'Down the rabbit hole': enhancing the transition process for youth with cystic fibrosis and congenital heart disease by re-imagining the future and time.

BACKGROUND: Although the transition from paediatric to adult clinical care is an important one, the process is far from seamless. Little is known about the transition experiences of youth with cystic fibrosis (CF) and congenital heart disease (CHD). METHOD: Informed by the new social studies of childhood, this qualitative study adopted a thematic analytical approach in order to explore how 50 youth and 28 parents affected by CF and CHD at a large children's hospital in Canada negotiate constructions of 'normal developmental time'--in both anticipating and dealing with the transition from adolescence to adulthood. RESULTS: Illness appeared to render the future as an uncertain terrain for youth living with CF and CHD. Concerns related to deteriorating health and occupational restrictions in the future were paramount for these youth. For young women with CF and CHD, the loss of 'normal' gendered roles--such as motherhood--was also a distressing future concern. For youth living with CF and their parents in particular, time was thought to be stolen and the future was abbreviated. Despite these seemingly anxiety-inducing experiences, youth and their parents demonstrated considerable creativity as they devised strategies to deal with the future and stolen time. RECOMMENDATIONS AND CONCLUSION: In addition to challenging ideological assumptions about developmental time which may alienate youth with chronic illnesses, the results from this study suggest that attending to youth's temporal anxieties and future concerns may ultimately enhance the transition process for youth with CF and CHD.

The bone formation defect in idiopathic juvenile osteoporosis is surface-specific.

We have previously shown that idiopathic juvenile osteoporosis (IJO) is characterized by a decreased cancellous bone volume and a very low bone formation rate on cancellous surfaces. Whether IJO similarly affects cortical bone is unknown. We therefore compared tetracycline double-labeled transfixing iliac-crest bone biopsies from eight children with typical clinical features of IJO (six girls; age 10-12 years) and from nine children (four girls; age 9-12 years) without metabolic bone disease. No differences in intracortical remodeling activity were detected. Both structural parameters reflecting intracortical remodeling (cortical porosity, active canal diameter, and quiescent canal diameter) and bone surface-based metabolic parameters (osteoid, osteoblast, mineralizing, osteoclast and eroded surfaces, and bone formation rate) were similar in IJO patients and controls (p > 0.2 each, t-test). Although the internal cortex of the biopsy was thinner in IJO patients than in controls (660 +/- 170 microm vs. 980 +/- 320 microm; p = 0.02), there was no difference in the width of the external cortex (p = 0.36). In growing children, both cortices exhibit an external modeling drift. Therefore, the difference in internal cortical width point to a decreased modeling activity on the endocortical surface of the internal cortex. In fact, bone formation rate on this surface was 48% lower in IJO patients than in controls (82 +/- 45 microm(3)/microm(2) per year vs. 159 +/- 162 microm(3)/microm(2) per year). However, this difference did not achieve statistical significance (p = 0.21) due to the high variability of bone formation rate on modeling surfaces. The disturbance of bone remodeling in IJO is limited to cancellous bone, but there may be a modeling defect affecting the internal cortex. Thus, the process causing IJO appears to mainly affect bone surfaces that are in contact with the bone marrow cavity.

Ophthalmic manifestations of lightning strike.

Every year in the USA, 100-150 people die and 1000-1500 others are injured by lightning strikes. Ophthalmic and neurologic injuries from lightning strike are common. The most common permanent ocular sequela is cataract, but many areas of the eye can be affected. Prompt evaluation by an ophthalmologist is imperative for maximizing outcomes. Incidence and mechanisms of lightning strike injury are summarized, with special emphasis on the treatment of ocular injuries.

Deficient bone formation in idiopathic juvenile osteoporosis: a histomorphometric study of cancellous iliac bone.

