Pediatric calcaneal fractures.

Calcaneal fractures in pediatric patients are seen infrequently. We retrospectively reviewed 22 skeletally immature patients with 23 fractures of the calcaneus before their distal tibial physis had fused. Eighteen (78%) of these fractures were intraarticular and five (22%) were extraarticular. Nine patients were followed for an average of 4.4 years. Of these nine fractures, 8 were treated non-operatively and one was treated with open reduction and internal fixation. A modification of the American Orthopaedic Foot and Ankle Society scoring system, which focuses on residual complaints of pain, work or sports restrictions, ability to walk on different surfaces and gait abnormalities, was employed to assess their outcome. Seven of the nine patients were free of pain, had unrestricted foot function, and possessed no apparent gait abnormalities. Two patients had activity related and cold weather related pain. We believe that the excellent prognosis for both intraarticular and extraarticular fractures, seen in this study is multi-fold. First, the immature talus and calcaneus have a superior capacity to remodel. Second, pediatric calcaneal fractures are usually consequence of low energy trauma. Lastly, a favorable intraarticular fracture pattern, unique to the skeletally immature calcaneus may exist, rendering a good prognosis.

Structures and comparison of the Y98H (2.0 A) and Y98W (1.5 A) mutants of flavodoxin (Desulfovibrio vulgaris).

The structures for two mutants at the Tyr98 site of Desulfovibrio vulgaris flavodoxin have been determined. The first, a tyrosine-to-histidine (Y98H) variant, was determined at the moderately high resolution of 2.0 A, while the tyrosine-to-tryptophan variant (Y98W) yielded very high resolution data (beyond 1.5 A) allowing a detailed look at the water structure, alternate side-chain conformations and the planarity of the FMN. Both structures were solved by molecular replacement beginning with the native (P2A) coordinates as a starting point. The Y98H variant of D. vulgaris flavodoxin crystallizes in space group P2(1)2(1)2(1), with unit-cell parameters a = 41.96, b = 61.45, c = 57.04 A, while the Y98W mutant adopts space group P2(1), with a = 41.29, b = 55.82, c = 32.52 A, beta = 100.68 degrees. Refinement for both mutants utilized PROLSQ followed by, for the high-resolution Y98W structure, anisotropic refinement as implemented in SHELXL. Final R factors of 17% for the Y98H mutant and 9.8% for the Y98W mutant were obtained. For the high-resolution (1.5 A) Y98W mutant, 31,010 unique reflections were collected from a single crystal. The final model includes 273 solvent molecules, with eight side chains assuming multiple conformations. At this resolution, the detailed conformation of the FMN can be observed, with both a bow and twist being noted. A comparison is made between the two mutants and the different oxidation states of the native flavodoxin. Although both mutants show similar E(2) (oxidized/semiquinone) one-electron redox potentials to the native, the E(1) (semiquinone/hydroquinone) redox potential for the Y98H mutant is significantly different from that of the Y98W variant and the native protein. The surprising similarity in the folding of the polypeptide chain 60--64 between the two mutants and the reduced states of the native is discussed. The interaction between O61 and N5 in the flavin is discussed because of the new conformation of this loop.

Biomechanical analysis of compression screw fixation versus standard in situ pinning in slipped capital femoral epiphysis.

A slipped capital femoral epiphysis was created in 12 matched pairs of immature bovine femora using an anterior-to-posterior-directed shear force. All soft tissues, with the exception of the perichondrial ring, were removed before testing. One specimen from each pair was fixed with a single cannulated screw in standard fashion, whereas the contralateral specimen was fixed with a single screw that compressed the physis. The amount of compression achieved was quantified using Fuji film. Standard fixation yielded 1.4 MPa of pressure across the physis; compression fixation yielded 3.2 MPa, a 2.3-fold difference (p = 0.0001). The compression fixation was 47% more stiff than standard technique (p = 0.030), yet the differences in ultimate strength (p = 0.180) and energy absorbed at failure (p = 0.910) were not statistically significant. The stiffness of the compressed specimens remained less than that of the intact femora. Single-screw compression fixation of in vitro bovine femora was significantly more stiff than the current, widely used noncompression fixation technique, yet does not compromise the ultimate strength, energy absorbed, or the technical ease of single-implant fixation.

Titanium elastic nails for pediatric femur fractures: a multicenter study of early results with analysis of complications.

