Mutations responsible for Larsen syndrome cluster in the FLNB protein.

BACKGROUND: A gene for Larsen syndrome was recently described, and mutations were reported in five cases. OBJECTIVE: To test whether mutations in this gene, FLNB, could explain the disease in our independent collection of sporadic and dominant Larsen syndrome cases; and to test whether mutations occurred in a non-random pattern. RESULTS: Missense mutations were found in each of five cases. Four of the five were new; one was reported in a sporadic case in the original Larsen syndrome study of five cases. All mutations from the two studies were compiled. Clustered mutations were observed within three filamin B protein domains: the calponin homology 2 domain, repeat 14, and repeat 15. This suggested that as few as five (of the total of 46) coding exons of FLNB could be screened to detect Larsen syndrome mutations. Four of these exons were screened in a sixth (sporadic) case and a previously reported G1691S substitution mutation detected. CONCLUSIONS: Mutations in FLNB may be responsible for all cases of Larsen syndrome. They appear to occur in specific functional domains of the filamin B protein. This should simplify diagnostic screening of the FLNB gene. Analyses in larger patient series are warranted to quantify this. The study confirmed the extreme variability in clinical presentation and the presence of unaffected carriers. A molecular screen would be valuable for diagnosis and genetic counselling.

Efficacy of perioperative halo-gravity traction in the treatment of severe scoliosis in children.

SUMMARY: Perioperative halo traction was used in the treatment of severe scoliosis in 19 children. Diagnoses included neuromuscular, idiopathic, and congenital scoliosis. Traction was transferable between the bed and a walker or wheelchair. Thirteen patients had prior spinal surgery, and most required osteotomy. Traction was used for 6 to 21 weeks. All patients underwent spinal fusion surgery after traction, with instrumentation used in 15 patients. Improvement was achieved in all patients. The Cobb angle improved 35% from an average 84 degrees before traction (range 63 degrees -100 degrees ) to 55 degrees preceding fusion. Trunk decompensation improved in all patients. Trunk height increased 5.3 cm in traction. Response to traction did not correlate with diagnosis, patient age, or prior surgery. There were no neurologic complications. Perioperative halo-gravity traction improves trunk balance and frontal and sagittal alignment in children with severe spinal deformity. Surgical fusion was enhanced by the improved alignment, and neurologic injury was avoided.

Mechanical testing of a single rod versus a double rod in a long-segment animal model.

This study involved the mechanical testing of single-rod segmental hook fixation and double-rod segmental hook fixation in a long-segment animal model. The goals were first to compare the flexibility of a single-rod scoliosis construct with that of a double-rod construct when tested in torsion, and second, to determine the effect of not using instrumentation with every vertebral segment for the single rod. Another study found that the single-rod construct was as stiff in torsion as the standard double-rod construct in a model of 10 vertebral segments. The amount of neutral zone (NZ) rotation was tested in five calf spines using an MTS (Material Testing System) machine. Five constructs were tested and included 1) a single rod with hooks at every level except the apex; 2) a single rod with two fewer hooks; 3) a single rod with four fewer hooks; 4) a double-rod construct; and 5) no instrumentation. The amount of NZ rotation between vertebral segments was measured over 12, 10, 8, 6, 4, and 2 vertebral segments. An analysis of variance with all constructs showed that the instrumented spines had significantly less movement than did the uninstrumented spine. Statistical comparison using analysis of variance of constructs (constructs 1 to 4) showed that over 12 vertebral segments (T4-L3), all single-rod constructs (constructs 1 to 3) allowed more NZ rotation than did the standard double-rod construct. This testing indicated that over 12 vertebral segments the single rod allowed more NZ rotation than a double-rod construct.

Localization of susceptibility to familial idiopathic scoliosis.

