Richard Browne

The neonatal blood count in health and disease.I. Reference values for neutrophilic cells

Reference ranges for absolute total neutrophils/mm3, absolute immature neutrophils/mm3, and the fraction of immature to total neutrophils (I:T proportion) during the first 28 days of life are developed from 585 peripheral blood counts obtained from 304 normal neonates and 320 counts obtained from 130 neonates with perinatal complications demonstrated to have no statistically significant effect on neutrophil dynamics. Perinatal factors other than bacterial disease which significantly alter neutrophil dynamics include maternal hypertension, maternal fever prior to delivery, hemolytic disease, and periventricular hemorrhage. The predictive value of these reference ranges in identifying bacterial disease in the first week of age varies with the neutrophil factor evaluated and the clinical setting. Neutropenia in the presence of respiratory distress in the first 72 hours had an 84% likelihood of signifying bacterial disease, whereas neutropenia in the presence of asphyxia had a 68% likelihood of signifying bacterial disease. An abnormal I:T proportion had an accuracy of 82% and 61%, respectively, in the same clinical settings. Elevations of either immature or total neutrophils were less specific. Interpretation of abnormal neutrophil factors must include consideration of both infectious and noninfectious perinatal events.

Measurement of scoliosis and kyphosis radiographs. Intraobserver and interobserver variation.

Interobserver variations for measurements of the Cobb angle on radiographs of patients who had kyphosis were comparable with those on the radiographs of patients who had scoliosis. Four staff orthopaedists and one physical therapist measured eight radiographs that showed scoliosis and twenty that showed kyphosis. The measurements were made on two occasions and in random order. For scoliosis, the average difference between readings was 3.8 degrees, and 95 per cent of the differences were 8 degrees or less (range, 0 to 10 degrees). These findings were in keeping with those of other published reports. For kyphosis, the average difference between readings was 3.3 degrees, and 95 per cent of the differences were 7 degrees or less (range, 0 to 30 degrees). One investigator rated the kyphosis radiographs with respect to clarity. There was a trend to less variation with clearer radiographs, but this was not significant. The end-vertebrae were pre-selected for some radiographs and were freely chosen by the interpreter for others. Reliability was not significantly improved when the end-vertebrae of the curve had been pre-selected. Using the statistical method called tolerance limits, we determined that if one were to be 95 per cent confident that a measured difference represented a true change, the difference would have to be 10 degrees for scoliosis radiographs and 11 degrees for kyphosis radiographs. The probability that a measured difference is due to measurement error alone (that is, a false-positive reading) was calculated.

Legg-Calve-Perthes disease. Part II: Prospective multicenter study of the effect of treatment on outcome.

BACKGROUND The treatment of Legg-Calve-Perthes disease has been based on uncontrolled retrospective studies with relatively small numbers of patients. This large, controlled, prospective, multicenter study was designed to determine the effect of treatment and other risk factors on the outcome in patients with this disorder. METHODS We enrolled 438 patients with 451 affected hips in a prospective multicenter study in which each investigator applied the same treatment method to each of his or her patients. The five treatment groups consisted of no treatment, brace treatment, range-of-motion exercises, femoral osteotomy, and innominate osteotomy. All patients were between 6.0 and 12.0 years of age at the onset of the disease, and none had had prior treatment. Three hundred and forty-five hips in 337 patients were available for follow-up at skeletal maturity. All hips were classified with the modified lateral pillar classification and the system of Stulberg et al. RESULTS There were no differences in outcome among the hips with no treatment, those treated with bracing, and those treated with range-of-motion therapy. There were also no differences between the hips treated with a femoral varus osteotomy and those treated with an innominate osteotomy. Treatment did not have a significant effect on children who had a chronologic age of 8.0 years or less or a skeletal age of 6.0 years or less at the onset of the disease. In the lateral pillar B group and B/C border group, the outcomes of surgical treatment were significantly better than those of nonoperative treatment in children over the age of 8.0 years at the onset of the disease (p < or = 0.05). Patients who were 8.0 years old or less at the onset of the disease in lateral pillar group B did equally well with nonoperative and operative treatment. Hips in lateral pillar group C had the least favorable outcomes, with no differences between the operative and nonoperative groups. The lateral pillar classification (p < 0.0001) and the age at the onset of the disease (p = 0.0001) were both strong prognostic factors. Female patients did significantly worse than male patients if they were over the age of 8.0 years at the onset of the disease (p = 0.004). CONCLUSIONS The lateral pillar classification and age at the time of onset of the disease strongly correlate with outcome in patients with Legg-Calve-Perthes disease. Patients who are over the age of 8.0 years at the time of onset and have a hip in the lateral pillar B group or B/C border group have a better outcome with surgical treatment than they do with nonoperative treatment. Group-B hips in children who are less than 8.0 years of age at the time of onset have very favorable outcomes unrelated to treatment, whereas group-C hips in children of all ages frequently have poor outcomes, which also appear to be unrelated to treatment.