Idiopathic juvenile osteoporosis (IJO), a rare cause of osteoporosis in children, is characterized by the occurrence of vertebral and metaphyseal fractures. Little is known about the histopathogenesis of IJO. We analyzed by quantitative histomorphometry iliac crest biopsies from 9 IJO patients (age, 10.0-12.3 years; 7 girls) after tetracycline labeling. Results were compared with identically processed samples from 12 age-matched children without metabolic bone disease and 11 patients with osteogenesis imperfecta type I. Compared with healthy controls, cancellous bone volume (BV) was markedly decreased in IJO patients (mean [SD]: 10.0% [3.1%] vs. 24.4% [3.8%]), because of a 34% reduction in trabecular thickness (Tb.Th) and a 37% lower trabecular number (Tb.N; p < 0.0001 each; unpaired t-test). Bone formation rate (BFR) per bone surface was decreased to 38% of the level in controls (p = 0.0006). This was partly caused by decreased recruitment of remodeling units, as shown by a trend toward lower activation frequency (54% of the control value; p = 0.08). Importantly, osteoblast team performance also was impaired, as evidenced by a decreased wall thickness (W.Th; 70% of the control value; p < 0.0001). Reconstruction of the formative sites revealed that osteoblast team performance was abnormally low even before mineralization started at a given site. No evidence was found for increased bone resorption. Compared with children with osteogenesis imperfecta (OI), IJO patients had a similarly decreased cancellous BV but a much lower bone turnover. These results suggest a pathogenetic model for IJO, in which impaired osteoblast team performance decreases the ability of cancellous bone to adapt to the increasing mechanical needs during growth. This will finally result in load failure at sites where cancellous bone is essential for stability.

Association of high-dose intravenous methylprednisolone with reversal of blindness from lightning in two patients.

OBJECTIVE: To report possibly beneficial effects of treatment with high-dose corticosteroids given intravenously to two patients with loss of vision after lightning strikes. DESIGN: Case reports. PARTICIPANTS: Two patients who suffered the effects of a lightning strike. INTERVENTION: High-dose intravenous methylprednisolone (NASCIS-2 Protocol). MAIN OUTCOME MEASURES: Vision recovery, pupil responses, and optic nerve appearance. RESULTS: One patient had unilateral ophthalmoscopically visible abnormality with light perception vision and a relative afferent defect in that eye; vision recovered to 20/25. The other patient had no light perception, nonreactive pupils, and normal fundus examinations in both eyes; vision recovered bilaterally to normal (20/20). CONCLUSIONS: High-dose intravenous corticosteroid treatment in these patients may have had a role in their visual recovery.

Total body bone mineral density in young children: influence of head bone mineral density.

Dual-energy X-ray absorptiometry (DXA) with its short scan time, low radiation dose, and high precision and accuracy have made this technique particularly suitable for measuring total body bone mineral density (TBMD) in children. Other published reports have related TBMD to age in children 2-18 years of age. However, in young normal children aged 2-9 years (51 girls, 43 boys), we found that regression equations for TBMD with age as the predictor did not explain enough of the variance to warrant their use for predicting TBMD (adjusted R2 0.47, females; 0.41, males). Subtotal BMD (TBMD-head BMD) is predicted better by age because of a possibly invalid adult algorithm for head BMD (adjusted R2 0.73, females; 0.71, males).

Influence of surface coverage with poly(ethylene oxide) on attachment of sterically stabilized microspheres to rat Kupffer cells in vitro.

The attachment to rat Kupffer cells of polymeric microspheres, sterically stabilized with different amounts of pendant poly(ethylene oxide) (PEO), was assessed in vitro. Four types of copolymer polystyrene (PS) microspheres were synthesized by variation of four possible monomer ratios that included styrene, methoxy-PEO-methacrylate (750 and 2000 mol. wt PEO) and allylurea. This produced poly(styrene-(methoxy-PEO)methacrylate) microspheres with hydrophilic side-groups of either urea (PS-U-PEO) and/or mixed molecular weight (750/2000 mol. wt) PEO (PS-U-M-PEO, PS-M-PEO), or single molecular weight (2000) PEO (PS-PEO) at their surfaces. The hypothesis was tested that increasing the total content of PEO comprising the steric barrier reduces attachment to cell surfaces. Attachment of PEO microspheres bearing the urea spacer and/or mixed molecular weight PEO was found to be intermediate between charge stabilized control PS and PEO (2000 mol. wt) bearing particles. Post-adsorption of different Poloxamer (PEO-poly(propylene oxide)-PEO) surfactants to the microspheres further decreased attachment. Significant negative linear correlations between surface PEO content, measured by electron spectroscopy for chemical analysis (ESCA), and attachment to Kupffer cells were demonstrated. Decreases in attachment also resulted with all graft PEO particles bearing adsorbed sodium dodecyl sulphate (SDS), whilst the attachment of SDS-treated PS control particles increased. It is proposed that trains of adsorbed graft PEO are displaced by the SDS to increase the effective fraction of graft PEO within the steric layer. Overall, increasing the amount of hydrophilic PEO in the steric layer, from graft and adsorbed sources, reduces the attachment of these particles to Kupffer cells in vitro.

Nephrocalcinosis in X-linked hypophosphatemia: effect of treatment versus disease.

