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.

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.

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.

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.

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.

Neonatal osteomyelitis.

Thirty-four neonates with osteomyelitis were reviewed. The hip (19) was the most common site involved. Swelling and pseudoparalysis were the most significant local signs. Radiographic abnormalities, such as metaphyseal rarefaction and/or joint subluxation were found on the initial radiographs in 18 of the 19 hips involved. All patients were treated with antibiotics and all infections involving joints were drained surgically. Good results were achieved in 75% of all sites and in 68% of hips.

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.

Remodelling of angular deformity after femoral shaft fractures in children.

We reviewed 28 children with unilateral middle-third fractures of the femoral shaft who had an angular deformity after union of 10 degrees to 26 degrees. At an average follow-up of 45 months (20 to 66), we measured remodelling of the proximal physis, the distal physis and the femoral shaft. The average correction was 85% of the initial deformity. We found that 74% of correction occurred at the physes and only 26% at the fracture site. Neither the direction nor the magnitude of the angulation much influenced the degree of remodelling. Younger children remodelled only a little better than older children. We conclude that in children under 13 years of age, malunion of as much as 25 degrees in any plane will remodel enough to give normal alignment of the joint surfaces.

Calcaneus deformity in the ambulant patient with myelomeningocele.

We reviewed our experience of tibialis anterior transfer and anterior release for calcaneus deformity in 46 feet of 26 ambulant patients with myelomeningocele. At an average follow-up of 8.4 years (2 to 17.6) there were 89% who had satisfactory results; 64% of the patients having tibialis anterior transfers were able to stand on their toes. Hip abductor power was a good predictor of a functional transfer. Pre-operative trophic ulceration of the heel increased from 3.2% to 33% if surgery was delayed. Secondary deformities, two-thirds of them into valgus, developed in 76% of feet.

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.

Severe disseminated staphylococcal disease associated with osteitis and septic arthritis.

We reviewed the records of 1,156 patients treated for acute staphylococcal osteitis or septic arthritis over a 12-year period; 38 had been critically ill with evidence of multiple-organ involvement and 30 (79%) had features of the toxic shock syndrome. The mortality rate of these 38 patients was 13% and the long-term orthopaedic complication rate was 39%. The diagnosis and management of patients with osteitis or septic arthritis, disseminated staphylococcal disease, and the toxic shock syndrome is discussed.

Fracture-separation of the distal humeral epiphysis.

We have reviewed 12 cases of fracture-separation of the distal humeral epiphysis, three of which were initially misdiagnosed as fractures of the lateral condyle and one as an elbow dislocation. Cubitus varus deformity is as common after this fracture-separation as it is following supracondylar fracture, and is most common in children under two years of age. Closed reduction and simple immobilisation is adequate for the older child, but we recommend for those under two years of age that closed reduction should be followed by percutaneous pinning, so that the carrying angle can be assessed immediately after reduction. If the elbow is then in varus the wires should be removed, reduction repeated and treatment by straight lateral traction used to maintain a valgus carrying angle.

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.

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.

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.

The unstable hip and mid-lumbar myelomeningocele.

We reviewed 55 patients with mid-lumbar myelomeningocele (L3 and L4) first seen over a 17-year period from 1970 to 1986 and followed up for an average of ten years. We assessed a number of factors which might affect hip stability and ability to walk, recording the natural history of clinical and radiological hip deformity. Two-thirds of the hips had become dislocated or subluxed by the end of the first year of life, involving 86% of hips in patients with an L3 level and 45% of those with an L4 level. All the hips that developed instability secondary to muscle imbalance did so within the first year. The neurological level was the most significant determinant of walking ability: all patients with L4 neurological levels could walk but only one-third of those with L3 lesions could do so. Hip stability, intelligence quotient and fixed deformity did not influence walking ability.