Pulmonary Function Following Early Thoracic Fusion in Non-Neuromuscular Scoliosis

BACKGROUND While early spinal fusion may halt progressive deformity in young children with scoliosis, it does not facilitate lung growth and, in certain children, it can result in thoracic insufficiency syndrome. The purpose of this study was to determine pulmonary function at intermediate-term follow-up in patients with scoliosis who underwent thoracic fusion before the age of nine years. METHODS Patients who had thoracic spine fusions before the age of nine years with a minimum five-year follow-up underwent pulmonary function testing. Forced vital capacity, forced expiratory volume in one second, and maximum inspiratory pressure were measured and compared with age-matched normal values. Patients with neuromuscular disease, skeletal dysplasias, or preexisting pulmonary disease were excluded, while those with rib malformations were included. The relationships between forced vital capacity and age at the time of surgery, length of follow-up, extent of the fusion, proximal level of the fusion, and revision surgery were studied. RESULTS Twenty-eight patients underwent evaluation. Twenty patients had congenital scoliosis, three had idiopathic scoliosis, three had scoliosis associated with neurofibromatosis, one had congenital kyphosis, and one had syndromic scoliosis. Seventeen patients had one spinal surgery, while eleven had additional procedures. The average age of the patients was 3.3 years at the time of surgery and 14.6 years at the time of follow-up. The average extent of the thoracic spine fused was 58.7%. The average forced vital capacity was 57.8% of age-matched normal values, and the average forced expiratory volume in one second was 54.7%. The forced vital capacity was <50% of normal in twelve of the twenty-eight patients, and two required respiratory support, implying that substantial restrictive lung disease was present. With the numbers studied, no significant correlation could be detected between the age at the time of fusion or the length of follow-up and pulmonary function. The extent of the spine fused correlated with the forced vital capacity (p = 0.01, r = -0.46). Fusions in the proximal aspect of the spine were found to be associated with diminished pulmonary function as eight of twelve patients with a proximal fusion level of T1 or T2 had a forced vital capacity of <50%, but only four of sixteen patients with a fusion beginning caudad to T2 had a forced vital capacity of <50% (p = 0.0004, r = 0.62). CONCLUSIONS Patients with proximal thoracic deformity who require fusion of more than four segments, especially those with rib anomalies, are at the highest risk for the development of restrictive pulmonary disease. Pulmonary function tests should be performed for all patients who have an early fusion. The pursuit of alternative procedures to treat early spinal deformity is merited.

Legg-Calve-Perthes disease. Part I: Classification of radiographs with use of the modified lateral pillar and Stulberg classifications.