STUDY DESIGN: Genome-wide linkage surveys in large multiplex families with apparent inherited idiopathic scoliosis. OBJECTIVE: To identify chromosomal loci encoding genes involved in susceptibility to idiopathic scoliosis by positional cloning. SUMMARY OF BACKGROUND DATA: Although the inheritance of idiopathic scoliosis most often exhibits a complex pattern, autosomal dominant inheritance can be identified in some families. Families exhibiting such an inheritance pattern present an opportunity to identify the predisposing gene(s) by positional cloning. METHODS: Probands having clinically relevant idiopathic scoliosis (50 degrees Cobb angle) from large multiplex families were identified. A curve of 15 degrees, made from standing posteroanterior radiographs, was required for a positive diagnosis. A genome-wide search in one large family (seven affected members) was conducted with 385 polymorphic microsatellite markers spaced at an approximate 10-cM resolution. Hot spots identified in this family were subsequently tested in a second large kindred. RESULTS: Maximum evidence of allele-sharing in affected individuals from the first family was detected for three loci on chromosomes 6p, distal 10q, and 18q with nonparametric lod scores of 1.42 (P = 0.020), 1.60 (P = 0.019), and 8.26 (P = 0.002), respectively. Evidence of allele-sharing was also detected in the second family at distal chromosome 10q (nonparametric lod score = 2.02; P = 0.033). CONCLUSIONS: These data indicate a limited number of genetic loci predisposing to idiopathic scoliosis.

A comparison of single-rod instrumentation with double-rod instrumentation in adolescent idiopathic scoliosis.

STUDY DESIGN: A consecutive series of patients with idiopathic scoliosis treated with single-rod instrumentation was followed prospectively. Outcomes were compared with results obtained from a retrospective review of a consecutive series of patients treated with double-rod instrumentation. OBJECTIVE: To compare single-rod instrumentation with segmental fixation with double-rod instrumentation for the treatment of adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Mechanical testing of single-rod instrumentation with segmental fixation at every level showed it to be as resistant to torsion as a double-rod construct. A clinical trial was initiated to document the clinical outcome in single-rod patients. METHODS: A total of 43 of 51 consecutive patients underwent spinal fusion with a single rod. Outcome was evaluated at a minimum of 2 years after surgery. The control group comprised 103 patients who had standard double-rod instrumentation at the same institution. RESULTS: The single- and double-rod groups were similar with respect to age, sex, curve type, length of follow-up, curve magnitude, and best bend. For King III-V curves undergoing posterior spinal fusion, there was significantly less blood loss in the single-rod group (703 mL vs 1011 mL), less cell saver collection (189 mL vs 367 mL), and less operating time (220 minutes vs 260 minutes). Blood loss and operating time were not different for patients with King I and King II curves. There were eight patients (19%) requiring reoperation because of hardware-related problems in the single-rod group compared with four (4%) in the double-rod group. There were nine patients (21%) with broken rods in the single-rod group, six of whom were symptomatic and five of whom required reoperation. Two patients required multiple operations because of pseudarthrosis in the single-rod group. There were no broken rods in the double-rod group. The single-rod group had 2 early postoperative infections and no late infections compared with 10 late infections in the double-rod group. There was a statistically significant relationship between hardware problems and fusion below L1 in the single-rod group. CONCLUSION: Because of rod failure, single-rod instrumentation should be considered only in curves that can be instrumented to L1 and higher.

Relationship of peak height velocity to other maturity indicators in idiopathic scoliosis in girls.

