French Osteotomy for Cubitus Varus in Children: A Long-term Study Over 27 Years.

BACKGROUND: Cubitus varus is a cosmetically unacceptable complication of supracondylar fractures of the elbow in children. We have performed the lateral closing wedge (French) osteotomy to correct the varus for 27 years. More complex osteotomies have been described to correct the associated hyperextension and internal rotation deformities and to prevent a prominent lateral condyle. METHODS: We retrospectively reviewed 90 consecutive patients (1986 to 2012). The mean age of the patients at surgery was 8.2 years (3 to 14 y). The varus angle (mean, 21.4 degrees; range, 8 to 40 degrees) was assessed preoperatively with the humero-elbow-wrist angle. The postoperative carrying angle (mean, 10.4 degrees) and the preoperative and postoperative range of movement were assessed clinically. The lateral condylar prominence index (LCPI) was retrospectively measured at union. RESULTS: Eighty-four (93.3%) of the patients had a good or excellent result. Six (6.7%) had a poor result (residual varus, loss of >20 degrees of preoperative range of flexion or extension or a complication necessitating resurgery). There were no neurovascular complications. The mean LCPI was +0.14. CONCLUSIONS: The results of the French osteotomy are comparable with the more technically demanding dome, step-cut translation, and multiplanar osteotomies, with a lower complication rate. The literature reports adequate remodeling of the hyperextension deformity (≤10 y) and the LCPI (≤12 y), and that the internal rotation deformity is well tolerated by the patient. LEVEL OF EVIDENCE: Level IV-case series.

Asthma and allergy development: contrasting influences of yeasts and other fungal exposures.

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Wheeze in infancy: protection associated with yeasts in house dust contrasts with increased risk associated with yeasts in indoor air and other fungal taxa.

BACKGROUND: While fungal exposures are assumed to provoke wheeze through irritant or allergenic mechanisms, little is known about the differential effects of indoor and outdoor fungi on early-life wheeze. METHODS: In a Boston prospective birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and outdoor air were measured at the age of 2-3 months. Wheeze was determined using bimonthly telephone questionnaires. Odds ratios were estimated for an interquartile increase in fungal natural log-transformed concentrations, adjusting for predictors of wheeze and potential confounders. RESULTS: Increased odds of 'any wheeze' (≥1 vs 0 episodes) by age one were positively associated with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR = 1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (≥2 vs <2 episodes) by age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was associated with any wheeze for children with maternal mold sensitization [OR = 9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR = 1.32; (0.79-2.20)]. CONCLUSIONS: While wheeze rates were higher with exposures to fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts in the home had a strong protective association with wheeze in infancy. Molecular microbiologic studies may elucidate specific components of innate microbiologic stimulants that lead to contrasting effects on wheeze development.

The effect of percutaneous pin fixation in the treatment of distal femoral physeal fractures.

Distal femoral physeal fractures in children have a high incidence of physeal arrest, occurring in a mean of 40% of cases. The underlying nature of the distal femoral physis may be the primary cause, but other factors have been postulated to contribute to the formation of a physeal bar. The purpose of this study was to assess the significance of contributing factors to physeal bar formation, in particular the use of percutaneous pins across the physis. We reviewed 55 patients with a median age of ten years (3 to 13), who had sustained displaced distal femoral physeal fractures. Most (40 of 55) were treated with percutaneous pinning after reduction, four were treated with screws and 11 with plaster. A total of 40 patients were assessed clinically and radiologically after skeletal maturity or at the time of formation of a bar. The remaining 15 were followed up for a minimum of two years. Formation of a physeal bar occurred in 12 (21.8%) patients, with the rate rising to 30.6% in patients with high-energy injuries compared with 5.3% in those with low-energy injuries. There was a significant trend for physeal arrest according to increasing severity using the Salter-Harris classification. Percutaneous smooth pins across the physis were not statistically associated with growth arrest.

Multiple microbial exposures in the home may protect against asthma or allergy in childhood.