BACKGROUND Accurate and reliable radiographic classifications of the relative severity and outcome of Legg-Calve-Perthes disease are essential in the study of that disease. As part of a prospective multicenter study, we sought to define more clearly the lateral pillar classification of severity and the Stulberg classification of outcome; we sought especially to define the borderlines between classification groups. METHODS We performed interobserver and intraobserver trials of the lateral pillar and Stulberg classifications using sets of twenty radiographs chosen from a prospective study of 345 hips. To establish reliable definitions of the lateral pillar classification, we added a new, intermediate group termed the B/C border group, which includes femoral heads with a thin or poorly ossified lateral pillar and those with a loss of exactly 50% of the original height of the lateral pillar. The resulting classification consists of four groups: A, B, B/C border, and C. In our application of the classification system of Stulberg et al., we defined a class-II femoral head as round and fitting within 2 mm of a circle on both anteroposterior and frog-leg lateral radiographs. We defined a Stulberg class-III femoral head as out of round by more than 2 mm on either view and a Stulberg class-IV femoral head as one with at least 1 cm of flattening of the weight-bearing articular surface. To assess interobserver and intraobserver agreement, we performed two trials of each classification with six orthopaedic surgeons reviewing twenty radiographs or pairs of radiographs. RESULTS In the first trial of the lateral pillar classification, there was 81% agreement per radiograph and the average weighted kappa was 0.71. In the second trial, there was 85% agreement per radiograph and the weighted kappa averaged 0.79. Intraobserver reliability testing showed a 77% match between Trials 1 and 2, an average weighted kappa of 0.81, and an average generalizability coefficient of 0.91. In Trial 1 of the Stulberg classification, there was 91% agreement per radiograph and an average weighted kappa of 0.82. In Trial 2, there was 92% agreement per radiograph and an average weighted kappa of 0.82. Intraobserver reliability testing showed an 89% match between Trials 1 and 2, an average weighted kappa value of 0.88, and an average generalizability coefficient of 0.92. CONCLUSIONS The interobserver and intraobserver trials of these classifications produced kappa values and generalizability coefficients in the excellent range. The modified lateral pillar classification and the redefined Stulberg classification are sufficiently reliable and accurate for use in studies of Legg-Calve-Perthes disease.

The Prevalence of Back Pain in Children Who Have Idiopathic Scoliosis

A retrospective study of 2442 patients who had idiopathic scoliosis was performed to determine the prevalence of back pain and its association with an underlying pathological condition. Five hundred and sixty (23 per cent) of the 2442 patients had back pain at the time of presentation, and an additional 210 (9 per cent) had back pain during the period of observation. There was a significant association between back pain and an age of more than fifteen years, skeletal maturity (a Risser sign of 2 or more), post-menarchal status, and a history of injury. There was no association with gender, family history of scoliosis, limb-length discrepancy, magnitude or type of curve, or spinal alignment. At the latest follow-up evaluation, 324 (58 per cent) of the 560 patients who had had back pain at presentation had no additional symptoms. Forty-eight (9 per cent) of the 560 patients who had back pain had an underlying pathological condition: twenty-nine patients had spondylolysis or spondylolisthesis, nine had Scheurmann kyphosis, five had a syrinx, two had a herniated disc, one had hydromyelia, one had a tethered cord, and one had an intraspinal tumor. A painful left thoracic curve or an abnormal neurological finding was most predictive of an underlying pathological condition, although only eight of the thirty-three patients who had such findings were found to have such a condition. When a patient with scoliosis has back pain, a careful history should be recorded, a thorough physical examination should be performed, and good-quality plain radiographs should be made. If this initial evaluation reveals normal findings, a diagnosis of idiopathic scoliosis can be made, the scoliosis can be treated appropriately, and non-operative treatment can be initiated for the back pain. It is not necessary to perform extensive diagnostic studies to evaluate every patient who has scoliosis and back pain.

A comparison between the Boston brace and the Charleston bending brace in adolescent idiopathic scoliosis

Study Design. The authors studied 319 patients with adolescent idiopathic scoliosis treated at the same institution with either a Boston brace or a Charleston bending brace. Objectives. To determine if both orthoses are equally effective in stopping curve progression and preventing the need for surgical correction. Summary of Background Data. Early reports suggest that the Charleston brace may be comparable to the Boston brace in its effectiveness and that both braces positively influence the natural history of idiopathic scoliosis. Methods. Skeletally immature (Risser 0, 1, or 2) patients with idiopathic scoliosis who were 10 years old or older at the time of brace prescription, had curves from 25° to 45°, and had no prior treatment were studied retrospectively. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Results. The Boston brace is more effective than the Charleston brace, both in preventing curve progression and in avoiding the need for surgery. These findings were most notable for patients with curves of 36°-45°, in whom 83% of the those treated with a Charleston brace had curve progression of more than 5°, compared with 43% of those treated with the Boston brace (p < 0.0001). Conclusion. When given the choice between these two orthoses in the treatment of adolescent idiopathic scoliosis, the authors recommend use of the Boston brace. The Charleston brace should be considered only in the treatment of smaller single thoracolumbar or single lumbar curves.