BACKGROUND: Our aim was to compare height velocity data, obtained from clinical height measurements, for girls who had idiopathic scoliosis with the data for adolescents who did not have scoliosis. We also compared the growth data with chronological age, menarchal age, and Risser sign in terms of their accuracy in the prediction of growth and progression of the scoliosis. METHODS: One hundred and twenty of 371 patients in a database of girls managed with a brace for the treatment of idiopathic scoliosis had sufficient height data for us to quantify their growth peak. Height velocity data was generated from standing-height measurements obtained, in a scoliosis clinic, with a minimum six-month interval between measurements, and the timing of peak height velocity was calculated. The age at menarche was recorded from the patients' records. The Risser sign and Cobb angle were determined by a single observer. Progression of the scoliosis was defined as an increase in the Cobb angle of at least 10 degrees, compared with the curve magnitude at the time of the initial evaluation, after a minimum of six months. Progression to a magnitude requiring surgery was defined as progression of at least 10 degrees to a magnitude of 45 degrees or more. RESULTS: The height velocity plot grouped by peak height velocity showed a high peak and a sharp decline with values similar to those in normal populations. Extrapolating from percentile charts, 90 percent of our patients ceased growing by 3.6 years after peak height velocity. The growth peak was blunted (averaged over too long a period such that the data for the period of most rapid growth was averaged in with that for a period of slower growth) when chronological age, menarchal age, and Risser sign were used to predict growth; this indicated that these maturity scales grouped the patients poorly in terms of growth. The primary curve was progressive in eighty-eight of the 120 patients. Sixty of these patients had a curve of more than 30 degrees at peak height velocity, and in fifty (83 percent) of the sixty the curve progressed to 45 degrees or more. The remaining twenty-eight patients had a curve of 30 degrees or less at peak height velocity, with only one curve (4 percent) progressing to 45 degrees or more. Peak height velocity also grouped patients for maximal progression of the curve more accurately than did the other maturity scales, as most of the curves progressed maximally at peak height velocity. There was a wider spread of timing of maximal progression when chronological age, menarchal age, and Risser sign were used to predict progression. CONCLUSIONS: Height velocities generated from clinical height measurements for patients with idiopathic scoliosis document the growth peak and predict cessation of growth reliably. Knowing the timing of the growth peak provides valuable information on the likelihood of progression to a magnitude requiring spinal arthrodesis.

Developmental coxa vara associated with spondylometaphyseal dysplasia (DCV/SMD): "SMD-corner fracture type" (DCV/SMD-CF) demonstrated in most reported cases.

BACKGROUND: This paper reports three children with short stature: developmental coxa vara unilateral in the first case and bilateral in the other two; somewhat squared and "ovoid" vertebral bodies in the first patient, and normal to slightly tall vertebral bodies in the third; metaphyseal changes in some long tubular bones including bone fragments similar to the corner fractures seen in child abuse in all three patients. MATERIALS AND METHODS: The first and second patients were sisters; their mother, also quite short, had surgical procedures in early life for bilateral "coxa vara"; their brother, also of short stature, had bilateral coxa valga with otherwise normal femoral heads and necks, and mild metaphyseal changes associated with two minute "corner fractures" in the proximal metaphysis of the left tibia. RESULTS: A review of reported cases of developmental coxa vara associated with spondylometaphyseal dysplasia revealed that simulated corner fractures were present in most instances.

Outcome of ultrasonographic hip abnormalities in clinically stable hips.

A retrospective review was performed of 192 newborn hips in 112 patients referred for hip evaluation. The average age at presentation was 12.7 days, with average radiographic follow-up of 15.9 months. Inclusion criteria for our study were a normal physical examination of the hip without evidence of instability and an ultrasound examination that was considered abnormal. Pavlik harness treatment was chosen at the discretion of the treating physician. At final follow-up, dysplasia was defined as greater than two standard deviations above the mean acetabular index (AI) for age. Group I consisted of 43 hips that had Pavlik treatment, and group II consisted of 149 hips that did not receive treatment. There was no difference in these two groups with respect to risk factors for dysplasia or the initial abnormalities seen on ultrasound evaluation, although patients in group I had less coverage of the femoral head during stress maneuvers. No hip in group I and two (1.3%) hips in group II were considered dysplastic (AI > 2 SD) at final radiographic follow-up (p > 0.10). There was no correlation between the severity of the ultrasound abnormality at birth and the subsequent presence of dysplasia (p > 0.10). The two hips considered dysplastic on radiograph were not being actively treated. When the hip examination of a newborn hip younger than 1 month is normal, a screening ultrasound does not appear to predict accurately subsequent hip dysplasia. In this specific setting, an initial screening ultrasound may be too sensitive and does not appear warranted.