While the literature has suggested that vitamin D and phosphate therapy benefits children, and possibly adults, with X-linked hypophosphatemia (XLH), there have been increasing reports of nephrocalcinosis by renal ultrasound examination in treated patients. Although it has been assumed that nephrocalcinosis is the result of treatment, there has been no systematic comparison of treated and untreated XLH patients with long-term follow-up. Therefore, we studied 10 adults and 4 children by renal ultrasound examination with no history of medical therapy and 10 adults and 8 children with a history of medical therapy. None of the untreated patients had nephrocalcinosis; 5 treated adults and 5 treated children had nephrocalcinosis. In 3 of 4 treated children, serial renal ultrasounds did not show progression of the nephrocalcinosis. One patient progressed from baseline to year 1 only. Comparisons of means between treated patients without and with nephrocalcinosis showed statistically significant differences for urine calcium/creatinine ratios and urine phosphorus/creatinine ratios, differences not seen between untreated patients and treated patients without nephrocalcinosis. Phosphate dose, but not vitamin D dose, was statistically significantly different between the two treated groups. Our studies point to a convincing role for the association between nephrocalcinosis, as diagnosed by renal ultrasound examination, and medical therapy.

Effects of different techniques of endotracheal epinephrine administration in pediatric porcine hypoxic-hypercarbic cardiopulmonary arrest.

OBJECTIVE: To compare three endotracheal epinephrine instillation techniques in a pediatric porcine hypoxic-hypercarbic cardiopulmonary arrest model. DESIGN: Prospective, randomized, laboratory comparison of three instillation techniques. SETTING: Large animal research facility at a children's hospital. SUBJECTS: Thirty-six preadolescent anesthetized and paralyzed Yucatan swine (mean weight 10.0 +/- 1.9 kg) with apnea-induced hypoxic and hypercarbic cardiopulmonary arrest. INTERVENTIONS: After 8 mins of cardiopulmonary arrest and 1 min of cardiopulmonary resuscitation (CPR), 500 micrograms (51 +/- 9 micrograms/kg) of radiolabeled endotracheal epinephrine was administered by direct injection (n = 17), injection via feeding catheter (n = 10), or via monitoring lumen built into the sidewall of the endotracheal tube (n = 9). CPR was resumed and continued for 5 mins. If resuscitation occurred, monitoring was continued for 1 hr. Outcome variables included successful resuscitation, pulmonary distribution, heart rate, mean arterial pressure, plasma radiolabeled epinephrine counts, and total plasma epinephrine concentrations. Analysis by Fisher's exact test, one-way analysis of variance and Pearson's phi coefficient was performed. MEASUREMENTS AND MAIN RESULTS: Successful resuscitation occurred in 31% of all pigs with no difference between groups (p = .69). Bilateral distribution occurred in 39% with no difference between groups (p = .25). No correlation was noted between successful resuscitation and distribution (p = .65). HR, mean arterial pressure, plasma radiolabeled epinephrine counts, and total plasma epinephrine concentrations showed significant changes over time within groups, but no difference between groups at any time point. Adherence of the epinephrine dose to the endotracheal tube was < or = 1.5% in all cases. CONCLUSIONS: Instillation of 50 micrograms/kg of endotracheal epinephrine by three different techniques during pediatric porcine asphyxial arrest does not affect resuscitation rate, pulmonary distribution, hemodynamic response, or plasma exogenous and total epinephrine concentrations. No correlation was found between successful resuscitation and bilateral distribution. Therefore, currently recommended cumbersome endotracheal epinephrine instillation techniques may offer no resuscitation advantage over commonly used direct injection in this setting.

An in-vitro evaluation of coralline porous hydroxyapatite as a scaffold for osteoblast growth.

The purpose of this study was to determine the potential of coralline calcium phosphate ceramics to support osteoblast growth for a proposed bone-ceramic composite for skeletal tissue repair. The goal was the development of a matrix with both osteogenic and osteoconductive properties, as compared to ceramic alone, which is solely osteoconductive. MC3T3-E1 osteoblast-like cells were seeded onto sintered and non-sintered porous coralline hydroxyapatite (HA), and onto non-porous hydroxyapatite discs. These in-vitro studies demonstrated that coralline HA supported the growth of osteoblast-like cells. Porous discs supported higher numbers of cells than non-porous discs. Sintering encouraged cell growth, with higher numbers of cells adhered to sintered porous HA discs by day seven. The results suggest that HA can provide a support for osteoblast cells as part of a matrix which may prove to be osteogenic in vivo and may, accordingly, enhance the bone repair process.

