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Biomedical subjects

V T Tolo

Publications and source records attributed to V T Tolo.

At least 19 recordsLinked to original sources

Radiographic findings and Gs-alpha bioactivity studies and mutation screening in acrodysostosis indicate a different etiology from pseudohypoparathyroidism.

Acrodysostosis is an uncommon skeletal dysplasia associated with nasal hypoplasia, midface deficiency, severe brachydactyly, and varying degrees of hearing loss and mental retardation. Previous publications have suggested that it may be difficult to distinguish acrodystostosis from pseudohypoparathyroidism on clinical grounds, but acrodysostosis does appear to have distinct clinical and radiologic findings. Spinal stenosis is an underappreciated risk in acrodysostosis, despite the reported loss of normal caudal widening of the lumbar interpediculate distance on AP spine radiographs in the original report of this disorder by Robinow et al., with confirmation of these radiographic findings by Butler et al. We report two sporadic cases of acrodysostosis, one of which required decompressive laminectomy for symptomatic spinal stenosis, and review 11 cases of acrodysostosis from 9 families that were submitted to the International Skeletal Dysplasia Registry. The objective of this report is to determine the frequency and severity of spinal stenosis in patients with acrodysostosis and to summarize the clinical and radiographic findings of acrodysostosis in an effort to distinguish acrodysostosis clearly from pseudohypoparathyroidism. The pattern of brachydactyly differs between these two conditions, and varying degrees of spinal stenosis are characteristic of acrodysostosis. Both our index patients with acrodysostosis had normal bioactivity of the alpha subunit of the Gs protein, therefore indicating that acrodysostosis has a different pathogenesis from pseudohypoparathyroidism. Furthermore, single-strand confirmational polymorphism (SSCP) analysis failed to demonstrate any confirmational alterations in the coding exons of the Gs alpha gene. These radiographic and laboratory findings substantiate that acrodysostosis is clinically different from pseudohypoparathyroidism and that it is necessary to follow patients with acrodysostosis for signs of spinal stenosis.

Dysostoses↗

Operative treatment of supracondylar fractures of the humerus in children. The consequences of pin placement.

BACKGROUND: The commonly accepted treatment of displaced supracondylar fractures of the humerus in children is fracture reduction and percutaneous pin fixation; however, there is controversy about the optimal placement of the pins. A crossed-pin configuration is believed to be mechanically more stable than lateral pins alone; however, the ulnar nerve can be injured with the use of a medial pin. It has not been proved that the added stability of a medial pin is clinically necessary since, in young children, pin fixation is always augmented with immobilization in a splint or cast. METHODS: We retrospectively reviewed the results of reduction and Kirschner wire fixation of 345 extension-type supracondylar fractures in children. Maintenance of fracture reduction and evidence of ulnar nerve injury were evaluated in relation to pin configuration and fracture pattern. Of 141 children who had a Gartland type-2 fracture (a partially intact posterior cortex), seventy-four were treated with lateral pins only and sixty-seven were treated with crossed pins. Of 204 children who had a Gartland type-3 (unstable) fracture, fifty-one were treated with lateral pins only and 153 were treated with crossed pins. RESULTS: There was no difference with regard to maintenance of fracture reduction, as seen on anteroposterior and lateral radiographs, between the crossed pins and the lateral pins. The configuration of the pins did not affect the maintenance of reduction of either the Gartland type-2 fractures or the Gartland type-3 fractures. Ulnar nerve injury was not seen in the 125 patients in whom only lateral pins were used. The use of a medial pin was associated with ulnar nerve injury in 4% (six) of 149 patients in whom the pin was applied without hyperflexion of the elbow and in 15% (eleven) of seventy-one in whom the medial pin was applied with the elbow hyperflexed. Two years after the pinning, one of the seventeen children with ulnar nerve injury had persistent motor weakness and a sensory deficit. CONCLUSIONS: Fixation with only lateral pins is safe and effective for both Gartland type-2 and Gartland type-3 (unstable) supracondylar fractures of the humerus in children. The use of only lateral pins prevents iatrogenic injury to the ulnar nerve. On the basis of our findings, we do not recommend the routine use of crossed pins in the treatment of supracondylar fractures of the humerus in children. If a medial pin is used, the elbow should not be hyperflexed during its insertion.