Titanium elastic nailing is used instead of traction and casting in many European centers, but limited availability has prevented widespread use in North America. Before a planned general release in America, titanium elastic nails (TENs) were trialed at several major pediatric trauma centers. This multicenter study is a critical analysis of early results and complications of the initial experience. Overall, TENs allowed rapid mobilization with few complications. The results were excellent or satisfactory in 57 of the 58 cases. No child lost rotational alignment in the postoperative period. Irritation of the soft tissue near the knee by the nail tip occurred in four patients, leading to a deeper infection in two cases. As indications, implantation technique, and aftercare are refined, TENs may prove to be the ideal implant to stabilize many pediatric femur fractures, avoiding the prolonged immobilization and complications of traction and spica casting.

A fluorescence-based method for determining the surface coverage and hybridization efficiency of thiol-capped oligonucleotides bound to gold thin films and nanoparticles.

Using a fluorescence-based method, we have determined the number of thiol-derivatized single-stranded oligonucleotides bound to gold nanoparticles and their extent of hybridization with complementary oligonucleotides in solution. Oligonucleotide surface coverages of hexanethiol 12-mer oligonucleotides on gold nanoparticles (34 +/- 1 pmol/cm2) were significantly higher than on planar gold thin films (18 +/- 3 pmol/cm2), while the percentage of hybridizable strands on the gold nanoparticles (1.3 +/- 0.3 pmol/cm2, 4%) was lower than for gold thin films (6 +/- 2 pmol/cm2, 33%). A gradual increase in electrolyte concentration over the course of oligonucleotide deposition significantly increases surface coverage and consequently particle stability. In addition, oligonucleotide spacer sequences improve the hybridization efficiency of oligonucleotide-modified nanoparticles from approximately 4 to 44%. The surface coverage of recognition strands can be tailored using coadsorbed diluent oligonucleotides. This provides a means of indirectly controlling the average number of hybridized strands per nanoparticle. The work presented here has important implications with regard to understanding interactions between modified oligonucleotides and metal nanoparticles, as well as optimizing the sensitivity of gold nanoparticle-based oligonucleotide detection methods.

Variability in gait analysis interpretation.

The purpose of this study was to assess the reliability of interpretation of gait analysis data between physicians and institutions. Gait analysis data from seven patients were reviewed by 12 experienced gait laboratory physicians from six institutions. Reviewers identified problems and made treatment recommendations based on the data provided. Agreement among physicians for the most commonly diagnosed problems was slight to moderate (kappa range, 0.14-0.46). Physicians agreed on identification of soft tissue more than bony problems (intraclass correlation, 0.56 vs. 0.37). Variability regarding surgical recommendations for soft-tissue procedures (kappa range, 0.20-0.64) was similar to that for diagnosis of both soft-tissue and bone problems, although recommendation for hamstring lengthening showed substantial agreement (kappa = 0.64). There was less agreement in recommendation of osteotomies (kappa range, 0.13-0.22). Physicians agreed more on the number of soft-tissue procedures than bone procedures recommended (intraclass correlation, 0.65 vs. 0.19). There was an interinstitutional difference in the frequency of soft-tissue (p = 0.0152) and osseous problem identification (p = 0.0002), as well as in the frequency of recommendations for soft-tissue surgery (p = 0.0004) and osteotomies (p < 0.0001). Although gait analysis data are themselves objective, this study demonstrates some subjectivity in their interpretation. The interobserver variability reported here is similar to that reported for established classification systems of various orthopedic conditions.

A technique to determine proper pin placement of crossed pins in supracondylar fractures of the elbow.

Supracondylar humerus fractures are the most common elbow injury in children. Stable fractures can be closed, reduced, and casted, whereas unstable fractures require percutaneous pinning. Studies have shown that there is a biomechanical advantage of crossed pin fixation as opposed to two lateral pin fixation. However, medial pin placement has the risk of injuring the ulnar nerve. This modification of technique was used on 46 patients, aged 12 months to 14 years (median age, 3.6 years). Two patients had an ulnar sensory and motor neurapraxia, and two patients had cubitus varus deformities postoperatively. Thus, a safe, easy, and reproducible technique of crossed pin fixation is described here.

The effect of preoperative gait analysis on orthopaedic decision making.

The impact of preoperative gait analysis on the orthopaedic care of 97 patients (101 gait analyses) at the authors' institution was evaluated. For the 70 patients for whom a specific treatment plan had been outlined before the preoperative gait study, the treatment plan was altered in 62 (89%) after the gait analysis study. In 10 of the 70 patients with specific treatment plans before the gait study, the referring physician also served as the physician in the gait laboratory; ultimate treatment was changed in nine of these 10 patients. Of the 273 surgical procedures recommended before the gait study in the 70 patients, 106 (39%) of these procedures were not done when the gait laboratory data were considered. An average of 1.5 procedures per patient that were planned before the gait study ultimately were not deemed necessary by the treating physician after the addition of the gait data. An additional 110 procedures (1.6 per patient) that had not been recommended before the gait study ultimately were performed after addition of the gait laboratory data. This study shows that ultimate surgical intervention frequently is altered by the addition of gait laboratory data.

Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle.

Cdc25B is a dual specificity phosphatase involved in the control of cyclin-dependent kinases and the progression of cells through the cell cycle. A series of minimal domain Cdc25B constructs maintaining catalytic activity have been expressed. The structure of a minimum domain construct binding sulfate was determined at 1.9 A resolution and a temperature of 100 K. Other forms of the same co?nstruct were determined at lower resolution and room temperature. The overall folding and structure of the domain is similar to that found for Cdc25A. An important difference between the two is that the Cdc25B domain binds oxyanions in the catalytic site while that of Cdc25A appears unable to bind oxyanions. There are also important conformational differences in the C-terminal region. In Cdc25B, both sulfate and tungstate anions are shown to bind in the catalytic site containing the signature motif (HCxxxxxR) in a conformation similar to that of other protein tyrosine phosphatases and dual specificity phosphatases, with the exception of the Cdc25A. The Cdc25B constructs, with various truncations of the C-terminal residues, are shown to have potent catalytic activity. When cut back to the site at which the Cdc25A structure begins to deviate from the Cdc25B structure, the activity is considerably less. There is a pocket extending from the catalytic site to an anion-binding site containing a chloride about 14 A away. The catalytic cysteine residue, Cys473, can be oxidized to form a disulfide linkage to Cys426. A readily modifiable cysteine residue, Cys484, resides in another pocket that binds a sulfate but not in the signature motif conformation. This region of the structure is highly conserved between the Cdc25 molecules and could serve some unknown function.

Outcome of hamstring lengthening and distal rectus femoris transfer surgery.

To evaluate the outcome of hamstring lengthening and distal rectus femoris transfer, a retrospective study was performed comparing preoperative and postoperative gait analysis data from 16 children with neurologic involvement. Postoperatively, the timing of peak knee flexion during swing and the total arc of knee motion significantly improved. Hamstring range of motion and knee extension at terminal swing significantly improved, but stride length and gait velocity did not for the overall population. Patients who used braces postoperatively showed an improvement in stride length and velocity when wearing orthoses. This suggests that postoperative bracing may be needed in some patients to maximize the surgical outcome.

Diagnosis and treatment of slipped capital femoral epiphysis.

Slipped capital femoral epiphysis remains a diagnostic problem despite numerous papers written on the subject. The most important factor in the diagnosis of slipped capital femoral epiphysis is suspicion by the practitioner. The history, physical examination, and radiographic imaging are important in the confirmation of the diagnosis. Imaging is the topic of 1998 with advances in the areas of ultrasound. Ultrasound may be better in experienced hands than plain radiography in the diagnosis of slipped capital femoral epiphysis. Magnetic resonance imaging is used for diagnosis of slipped capital femoral epiphysis and in the assessment of pre-slips. The magnetic resonance image can be oriented to a plane orthoganol to the plane of the physis to assess the width of the physis and to detect edema in the area of the physis.

Variability in measurement of acetabular index in normal and dysplastic hips, before and after reduction.

This study examined the variability in the measurement of the acetabular index (AI) in normal and dysplastic hips, both before and after reduction. This variability for dysplastic hips is greater than that of normal hips. The variability is greater before an open or closed reduction than after reduction, and the variability after an open reduction is nearly 3 times greater than after a closed reduction. The 95% confidence interval of the AI is 10.1 degrees intraobserver and 21.9 degrees interobserver for all hips. The AI is most accurate in the situation in which it is most useful, after a closed reduction of a dysplastic hip. A 95% confidence interval of 5.1 degrees in this selected population supports the use of the AI for monitoring acetabular remodeling after closed reductions in accordance with previous clinical recommendations.

The carpal stretch test.