Nitrogen balance in extremely low birth weight infants with nonoliguric hyperkalemia.

We measured nitrogen balance and urinary 3-methylhistidine molar ratios in 33 extremely low birth weight infants (12 with hyperkalemia and 21 without) for the first 3 days of life. Although all infants were in negative nitrogen balance during the study, there was no difference in the degree of negative nitrogen balance between the two groups. There was also no difference in the 3-methylhistidine/creatinine molar ratios, indicating that muscle protein catabolism did not differ. We conclude that it is unlikely that catabolism contributes to the development of nonoliguric hyperkalemia in extremely low birth weight infants.

In vivo evaluation of protein adsorption to sterically stabilised colloidal carriers.

A diffusion chamber implanted intraperitoneally in the rabbit was employed as an in vivo model to evaluate the interaction of peritoneal proteins with block copolymer (poloxamer and poloxamine)-coated polystyrene microspheres (PS). Using a desorption technique followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, six proteins of 94, 86, 66, 53, 40, and 20 kDa were desorbed from the carrier systems after incubation with peritoneal fluid in vitro. The 40- and 20-kDa proteins dominated the protein profile. A similar pattern was observed when proteins were desorbed from PS microspheres removed after 24-h implantation in chambers in the peritoneal cavity, although the protein profile was dominated by the 94- and 53-kDa proteins. In general, coating of PS with block copolymers reduced the amount of protein bound to the microspheres in vitro and in vivo but did not change the types of proteins bound.

Use of polyphosphazenes for skeletal tissue regeneration.

The hydrolytically unstable polyphosphazenes, poly [(imidazolyl) (methylphenoxy) phosphazenes] and poly [ethyl glycinato) (methylphenoxy) phosphazenes], were studied as potential polymeric supports for cells in tissue regeneration. For bone repair, their specific function would be to support osteoblast growth, forming a bone-polymer matrix. MC3T3-E1 cells (an osteogenic cell line) were seeded onto polymer matrices and cell adhesion and growth as well as polymer degradation were examined. Both imidazolyl- and ethyl glycinato-substituted polyphosphazenes supported the growth of MC3T3-E1 cells. An increase in the content of the imidazolyl side group resulted in a reduction in cell attachment and growth on the polymer surface and an increase in the rate of degradation of the polymer. In contrast, substitution with the ethyl glycinato group favored increased cell adhesion and growth and also an increase in the rate of degradation of the polymers. Thus, the polyphosphazenes represent a system whereby cell growth and degradation can be modulated by varying the nature of the hydrolytically unstable side chain. This in vitro evaluation suggests that the polyphosphazenes may be suitable candidate biomaterials for the construction of a cell-polymer matrix for tissue regeneration.

Influence of block copolymers on the adsorption of plasma proteins to microspheres.

SDS-PAGE in combination with densitometry has been used to evaluate the adsorption of plasma and serum proteins to polystyrene microspheres (PS) coated with block copolymers of the poloxamer and poloxamine series. The protein-resistant nature of coated PS was demonstrated for these systems when incubated in dilutions of plasma and serum. The total amount of protein and the type of proteins adsorbed were dependent on the plasma and serum incubation concentration used. At 0.3% serum concentrations the total amount of protein adsorbed was found to be related to the polyoxyethylene (PEO) chain length of the block copolymer, whilst at 0.3% or 50% plasma concentrations a relationship was shown between the polyoxypropylene (PPO) chain and the plasma protein adsorption for the range of block copolymers studied. Immunoblotting studies revealed the adsorption of immunoglobulin G, complement C3, transferrin and fibronectin to all microspheres previously incubated in 50% serum and plasma, whilst fibrinogen was also adsorbed after incubation in 50% plasma; with similar quantities of each protein adsorbed to PS and block copolymer-coated PS.

Decreased erythrocyte Na+,K(+)-ATPase activity associated with cellular potassium loss in extremely low birth weight infants with nonoliguric hyperkalemia.