Bone Nails↗

Complications of posterior iliac crest bone grafting in spine surgery in children.

STUDY DESIGN: The perioperative and postoperative complications associated with harvesting posterior iliac crest bone graft in children were reviewed. A retrospective study was performed and a questionnaire interview conducted. OBJECTIVES: To determine the morbidity associated with posterior iliac crest bone graft in children. SUMMARY OF BACKGROUND DATA: Iliac crest bone is commonly used as a source of bone graft in spine surgery. Although there are multiple reports of complications in adults, there are no reports in children. METHODS: A retrospective chart review was performed of 214 consecutive children who underwent spinal fusion with posterior iliac crest bone graft from 1990 through 1996. An interview was conducted of 87 patients with normal mental status, predominantly those with idiopathic scoliosis with a minimum of 2 years' follow-up (mean, 55 months). RESULTS: The review showed one (0.5%) instance of arterial injury in the sciatic notch. Two (1%) patients had infections, both of which resolved with a single irrigation and débridement. There was one documented instance of sacroiliac penetration that did not cause clinical problems. The chart review showed three (1.4%) instances of continued pain and one (0.5%) of numbness. By contrast to the few reports of pain in the chart review, responses to an interview of 87 patients showed 21 (24%) children reporting pain at the iliac crest site, with 13 (15%) reporting problems with daily activities. The self-reported pain, on a scale of 1 to 10, ranged from 1 to 10 with a mean of 4. Nonsteroidal anti-inflammatory drugs (NSAIDS) were taken by eight (9%) children for pain at the bone graft site. Five (6%) reported skin irritation, and 18 (20%) mentioned numbness surrounding the scar. CONCLUSION: The perioperative rate of complications in iliac crest bone grafting in children is low (2%). The complication of pain (24%) and pain that is severe enough to interfere with daily activity (15%) is significant at a mean follow-up of more than 4 years. The true extent of pain and numbness after posterior iliac crest bone grafting in children was severely underreported in the medical records and may be underrecognized.

Adolescent↗

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.

Adolescent↗

Impact of postoperative gait analysis on orthopaedic care.

The impact of postoperative gait analysis on the ongoing orthopaedic care of 38 consecutive patients with a static encephalopathy was evaluated. Of the 38 postoperative gait analyses, 32 (84%) resulted in recommendations of a change in patient care. Surgery was recommended in 16 of 38 (42%) cases, bracing in 20 (53%) cases, and specific physical therapy regimens in eight (21%) cases. Eleven of the 38 (29%) patients had changes recommended in at least two of the three areas (surgery, bracing, and therapy). The results of this study suggest that postoperative gait analysis serves not only as a measure of treatment outcome, but also as a useful tool in planning ongoing care for these patients.

Brain Injuries↗

A simplified valgus osteotomy of the proximal femur in children.

Valgus osteotomy of the hip is required in a number of orthopedic conditions in children. We present a simplified valgus osteotomy in which a dynamic compression plate is used. This technique has the advantages of using easily available equipment, requiring only one osteotomy, and providing immediate rigid fixation while not violating the proximal femoral physis. We have used this simplified technique for valgus osteotomy in six hips in four children with excellent fixation, good maintenance of correction, and no complications.

Child↗

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.

Adolescent↗

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.

Cadaver↗

Soleus neurectomy for dynamic ankle equinus in children with cerebral palsy.

Problems with the gastrocnemius-soleus muscle group can severely impair the gait of children with cerebral palsy. Treatments, including bracing, muscle lengthening, neurectomy, or a combination, have been used with mixed results. Soleus neurectomy was performed as the primary treatment for ankle clonus in 38 legs of 21 children with a variety of cerebral palsies. Concurrent heel cord or muscle lengthening was performed if needed. Patients were followed for an average of 9 years (range, 2 to 14 years). Clonus recurred in 4 treated ankles. In 2 cases, this was due to a nerve anomaly. Postneurectomy Achilles tendon lengthening was required in 8 of the treated ankles. Neurectomy was beneficial for 19 of 21 children. Functional improvements included better control of stopping, better balance, and less toe walking. The greatest improvement was seen in those patients who did not also have heel cord contractures.

Achilles Tendon↗

Congenital dislocation of the hip.