OBJECTIVE: To compare the sensitivity of traditional motion studies, bone scintigraphy and radiocarpal arthrography to a "carpal stretch test," for evaluation of dynamic dissociative carpal instability. DESIGN: Experimental study comparing the results of the tests to the findings of arthroscopy, the "gold standard." SETTING: A university hospital-based upper extremity practice. PATIENTS: Six patients with chronic wrist pain, arthroscopically confirmed proximal row ligamentous disruption and radiographs not suggestive of proximal row instability. INTERVENTIONS: The carpal stretch test: both affected and unaffected wrists were subjected to the same testing, wherein the wrist was suspended from finger traps for 10 minutes by a 4.5-kg weight. Standardized posteroanterior radiographs were taken of the suspended wrists. MAIN OUTCOME MEASURES: Disruption of Gilula's arcs I and II, and sensitivity of the carpal stretch test compared with other investigations. MAIN RESULTS: Step deformities ranging from 2.5 to 6 mm (average 3.7 mm) were recorded in the affected wrists and 0 to 4 mm (average 1.5 mm) in the "unaffected" wrists. The test was more sensitive than traditional radiography, arthrography and scintigraphy in defining both presence and site of proximal carpal row ligamentous tears and was almost as sensitive as arthroscopy. CONCLUSION: In patients with chronic wrist pain and dynamic dissociative wrist instability, the carpal stretch test may prove to be a valuable screening tool for detecting ligamentous tears of the proximal carpal row.

Psoas over the brim lengthenings. Anatomic investigation and surgical technique.

Lengthening of the psoas tendon commonly is performed for various conditions of the hip including developmental dysplasia and neuromuscular contractures and instability. Anecdotal reports of injury to surrounding neurovascular structures suggest an investigation of the local anatomy is warranted. Using magnetic resonance images from 54 children younger than 10 years, the authors examined the anatomic relationship between major neurovascular structures (femoral artery and vein, external iliac artery and vein, femoral nerve) and the psoas tendon. The mean distance between the neurovascular structures and the psoas tendon in the over the brim position is 1 cm, although it may be as close as 4 mm in a child. The mean distance is 3.1 cm at the tendon's insertion at the lesser trochanter. Surgeons performing psoas over the brim lengthenings should be aware that major neurovascular structures may be only 4 mm from the psoas tendon. The recommended surgical technique is presented.

Sugar nucleotide concentrations in red blood cells of patients on protein- and lactose-limited diets: effect of galactose supplementation.

Uridine diphosphate (UDP) galactose, a pivotal compound in the metabolism of galactose, is the obligate donor of galactose in the formation of complex glycoconjugates. The cellular UDPgalactose concentration has been thought to be maintained by the interconversion of UDPglucose and UDPgalactose by UDPgalactose-4-epimerase. However, recent findings of lower average red blood cell (RBC) UDPgalactose concentrations in galactose-1-phosphate uridyltransferase-deficient patients suggest that other factors play a role in determining its concentration. To test the hypothesis that the amount of galactose traversing the Leloir pathway contributes to the cellular UDPgalactose pool, we determined RBC UDPgalactose in patients with maple syrup urine disease (MSUD), phenylketonuria (PKU), and other metabolic diseases who were treated with a low-protein, and consequently, low-lactose diet. Six patients with MSUD were also supplemented with 19 g galactose/d and their UDPhexose concentrations were measured at intervals. We show that young patients with MSUD or PKU have decreased average RBC UDPgalactose concentrations when compared with similarly aged healthy subjects. Galactose supplementation of MSUD patients significantly increased their UDPgalactose concentrations in both RBCs and white blood cells (WBCs) from 29.5 +/- 1.5 to 42.3 +/- 5.8 nmol/g hemoglobin and from 69.0 +/- 7.5 to 193.0 +/- 49.0 nmol/g protein, respectively. Discontinuation of supplementation was associated with a return to basal values in RBCs and a reattainment of the pretreatment ratio of UDPglucose to UDPgalactose in WBCs. These observations demonstrate that dietary galactose is a factor in establishing the steady state concentrations of the uridine sugar nucleotides and imply that galactose metabolism modulates the achievement of an epimerase-mediated equilibrium.

Osteopenia in children: CT assessment.

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

Effect of glucose and galactose loading in normal subjects on red and white blood cell uridine diphosphate sugars.

In order to test the assumption that red blood cell (RBC) uridine diphosphate galactose content is regulated in part by dietary galactose and to help comprehend factors influencing RBC and white blood cell (WBC) uridine diphosphate hexose concentrations in vivo, oral loading studies were performed with 50 g of galactose or 75 g of glucose in normal adults. While elevations of blood glucose did not influence RBC or WBC UDPhexose levels, increased blood galactose concentrations caused transient increases in both RBC and WBC UDPgalactose. In both RBC and WBC, the UDPgalactose-4-epimerase was rate limiting. In comparison to RBC, WBC had larger changes in UDPgalactose levels, synthesized additional UDPglucose through the action of UDPglucose pyrophosphorylase and began to restore the equilibrium ratio between UDPglucose and UDPgalactose concentrations while the plasma galactose level was still increasing. Thus, galactose ingestion alters the steady-state levels of UDPhexoses in circulating cells. The modulation of UDPglucose and UDPgalactose concentrations, occurring after the presentation of galactose to cells, as a result of the combined actions of GALT and UDPgalactose-4-epimerase, may be important in determining rates of synthesis of complex glycoconjugates.