BACKGROUND: Experimental animal data on the gram-negative bacterial (GNB) biomarker endotoxin suggest that persistence, dose, and timing of exposure are likely to influence its effects on allergy and wheeze. In epidemiologic studies, endotoxin may be a sentinel marker for a microbial milieu, including gram-positive bacteria (GPB) as well as GNB, that may influence allergy and asthma through components (pathogen-associated molecular patterns) that signal through innate Toll-like receptor pathways. OBJECTIVE: To determine the influence of current GNB and GPB exposures on asthma and allergic sensitization in school-aged children. METHODS: We examined the relationship between bacterial biomarkers and current asthma and allergic sensitization in 377 school-aged children in a birth cohort study. We then evaluated the effects of school-aged endotoxin, after controlling for exposure in early life. RESULTS: Exposure to GNB was inversely associated with asthma and allergic sensitization at school age [for >median endotoxin: prevalence odds ratio (POR)=0.34, 95% CI=0.2-0.7, for current asthma and prevalence ratio=0.77, 95% CI=0.6-0.97, for allergic sensitization]. In contrast, elevated GPB in the bed was inversely associated with current asthma (POR=0.41, 95% CI=0.2-0.9) but not with allergic sensitization (POR=1.07, 95% CI=0.8-1.4). School-aged endotoxin exposure remained protective in models for allergic disease adjusted for early-life endotoxin. CONCLUSION: Both GNB and GPB exposures are associated with decreased asthma symptoms, but may act through different mechanisms to confer protection. Endotoxin exposure in later childhood is not simply a surrogate of early-life exposure; it has independent protective effects on allergic disease.

Mouse allergen exposure, wheeze and atopy in the first seven years of life.

BACKGROUND: Little is known about mouse allergen exposure in home environments and the development of wheezing, asthma and atopy in childhood. OBJECTIVE: To examine the relation between mouse allergen exposure and wheezing, atopy, and asthma in the first 7 years of life. METHODS: Prospective study of 498 children with parental history of allergy or asthma followed from birth to age 7 years, with longitudinal questionnaire ascertainment of reported mouse exposure and dust sample mouse urinary protein allergen levels measured at age 2-3 months. RESULTS: Parental report of mouse exposure in the first year of life was associated with increased risk of transient wheeze and wheezing in early life. Current report of mouse exposure was also significantly associated with current wheeze throughout the first 7 years of life in the longitudinal analysis (P = 0.03 for overall relation of current mouse to current wheeze). However, early life mouse exposure did not predict asthma, eczema or allergic rhinitis at age 7 years. Exposure to detectable levels of mouse urinary protein in house dust samples collected at age 2-3 months was associated with a twofold increase in the odds of atopy (sensitization to >=1 allergen) at school age (95% confidence interval for odds ratio = 1.1-3.7; P = 0.03 in a multivariate analysis. CONCLUSIONS: Among children with parental history of asthma or allergies, current mouse exposure is associated with increased risk of wheeze during the first 7 years of life. Early mouse exposure was associated with early wheeze and atopy later in life.

Four decades of conjoined twins at Red Cross Children's Hospital--lessons learned.

Conjoined twins represent a rare but fascinating congenital condition, the aetiology of which remains obscure. Over the past four decades, the paediatric surgeons at Red Cross Children's Hospital have been involved in the management of 46 pairs of conjoined twins, of which 33 have been symmetrical and 12 asymmetrical. Seventeen symmetrical twins have undergone separation with 22 children (65%) surviving; all of the live asymmetrical twins survived separation. We describe the important features of this unique cohort, outline our approach to management and present the results of this approach. We consider some of the ethical and moral dilemmas we have confronted, and discuss the prenatal diagnosis, obstetric implications and postnatal care of these children, including the relevant investigations and anaesthetic and surgical management. Specific aspects related to the cardiovascular system, hepatobiliary and gastrointestinal tracts, urogenital tract, central nervous system and musculoskeletal system are highlighted.

Double-elevating osteotomy for late-presenting infantile Blount's disease: the importance of concomitant lateral epiphysiodesis.

We reviewed 34 knees in 24 children after a double-elevating osteotomy for late-presenting infantile Blount's disease. The mean age of patients was 9.1 years (7 to 13.5). All knees were in Langenskiöld stages IV to VI. The operative technique corrected the depression of the medial joint line by an elevating osteotomy, and the remaining tibial varus and internal torsion by an osteotomy just below the apophysis. In the more recent patients (19 knees), a proximal lateral tibial epiphysiodesis was performed at the same time. The mean pre-operative angle of depression of the medial tibial plateau of 49 degrees (40 degrees to 60 degrees ) was corrected to a mean of 26 degrees (20 degrees to 30 degrees ), which was maintained at follow-up. The femoral deformity was too small to warrant femoral osteotomy in any of our patients. The mean pre-operative mechanical varus of 30.6 degrees (14 degrees to 66 degrees ) was corrected to 0 degrees to 5 degrees of mechanical valgus in 29 knees. In five knees, there was an undercorrection of 2 degrees to 5 degrees of mechanical varus. At follow-up a further eight knees, in which lateral epiphysiodesis was delayed beyond five months, developed recurrent tibial varus associated with fusion of the medial proximal tibial physis.