The control of bovine virus diarrhoea virus in Shetland.

A scheme to control and eradicate bovine virus diarrhoea (BVD) was initiated in 1994 in the Shetland Islands by local veterinary surgeons and funded by the Shetland Islands Council and Shetland Enterprise Company. Over a 3-year period every bovine animal on the islands was blood-sampled (heparinised) and laboratory tested using MAb-based ELISAs for BVD virus antibody and antigen detection for evidence of disease. A number of BVD virus positive animals (40) were found and culled. A total of 6150 animals were tested from 213 herds and 43% herds were found to be BVD naive. The remaining herds had experienced infection and contained many BVD antibody positive animals. Some repeat sampling of stock in infected herds determined further virus positive animals which were slaughtered and in 1997 the scheme ceased since it appeared that there were no persistent excretors present. The major risk to the Shetland Islands is from bought-in stock, especially animals which are imported in calf. It is vital that all bought-in animals are tested and proven to be free of BVD virus if these animals are in calf, the calves must be tested a birth to determine status. It is strongly advised that only bulls and bulling heifers or cows are bought into Shetland in future, thus, protecting the present stock. Continued surveillance will be required to claim eradication of BVD from Shetland.

Chronic musculoskeletal pain in childhood.

We studied 73 children with chronic or recurrent musculoskeletal pain of > or = 6 weeks' duration. Thirty-six children had no identifiable organic etiology for their pain, with a minimum follow-up of 2 years for ongoing symptoms. Thirty-seven children had an organic etiology for their pain. Use of an Inappropriate Symptom Checklist was helpful in distinguishing between children with chronic pain who were found to have an organic disease and those without an identifiable organic disease. Seventy-seven percent of children with no inappropriate symptoms had an organic diagnosis ultimately made. Conversely, 79% of children with two or more inappropriate symptoms ultimately had no organic diagnosis to explain their pain. Behavioral self-report measures testing could not differentiate between children with chronic pain with or without organic disease. Intervention by a psychologist skilled in pain management was helpful.

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 degrees to 45 degrees, 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 degrees-45 degrees, in whom 83% of the those treated with a Charleston brace had curve progression of more than 5 degrees, 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.

Multiple synchronous primaries of the gastrointestinal tract: a molecular case report.

Six synchronous gastrointestinal primaries were identified in a 70 year old male with no known cancer predisposition syndrome or recognized risk factors except alcohol abuse. These specimens appeared to be independent and unrelated by gross and histopathological examination. In order to further evaluate the six tumors, we analyzed selected DNA sequences for alterations in the K-ras oncogene and p53 tumor suppressor gene. In addition, three loci were analyzed to determine microsatellite instability. Using the polymerase chain reaction, single stranded conformational polymorphism, and DNA sequencing, we demonstrated that each primary manifests genetic characteristics typical of the tissue of origin. In addition, one primary, a moderately differentiated colon adenocarcinoma, exhibited mutations not detected in the other specimens. This study suggests that these synchronous primaries arose independently and progressed along different carcinogenic pathways.

Severe lumbar lordosis after dorsal rhizotomy.

Two children with spastic quadriplegia who developed excessive lumbar lordosis after selective dorsal rhizotomy are described. The rhizotomy did not change the ambulatory status of either child (one nonambulator, one household ambulator). Preservation of unopposed hip flexion in the presence of multiple laminectomies may lead to the development of a lordotic deformity in children who sit most of the time. Excessive lumbar lordosis may cause pain and difficulty in sitting. Surgical correction of this deformity is complex because of the removal of posterior elements during the rhizotomy.