Comparison of erythrocyte uridine sugar nucleotide levels in normals, classic galactosemics, and patients with other metabolic disorders.

By limiting galactosylation mechanisms, a cellular deficiency of the uridine sugar nucleotide, UDPgalactose, has been implicated as a cause of the long-term complications seen in patients with classic galactosemia despite dietary treatment. As a result, great interest has been generated in the accurate assessment of UDPgalactose, as well as UDPglucose, from which UDPgalactose may be derived by the function of a ubiquitous, active UDPgalactose-4-epimerase. Since several series of values for the concentration of these compounds in red blood cells (RBCs) of galactosemics have been flawed by the use of methods subsequently shown to be unsuitable, we have quantified erythrocyte UDPgalactose and UDPglucose levels by an accurate high-performance liquid chromatography (HPLC) assay in 116 normals, 76 galactosemics, and 39 patients with other metabolic disorders. These large groups have permitted the evaluation of age, diet, and genotype as influential factors in the steady-state RBC levels of the sugar nucleotides. The data show that age is an important determinant of RBC levels, with children younger than 10 years having higher values than individuals older than 10 years. Mean UDPgalactose levels in galactosemic children younger than 10 years and those older than 10 years were 30% and 18% lower, respectively, than levels in comparable normals. Although the mean differences were highly significant, there was considerable overlap of individual values. There was no difference in UDPglucose levels between galactosemics and normals.(ABSTRACT TRUNCATED AT 250 WORDS)

Uridine diphosphate hexoses in leukocytes and fibroblasts of classic galactosemics and patients with other metabolic diseases.

To examine uridine diphosphate hexose (UDPhexose) content of cells that have more complete metabolic patterns than erythrocytes, which have been commonly used in the study of galactosemia, the concentrations of uridine diphosphate galactose (UDPgalactose) and uridine diphosphate glucose (UDPglucose) were determined in white blood cells (WBC) and fibroblasts cultured from skin biopsies. Leukocyte UDPgalactose and UDPglucose values were determined in 60 normal individuals, 14 classic galactosemics, and 18 patients with other metabolic diseases on protein-restricted and low-lactose diets. There was no difference in the average concentration of these compounds between any of these groups. There was no relationship between age and WBC UDPhexose content or correlation of WBC and erythrocyte UDPhexose levels in the same blood specimens. WBC from galactosemic individuals differ from their red blood cells because the former do not show the low average UDPgalactose levels and abnormal UDPglucose to UDPgalactose ratio previously reported for erythrocytes from galactose-1-phosphate uridyltransferase-deficient individuals. Fibroblast cell lines from 10 normal and 10 galactosemic individuals, cultured and grown to confluence in glucose medium, also showed no difference in nucleotide sugar concentrations. Thus far, of the cell types easily available, red blood cells appear to be unique in showing an abnormality in nucleotide sugar metabolism. The fact that galactosemic fibroblasts demonstrate no abnormality in the concentration of these compounds suggests that the defective galactosylation that has been observed in galactosemic fibroblasts is not due to unavailability of UDPgalactose.

Uridine diphosphoglucose content of human erythrocytes: assessment by conversion to uridine diphosphoglucuronate.

To settle the ongoing controversy regarding differential uridine diphosphoglucose (UDPG) and uridine diphosphogalactose (UDPGal) content of erythrocytes, which may be important in evaluating the metabolic abnormality in patients with galactosemia, we derived a combined enzymatic-high-performance liquid chromatography (HPLC) assay. Uridine diphosphoglucuronate (UDPGA), the unique product of UDPG dehydrogenase activity, was separated and quantified by HPLC in extracts of human erythrocytes. The quantity of UDPGA produced in cell filtrates incubated with the enzyme corresponds to the amount of UDPG directly determined by HPLC. The amount of UDPGA produced was independent of the enzyme purity or activity used. On the other hand, the amounts of UDPG estimated by fluorometric measurement of the production of reduced nicotinamide adenine dinucleotide varied with the enzyme purity and activity. The combined enzymatic-HPLC method confirms the direct determinations of UDPG content of normal erythrocytes. The results indicate that, under appropriate conditions, the fluorometric-based assay will give accurate estimates of UDPG, but the direct HPLC method yields consistent and correct UDPG and UDPGal determinations.