Posterior iliac osteotomy in ischiopagus tetrapus twins.

Eight hemipelvises in ischiopagus tetrapus conjoined twins were assessed retrospectively to determine whether posterior iliac osteotomy is appropriate to reconstruct pelvic symmetry. Although clinical and radiological similarity exists with classic bladder exstrophy, axial and three-dimensional computed tomography showed the pelvic deformity to be very different. In classic bladder exstrophy, the deformity is one of shortening and external rotation of the anterior segment, and external rotation of the posterior segment. The deformity in the ischiopagus tetrapus pelvis is purely one of external rotation of the posterior segment. Posterior iliac osteotomy alone was therefore able to restore pelvic symmetry in seven of the eight hemipelvises, and prevented rediastasis of the symphysis pubis in all patients.

Pyogenic spondylitis and early tuberculous spondylitis in children: differential diagnosis with standard radiographs and computed tomography.

In a study of 23 patients, axial computed tomography (CT) was the most valuable modality to differentiate between early tuberculous (10 patients) and pyogenic spondylitis (13 patients). Tuberculous spondylitis showed large erosions with calcification, whereas pyogenic spondylitis showed multiple small well-defined erosions, mostly without calcification. Both groups had large or small paravertebral soft tissue swelling, with accompanying calcification, in six of the 10 patients with tuberculous spondylitis and in only one patient with pyogenic spondylitis. Tuberculous spondylitis showed larger intraspinal extradural abscesses, with calcification in 50% of cases, whereas pyogenic spondylitis demonstrated no calcification.

Midtarsal dislocations in children.

Four children with midtarsal dislocations are described. Two of the four patients had a delay in diagnosis because of associated midtarsal injuries detracting from the main pathology. The key pathology was a dislocation or subluxation of the calcaneocuboid joint. The lateral radiograph was the most consistent view in making the diagnosis.

A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study.

BACKGROUND: The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD. METHODS: Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess the safety of the material in this patient population. In addition, as a surrogate marker of efficacy, each subject underwent a variety of exercise tests before and after HBOC-201 was given. RESULTS: All HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061). CONCLUSIONS: HBOC-201 was safely administered to patients with SCD who were not in crisis at the time of study. Furthermore, following infusion of the study material, subjects with SCD performed the identical aerobic exercise-induced workload with an increase in heart rate that was significantly less than the increase observed in the subjects who received an infusion of the saline placebo. These safety and surrogate efficacy data support the notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.

Immunoglobulin allotypes and genetic susceptibility to invasive Haemophilus influenzae type b and Staphylococcus aureus infections in South African children.

OBJECTIVE: The purpose of this study was to determine whether the G2m(n), G1m(f) and Km(3) immunoglobulin allotypes have any association with susceptibility to invasive Haemophilus influenzae type b (Hib) and Staphylococcus aureus (S. aureus) infections in children. METHODS: Direct enzyme-linked immunosorbent assays with commercially available monoclonal antibodies were established to quantitate G2m(n) and G1m(f) allotypes. A qualitative enzyme-linked immunosorbent assay with polyclonal rabbit anti-Km(3) antibody was established for Km(3) determination. RESULTS: The G2m(n) marker occurred in 34.4% of the mixed ancestry population and 2.9% of the Black population. There was a significantly decreased frequency of the G2m(n) allotype in mixed ancestry children with Hib meningitis (8.5%) and Hib osteomyelitis/septic arthritis and a decreased frequency of Km(3) in black and mixed ancestry children with Hib meningitis. The frequency of G2m(n), G1m(f) and Km(3) allotypes in patients with S. aureus osteomyelitis/septic arthritis were not significantly different from normal population frequency. CONCLUSIONS: This study shows a clear association between the absence of the G2m(n) allotype in mixed ancestry children and susceptibility to invasive infections caused by H. influenzae and an association between the absence of Km(3) and Hib meningitis in both black and mixed ancestry children.

Tuberculosis of the knee in children.

