls was inversely related to age (r = -.27) as well as to both the volume (r = -.20) and the height (r = -.15) of the vertebral body. CONCLUSION: The results suggest that weight bearing and/or mechanical stresses are important determinants of cortical bone density in the lumbar spine throughout growth, whereas cancellous vertebral bone density is more strongly influenced by hormonal and/or metabolic factors associated with sexual development during late adolescence.

Effect of hypogonadism and deficient calcium intake on bone density in patients with galactosemia.

Forty children and adults with classic galactosemia had vertebral bone density determined by standard quantitative computed tomography at 3.4 to 44.2 years of age. Compared with age- and sex-matched control subjects, patients with galactosemia had diminished bone density (p = < 0.001). Prepubertal patients of both sexes had bone density determinations below those of the control group (p = 0.008); similar findings were seen in postpubertal patients as well (women, p = 0.001; men, p = 0.008). Women receiving replacement estrogen-progestin therapy for premature ovarian failure had abnormal bone density (136.3 +/- 17.3 mg/cm3 vs 166.0 +/- 17.5 mg/cm3 for control subjects; p = 0.002); patients with evidence of ovarian insufficiency not receiving replacement sex steroids had even lower bone density (92.4 +/- 14.3 mg/cm3 vs 160.2 +/- 20.2 mg/cm3 for control subjects; p < 0.001). Calcium intake for the entire galactosemia group was 540 +/- 344 mg/day. Calcium intake correlated positively with bone density in women given exogenous estrogen (r = 0.87; p = 0.002) and in men (r = 0.74; p = 0.009). Thus the diminished mineralization of bones appears to be another abnormality associated with galactosemia. The results of our study suggest that this is likely secondary to abnormal levels of sex steroids in female patients, low calcium intake, and perhaps an intrinsic defect in the normal galactosylation of the collagen matrix of bone caused by the enzyme defect. Strategies to improve bone formation should be considered to diminish morbidity in patients with this inborn error of metabolism.

Cytokine- and Pneumocystis carinii- induced L-arginine oxidation by murine and human pulmonary alveolar macrophages.

Lipopolysaccharide plus interferon gamma stimulated the L-arginine-.NO pathway of murine, but not human pulmonary alveolar macrophages. Pneumocystis carinii induced .NO production by both murine and human pulmonary alveolar macrophages suggesting that the parasite stimulates L-arginine oxidation in these cells. The potential anti-Pneumocystis activity of .NO warrants further study.