Dynamic External Fixation of Unstable Fractures of the Distal Part of the Radius. A Prospective, Randomized Comparison with Static External Fixation.

A prospective, randomized study was done to compare the results of dynamic external fixation (the Clyburn device) with those of static external fixation (the AO/ASIF device) in the treatment of fifty unstable fractures of the distal part of the radius. Mobilization of the wrist from neutral to 30 degrees of flexion was begun in the dynamic-fixator group at approximately two weeks, and full motion, allowing 30 degrees of extension, was started at approximately four weeks. The external fixation frames in both groups were kept in place for approximately ten weeks. Mobilization of the wrist in the dynamic-fixator group provided little gain in the mean motion of the wrist at the time of the removal of the fixator or at the one, six, or twelve-month evaluation. The static-fixator group had greater flexion of the wrist and radial deviation at the early and late follow-up examinations, while the dynamic-fixator group demonstrated only greater ulnar deviation one month after the fixator had been removed. Motion of the wrist in the dynamic-fixator group resulted in a statistically significant loss of radial length compared with that in the static-fixator group (four millimeters compared with one millimeter, p < 0.001). Complications were more frequent in the dynamic-fixator group. As evaluated with a modification of the scoring system of Gartland and Werley, 92 percent of the results at one year were excellent or good in the static-fixator group and 76 percent, in the dynamic-fixator group. The results of this study cannot support the concept of early mobilization with a dynamic external fixator for the treatment of unstable fractures of the distal part of the radius.

Maturity assessment and curve progression in girls with idiopathic scoliosis.

BACKGROUND Scoliosis progression during adolescence is closely related to patient maturity. Maturity has various indicators, including chronological age, height and weight changes, and skeletal and sexual maturation. It is not certain which of these indicators correlates most strongly with scoliosis progression. The purpose of the present study was to evaluate various maturity measurements and how they relate to scoliosis progression. METHODS Physically immature girls with idiopathic scoliosis were evaluated every six months through their growth spurt with serial spinal radiographs; hand skeletal ages; Oxford pelvic scores; Risser sign determinations; height; weight; sexual staging; and serologic studies of the levels of selected growth factors, estradiol, bone-specific alkaline phosphatase, and osteocalcin. These measurements were then correlated with the curve-acceleration phase. RESULTS The period and pattern of curve acceleration began during Risser stage 0 for all patients. Skeletal maturation scores derived with the use of the Tanner-Whitehouse-III RUS method, particularly those for the metacarpals and phalanges, were superior to all other indicators of maturity. Regression of the scores provided good estimates of maturity relative to the period of curve progression (Pearson r = 0.93). The initiation of this period occurred simultaneously with digital changes from Tanner-Whitehouse-III stage F to G. At this stage, curves also separated into rapid, moderate, and low-acceleration patterns, with specific curve types in the rapid and moderate-acceleration groups. The low-acceleration group was not confined to a specific curve type. CONCLUSIONS The curve-acceleration phase separates curves into various types of curve progression. The Tanner-Whitehouse-III RUS scores are highly correlated with timing relative to the curve-acceleration phase and provide better maturity determination and prognosis determination during adolescence than the other parameters tested. Accurate skeletal maturity determination should be used as the primary maturity measurement in girls with idiopathic scoliosis.

CHD7 gene polymorphisms are associated with susceptibility to idiopathic scoliosis

Idiopathic scoliosis (IS) is the most common spinal deformity in children, and its etiology is unknown. To refine the search for genes underlying IS susceptibility, we ascertained a new cohort of 52 families and conducted a follow-up study of genomewide scans that produced evidence of linkage and association with 8q12 loci (multipoint LOD 2.77; P=.0028). Further fine mapping in the region revealed significant evidence of disease-associated haplotypes (P<1.0 x 10-4) centering over exons 2-4 of the CHD7 gene associated with the CHARGE (coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness) syndrome of multiple developmental anomalies. Resequencing CHD7 exons and conserved intronic sequence blocks excluded coding changes but revealed at least one potentially functional polymorphism that is overtransmitted (P=.005) to affected offspring and predicts disruption of a caudal-type (cdx) transcription-factor binding site. Our results identify the first gene associated with IS susceptibility and suggest etiological overlap between the rare, early-onset CHARGE syndrome and common, later-onset IS.