Neonatal hip dysplasia remains a difficult condition to diagnose and treat. Early periodic infant hip examination is the primary screening tool, but subtle hip instabilities can go undetected until fixed dislocations are discovered when the child begins to walk. Early nonoperative intervention in the neonatal period is usually effective using a Pavlik-type harness. For infants in whom this disorder is discovered after walking age, surgery is often needed to successfully reduce the hip. Radiographic evaluation of neonatal hip dysplasia is often difficult, but the evolving use of ultrasound, computed tomography, and magnetic resonance imaging is making this easier. The role of ultrasound as a primary screening device in the United States remains to be defined.

Hip Dislocation, Congenital↗

Immunocytochemical detection of cyclin A and cyclin D in formalin-fixed, paraffin-embedded tissues: novel, pertinent markers of cell proliferation.

Cyclin proteins in association with cyclin-dependent protein kinase subunits represent a new class of potentially oncogenic serine/threonine protein kinases that function to execute critical cell cycle transitions in all eukaryotic cells. Characterized by dramatic fluctuations in abundance, which occur in accordance with the periodicity of the cell cycle, the expression patterns of specific cyclins provide a unique and relevant indicator of cellular activation and cell cycle progression. In this study, we introduce a series of monospecific antibodies that are selective for human cyclin A and cyclin D, respectively, and we assess the feasibility of utilizing these reagents for immunocytochemical analyses. Conditions were optimized for detecting cyclin A and cyclin D in formalin-fixed, paraffin-embedded sections of the postnatal human palatine tonsil, in which normal cell proliferation is well characterized. Subsequent studies demonstrated the performance of these antibodies in the examination of pediatric bone tumors, in which decalcification methods are additionally performed. In both cases, the proliferative status of individual cells was monitored with an exceedingly high degree of resolution. Taken together with the available biochemical data, the results of these studies reveal a novel means of characterizing the proliferative status of normal as well as neoplastic tissues. The demonstrated utility of these immunochemical reagents will potentially facilitate retrospective studies aimed at examining cell proliferation in a wide variety of archival histopathologic specimens.

Antibodies↗

Molecular cloning of the human CAK1 gene encoding a cyclin-dependent kinase-activating kinase.

Cyclin-dependent, proline-directed protein kinases normally function to execute critical cell cycle transitions; abnormal expression and/or viral subversion of the positive (cyclins) and negative (Pic1) regulatory subunits may contribute to neoplastic transformation and tumorigenesis. In addition to the binding of regulatory subunits, the enzymatic activities of the cyclin-dependent kinases, Cdc2 and Cdk2, are tightly regulated by site-specific protein phosphorylation events. Recent studies have identified a critical phosphorylation site (Thr-161) located within kinase Subdomain VIII that is necessary for Cdc2 activation, and enzymatic activities capable of carrying out this heterologous phosphorylation event have been detected in both Xenopus oocytes and human somatic cells. In this report, we characterize by molecular cloning a human homologue of the Xenopus Cdk-activating kinase (Cak, encoded by MO15); the novel human gene is designated (HS)CAK1. While only 75% identity is observed at the nucleotide level, the deduced amino acid sequence encoded by (HS)CAK1 is approximately 87% identical to that of the Xenopus MO15 gene in corresponding regions. The catalytic domain of (HS)Cak1, defined by conserved kinase Subdomains I through XI, exhibits considerable homology with (HS)Cdc2, suggesting that this kinase cascade involves closely related enzymes. Immunological studies with anti-Cak antibodies confirm the presence of specific immunoreactivity in highly purified preparations of the human Cdc2-activating kinase. The molecular characterization of (HS)CAK1 should facilitate studies of its physiological regulation, as well as its potential utility as a target for therapeutic intervention in the treatment of proliferative disorders.

Amino Acid Sequence↗

Outcome of Wisconsin instrumentation in idiopathic scoliosis. Minimum 5-year follow-up.