K-ras mutation in a tubular adenoma originating at an ileostomy in a familial adenomatous polyposis patient.

Genetic alterations in a tubular adenoma with severe dysplasia arising in a Brooke ileostomy of a familial adenomatous polyposis patient were analyzed. Clinical and morphological characteristics suggest that ileal mucosa progressed to colonic metaplasia and then to dysplastic adenoma. Such changes at ileostomy sites are rare, and little is known about the associated genetic alterations. To determine whether metaplastic epithelium progression to adenoma in the ileum is subject to the same mutations identified in colon carcinogenesis, we evaluated somatic genetic alterations associated with sporadic colorectal cancer development. Sequences examined included mutation cluster regions of the p53 tumor suppressor gene and the k-ras oncogene. Using polymerase chain reaction and DNA sequencing, we identified a point mutation at codon 12 of the K-ras oncogene. To our knowledge, this is the first report of a ras mutation occurring in a tumor originating from ileal mucosa.

Molecular oncology and the surgeon.

The last 20 years have witnessed a flood of new developments and discoveries in the fields of molecular biology and oncology. Dozens of human genes associated with cancer predisposition syndromes and the malignant and metastatic process have been identified and characterized. These findings have led to a greater understanding of this complex disease and inaugurated a new era of investigations seeking more effective diagnostic protocols and therapies. This review summarizes a few of the many salient discoveries and discusses the clinical implications for the surgeon.

Posterior arthrodesis and instrumentation in the immature (Risser-grade-0) spine in idiopathic scoliosis.

We performed a retrospective study of the long-term results of posterior instrumentation and arthrodesis of the spine in forty-three patients who had idiopathic scoliosis and a Risser grade of 0 at the time of the operation. The average age of the patients was 12.4 years (range, 6.7 to 15.5 years) at the time of the operation. The triradiate cartilages were open in twenty-three patients and closed in twenty. At the time of the latest follow-up evaluation (average duration of follow-up, four years; range, two to eleven years), seventeen patients had a Risser grade of 5; twenty-two, 4; two, 3; one, 2; and one, 0. The crankshaft phenomenon, a progressive deformity resulting from continued growth of the anterior aspect of the spine after posterior arthrodesis, was seen in only one patient who had closed triradiate cartilages and in ten patients who had open triradiate cartilages (p = 0.004). The most common radiographic finding was a progressive rib-vertebra angle difference, which increased more than 10 degrees in seven of the eleven patients who had the crankshaft phenomenon. The mean increase in these eleven patients was 22 degrees, compared with no increase in the thirty-two other patients (p < 0.0001). Open triradiate cartilages (r = 0.58, p = 0.0001) and a younger age at the time of the operation (p < 0.0001) were predictive of the amount of progression as a result of the crankshaft phenomenon. In patients who had open triradiate cartilages, less skeletal maturity was also predictive of progression as a result of the crankshaft phenomenon (r = -0.72, p = 0.0002).

Bone age determination in children with Legg-Calvé-Perthes disease: a comparison of two methods.

In 100 children (17 girls, 83 boys) with Legg-Calvé-Perthes disease, the average chronological age, pelvis bone age, and hand-wrist bone age were significantly different for the girls (8.2, 6.9, and 7.0 years, respectively; p < 0.05) and the boys (8.2, 7.4, and 5.9 years, respectively; p < 0.05). For the girls, the chronological age was greater than the pelvis bone age and the hand-wrist bone age (p < 0.05); there was no difference between the pelvis and hand-wrist bone age. For the boys, the chronological age was greater than the pelvis bone age and the hand-wrist bone age (p < 0.05); the pelvis bone age was greater than the hand-wrist bone age and less than the chronological age (p < 0.05). The acromelic growth in Legg-Calvé-Perthes disease may explain why the more proximal pelvis bone age in boys was less delayed than that of the more distal hand-wrist.