We reviewed 33 children with tuberculosis of the knee treated during the period from 1979 to 1991. All were treated with triple chemotherapy, using rifampicin, isoniazid and pyrazinamide for nine months. No patient had a synovectomy; surgery was limited to open biopsy or salvage procedures such as posterior release and arthrodesis for late stages of the disease. The radiological appearance of the knee at presentation predicted the outcome. The 30 patients with stage-1 (normal) or stage-2 (osteomyelitic) disease had excellent or good results; the three with narrowed joint spaces in stage 3 or stage 4 (arthritic) had fair or poor results. Early active mobilisation, as against long-term immobilisation, seemed to have no effect on the outcome of stage-1 or stage-2 disease.

Tuberculosis of the hip in children.

We have reviewed 74 tuberculous hips in 73 children treated from 1950 to 1991. From 1979 to 1991 we treated 28 patients with rifampicin, isoniazid and pyrazinamide given for nine months (series A), using active mobilisation for the more recent cases. Before this, 46 hips had been treated with streptomycin and isoniazid with or without para-aminosalicyclic acid given for a mean of 18 months (series B), and all these patients were immobilised for a mean of 2.2 years. The radiological appearances at presentation as classified by Shanmugasundaram (1983) predicted the outcome. Most hips were of the 'normal' type (50% and 59% of series A and B respectively) followed by the dislocating type (25% and 13%) and the atrophic type (8% and 9%). There were good or excellent results in 93% of the 'normal' type. All the atrophic type had poor results. The dislocating type had a poor result if the joint space was narrow after reduction of the hip. Early mobilisation had no effect on the outcome of the 'normal' type of disease. The newer drug regimens allowed for shorter courses of treatment, but did not necessarily give a better outcome.

Isotope bone scanning for acute osteomyelitis and septic arthritis in children.

We prospectively studied 86 children to assess the value and accuracy of isotope bone scanning in the diagnosis of suspected acute haematogenous osteomyelitis and septic arthritis. The patients were scanned because of difficulty in localising the exact site of the pathology. Characteristic scan appearances were found. In osteomyelitis there was increased or decreased uptake extending beyond the confines of the joint capsule; in septic arthritis there was increased or decreased uptake on either side of the joint line, but largely limited to and uniform within the joint capsule. The bone-scan images were correlated with the final diagnosis in 34 sites of septic arthritis and in 62 sites of osteomyelitis. The overall accuracy of the bone scans was 81%. The predictive value for a positive scan to be correct was 100% for a cold scan and 82% for a hot scan. The main reason for a false-positive scan was contiguous soft-tissue infection. The predictive value for a negative scan to be correct was 63%. One reason for a false-negative scan was that the patient was in the transitional phase from cold to hot.

Chondrolysis in slipped upper femoral epiphysis. Long-term study of the aetiology and natural history.

Of 44 patients (55 hips) with slipped upper femoral epiphysis treated from 1963 to 1989, 13 (14 hips) developed chondrolysis. Eight hips had chondrolysis at the time of presentation, all in female patients who were either coloured or black and who had moderate or severe slips. The other six hips had persistent pin penetration of the joint; in five of these the pin penetrated the anterosuperior quadrant of the head. Removal of penetrating pins resulted in improvement in pain in all six hips and in the range of movement in four. Chondrolysis did not develop in any of 11 hips with transient intraoperative pin penetration. In hips with chondrolysis maximum joint-space narrowing developed within the first year; improvement in joint space and range of movement continued for up to three years after maximal involvement. At an average follow-up of 13.3 years no patient had pain but five hips were stiff.

Spondylolysis and spondylolisthesis after five-level lumbosacral laminectomy for selective posterior rhizotomy in cerebral palsy.

Of 163 children who have undergone five-level lumbosacral laminectomies for selective posterior rhizotomy, 20% of those re-X-rayed post-operatively (19/99) have developed incidental isthmic spondylolysis or grade I spondylolisthesis. The majority of patients were ambulatory, active, spastic diplegics. There were five children with isthmic defects at L3-4, three at L4-5 and 11 at L5-S1. Six of the 19 children had grade I spondylolisthesis, but none were symptomatic nor has there been any evidence of further slipping to date. It is postulated that the laminectomy, associated lordosis and increased mobility after rhizotomy may be factors in the causation.

Imaging in children with spinal tuberculosis. A comparison of radiography, computed tomography and magnetic resonance imaging.

We compared the usefulness of radiography, CT and MRI in 25 children with spinal tuberculosis. Radiography provided most of the information necessary for diagnosis and treatment. Axial CT was the most accurate method for visualising the posterior bony elements. Sagittal MRI best showed the severity and content of extradural compression and helped to differentiate between an abscess and fibrous tissue. The main value of CT and MRI is in the preoperative evaluation of the small proportion of patients who require surgical treatment for paraplegia.