Wisconsin segmental spinal instrumentation was developed by Drummond et al to provide rigid fixation for correction of spinal deformities without the risk of neurologic injury associated with the passage of sublaminar wires. Up to this point, there have been no outcome studies with follow-up of longer than 2 years. Thirty-five patients with adolescent idiopathic scoliosis treated by the Wisconsin procedure between 1984 and 1987 were reviewed by radiographs, physical examination, and an outcome scale. Minimum length of follow-up was 5 years with an average of 6.3 years. Curves were corrected from a mean of 59 degrees preoperatively to 32 degrees postoperatively (46%), and 36 degrees at final follow-up (39%). Wisconsin segmental spinal instrumentation did not increase thoracic kyphosis. There was evidence of slight lumbar flattening in long fusions. According to the criteria described, 92% had a successful outcome. Complications of the procedure included two wound infections (one superficial, one deep), one rod displacement, and two wire breakages. No pseudarthroses or neurologic complications were identified in this series. Wisconsin segmental spinal instrumentation safely achieves the objectives of partial correction, arthrodesis, and early return to function. The technique may still have a role, particularly in the thoracic region, in selective thoracic fusion of King type II curves, rigid curves, and double thoracic curves.

Adolescent↗

Identification of a novel cyclin-like protein in human tumor cells.

Cyclins are key regulatory proteins that, in concert with cyclin-dependent protein kinase subunits (cdks), function to govern critical transitions and/or restriction points during the course of cell cycle progression. Recently, a number of putative mammalian G1 cyclins have been characterized at the molecular level; however, the specific activities of the cyclin/cdk complexes and the precise biochemical pathways regulated by the G1 cyclins remain to be elucidated. In the present study we identify a novel cyclin-like protein in pediatric bone and extremity tumors that appears to be related to, but is clearly distinct from, previously identified members of the cyclin D family, as determined by its profile of antibody cross-reactivity, apparent molecular size, chromatographic behavior, physicochemical properties, and pattern of peptide mapping. This 46-kDa cyclin-like protein, tentatively designated p46cyclin X, is first expressed in synchronized MG-63 osteosarcoma cells in mid-G1, well after the induction of p36cyclin D1, yet prior to the induction of cyclins E and A. Northern analysis, utilizing an oligonucleotide probe complementary to an epitope shared by cyclins D1, D2, and X, detected a novel mRNA species, the appearance of which correlates with p46cyclin X expression. The p46cyclin X protein in Ewing's sarcomas and Wilms' tumors is electrophoretically and chromatographically distinct from both p36cyclin D1 and p34cyclin D2. Moreover, the p46cyclin X protein is 1) precipitated by p9Ckshs1-agarose beads, 2) physically associated with p33cdk2, and 3) autophosphorylated in in vitro kinase reactions. Taken together with the biochemical data, the temporal expression of the p46cyclin X/p33cdk2 kinase system is suggestive of a potential role in regulating latter G1 events (i.e. START) in the commitment to S phase.

Amino Acid Sequence↗

Avoiding paraplegia during anterior spinal surgery. The role of somatosensory evoked potential monitoring with temporary occlusion of segmental spinal arteries.

Three patients paraplegic following anterior spinal fusion for congenital kyphoscoliosis were noted to have complete somatosensory evoked potential signal loss shortly after segmental arterial ligations at the apex of their respective kyphosis. This has prompted us to use temporary segmental arterial occlusion with somatosensory evoked potential monitoring prior to ligation during anterior spinal fusion. As a result, we have noted seven additional cases, out of a total of 44 cases monitored in this fashion, in which complete loss of somatosensory evoked potential signals, reversible by release of vascular clips, has occurred. For each of these additional cases the critical segmental arteries were identified and were not ligated, usually resulting in some modifications in the planned surgical procedure, and the patients remained neurologically intact. We recommend temporary segmental arterial occlusion with somatosensory evoked potential monitoring during thoracolumbar anterior spinal fusion to potentially avert ischemic neurologic injury. Based on published data and the experience described herein, this technique should be especially important in anterior spinal fusion for congenital kyphoscoliosis.

Adolescent↗

The incidence and natural history of scoliosis in Rett syndrome.

A survey on spinal deformity was conducted by means of a questionnaire mailed to the 350 American families who are members of the International Rett Syndrome Association. 258 questionnaires were completed and further information (medical records and radiographs) was received from treating physicians. Scoliosis was present in 119 patients, whose clinical details are discussed. Patients with Rett syndrome frequently develop progressive scoliotic deformities. The incidence increases with age, occurring most commonly during the second decade. Bracing to control curve progression has been largely unsuccessful for adolescent patients.

Adolescent↗