To determine whether a shift of potassium ions from the intracellular space to the extracellular space accounts, in part, for the hyperkalemia seen in extremely low birth weight infants, we examined potassium concentration in serum and erythrocytes from extremely low birth weight infants with hyperkalemia (n = 12) or with normokalemia (n = 27). In addition, to determine whether the shift of potassium was associated with low sodium-potassium-adenosinetriphosphatase (Na+,K(+)-ATPase) activity, we studied the activity of ATPase in the last 16 infants enrolled in the study. Fluid intake and output were measured during the first 3 days of life. Infants were considered to have hyperkalemia if the serum potassium concentration was 6.8 mmol/L or greater. Blood was obtained daily for intracellular sodium and potassium levels by means of lysis of erythrocytes. The remaining erythrocyte membranes were frozen and analyzed for Na+,K(+)-ATPase activity. There were significantly lower intracellular potassium/serum potassium ratios in the infants with hyperkalemia for each day of the 3-day study (p < 0.001). In the hyperkalemic group, there was lower Na+,K(+)-ATPase activity than in the infants with normokalemia (p = 0.006). Low Na+,K(+)-ATPase activity was associated with lower intracellular potassium/serum potassium ratios (p = 0.006), higher serum potassium values (p = 0.02), and lower intracellular potassium concentration (p = 0.009). The urinary data demonstrated that there was no difference in glomerulotubular balance between the two groups. We conclude that nonoliguric hyperkalemia in extremely low birth weight infants may be due, in part, to a shift of potassium from the intracellular space to the extracellular space associated with a decrease in Na+,K(+)-ATPase activity.

Osteoblast-like cell (MC3T3-E1) proliferation on bioerodible polymers: an approach towards the development of a bone-bioerodible polymer composite material.

An osteogenic cell line (MC3T3-E1) was used to study the potential of bioerodible polymers and ceramics to support osteoblast growth for a proposed bone-polymer composite for skeletal tissue repair. MC3T3-E1 cells were seeded on to 50:50 poly(lactide-co-glycolide), hydroxyapatite, 50:50 hydroxyapatite/poly(lactide-co-glycolide), and the poly(anhydride), poly(bis(p-carboxyphenoxy) propane surfaces. Cell attachment and growth on these surfaces was found to be highest on poly(lactide-co-glycolide), the least on hydroxyapatite and hydroxyapatite/poly(lactide-co-glycolide) combinations gave intermediate values. The order of adhesion and growth of MC3T3-E1 cells on the polymer and ceramic systems was poly(lactide-co-glycolide) is greater than hydroxyapatite/poly(lactide-co-glycolide) which is greater than hydroxyapatite. Negligible growth was found on poly(bis(p-carboxyphenoxy) propane. High alkaline phosphatase activity for the cells grown on poly(lactide-co-glycolide) and hydroxyapatite/poly(lactide-co-glycolide) confirmed retention of the osteoblast phenotype. This in vitro evaluation suggests that poly(lactide-co-glycolide) and hydroxyapatite/poly(lactide-co-glycolide) combinations may be candidate biomaterials for the construction of a cell-polymer matrix for skeletal tissue regeneration.

Human serum albumin as a probe for surface conditioning (opsonization) of block copolymer-coated microspheres.

The adsorption of human serum albumin to polystyrene microspheres sterically stabilized with block copolymers, was investigated using photon correlation spectroscopy and laser doppler anenometry. The block copolymers used were non-ionic surfactants of the poloxamer and poloxamine series made of polyoxyethylene and polyoxypropylene chains. Photon correlation spectroscopy and laser doppler anenometry showed that the coating reduced the adsorption of the protein to the polystyrene microspheres surface. Quantitative studies using 125I-labelled human serum albumin and sodium dodecyl sulphate-polyacrylamide gels (in combination with densitometry), were employed to evaluate the adsorption of human serum albumin to uncoated and coated polystyrene microspheres. They confirmed that the hydrophilic polyoxyethylene steric layer, created by coating with the block copolymers, reduced the adsorption of human serum albumin. Moreover, the amount of human serum albumin adsorbed was related to the polyoxyethylene content of the block copolymers.

Renal function and renal failure in the newborn.

Renal function in the newborn infant varies with conceptual age and should be evaluated in this context. Very preterm infants less than 34 weeks' conceptual age have reduced GFR and tubular immaturity in the handling of filtered solutes when compared to term infants. Premature infants between 34 and 37 weeks' conceptual age undergo rapid maturation of renal function similar to term infants, with establishment of glomerulotubular balance early in the postnatal period. ARF in neonates differs from that seen in older children and adults in that ischemic (e.g., hypoxic) insults and congenital malformations constitute the major pathophysiologic mechanisms responsible for clinically observed oliguria and azotemia. Principles of conservative management are similar to those used in older children except for the greatly increased insensible water loss requirements of the very preterm and premature infant. Technical advances have added peritoneal dialysis and CAVH to the therapeutic regimen for persistent ARF or life-threatening complications of reduced renal function.