Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism.

PURPOSE: To identify the gene causing tarsal/carpal coalition syndrome (TCC). METHODS: Individuals from three kindreds with TCC and normal hearing were used to map TCC and screen for mutations in Noggin (NOG). RESULTS: Three different missense mutations in NOG were found. Two of these mutations are identical to mutations previously reported to cause proximal symphalangism (SYM1). CONCLUSIONS: TCC is allelic to SYM1, and at least two different mutations in NOG can result in either TCC or SYM1 in different families. This finding suggests that phenotypic differences between these conditions are caused by epistatic modifiers of NOG.

Recurrent Legg-Calvé-Perthes disease: case report and long-term followup.

This is the seventh reported case of recurrent Legg-Calvé-Perthes disease. The report documents the initial onset in a boy 4 years of age with healing clinically and radiographically. The boy experienced recurrence of disease at 8 years of age with last followup at 20 years of age. Tests related to blood hypercoagulability and hypofibrinolysis and certain genetic factors relevant to osteonecrosis of the bone are reported.

Poland's syndrome in one identical twin.

Female twins were evaluated at the Shriners Hospital in Lexington, Kentucky. One twin was normal, and the other twin had the classic findings of Poland's syndrome, manifested by absence of the pectoralis major and symbrachydactyly of the right upper extremity. Buccal smears from each child were submitted for DNA testing. The test confirmed monozygosity with 99.9% probability. Some previous reports have stated that Poland's syndrome is an autosomal dominant, genetically determined trait, whereas others have maintained that there is no genetic association. The original case described by Poland in 1841 was his cadaver, and no family history was reported. This twin study provides strong evidence that the condition is not determined by gene transmission.

Involvement of OSP/claudin-11 in oligodendrocyte membrane interactions: role in biology and disease.

Oligodendrocyte-specific protein (OSP/claudin-11) is a four transmembrane protein concentrated in central nervous system myelin. Recent evidence has emerged suggesting that OSP/claudin-11 is involved in membrane interactions at tight junctions and with the extracellular matrix. OSP/claudin-11 seems to modulate proliferation and migration of oligodendrocytes presumably through these interactions. Furthermore, evidence is presented implicating OSP/claudin-11 as an autoantigen in the development of autoimmune demyelinating disease.

Oligodendrocyte-specific protein peptides induce experimental autoimmune encephalomyelitis in SJL/J mice.

Oligodendrocyte-specific protein (OSP) is a recently isolated and cloned, 207-aa, hydrophobic, four-transmembrane protein found in CNS myelin. It represents approximately 7% of total myelin protein. The OSP cDNA sequence has no significant homology with previously reported genes, but the predicted protein structure suggests that OSP is a CNS homologue of peripheral myelin protein-22. We previously reported the presence of anti-OSP Abs in the cerebrospinal fluid of relapsing-remitting multiple sclerosis (MS) patients, but not control patient groups. In this study, we tested the ability of a panel of 20-mer peptides with 10-aa overlaps, representing the sequence of murine OSP, to induce experimental autoimmune encephalomyelitis (EAE), an animal model for MS. SJL mice challenged with murine OSP peptides 52-71, 82-101, 102-121, 142-161, 182-201, and 192-207 exhibited clinical EAE. OSP:52-71 elicited severe relapsing-remitting EAE in some individuals. All other encephalitogenic peptides elicited, at most, a loss of tail tonicity from which the mice most often completely recovered. Mononuclear cell infiltrates and focal demyelination characteristic of EAE were evident. T cell proliferative responses were seen with all encephalitogenic peptides except 142-161 and 182-201. OSP peptides 72-91 and 132-151 did not cause clinical EAE, but did elicit robust proliferative responses. B10.PL and PL/J mice challenged with the same OSP peptide doses as SJL mice did not exhibit clinical EAE. These results in the SJL EAE model, together with the results from MS patient clinical samples, make OSP a promising candidate for autoantigenic involvement in MS.

Increased neurologic complications associated with postoperative epidural analgesia after tibial fracture fixation.

A retrospective study of 63 patients with surgically treated tibial fractures was performed. The type of postoperative analgesia was compared against the type of fracture, mechanism of injury, type of fixation, adequacy of pain control, and incidence of neurologic complications. The only difference observed among all of these comparisons was that patients given postoperative epidural analgesia with local anesthetics were 4.1 times more likely to have a neurologic complication than those receiving systemic narcotics (P = 0.0496). We conclude that patients who have undergone surgical treatment of tibial plateau or shaft fractures have a significantly higher risk of developing neurologic complications when post-operative epidural analgesia is used.

The progression of untreated lumbar kyphosis and the compensatory thoracic lordosis in myelomeningocele.

Radiographs of 37 patients with untreated lumbar kyphosis without congenital vertebral anomalies associated with myelomeningocele were analyzed. With an average interval between radiographs of 6.2 years, the kyphosis was noted to increase at a mean rate of 4.3 degrees per year without correlation to its initial magnitude. The compensatory lordosis was more variable and progressed at a mean of 2.5 degrees per year. Children under the age of 2 years were more likely to increase the Cobb angle and the height of their kyphosis. There was an inverse relationship between the height of the kyphus and the lumbar spine height and the resultant growth of each. A modified kyphotic index less than 4 correlated with an increase in the curve and height of the kyphosis and the subsequent desire for surgery. Wide variability in radiographic parameters make predictions for an individual patient difficult.

Modified Mitchell bunionectomy for management of adolescent hallux valgus.

This retrospective review was performed to determine results and to present a new operative method, a modified Mitchell procedure, used to treat 13 adolescents with a total of 21 bunions. The average age of the patients was 14 years, 6 months. The average clinical followup period was 31 months. The average preoperative valgus angle was 35 degrees (range, 21 degrees-65 degrees); the average preoperative intermetatarsal angle was 14 degrees (range, 7 degrees-22 degrees). The early operative result for 17 feet (81%) was satisfactory; deformity, pain, or stiffness recurred in 4 feet (19%). At the time of the last clinic visit, the average hallux valgus angle was 15 degrees (range, 3 degrees-43 degrees); the average intermetatarsal angle was 7 degrees (range, 2 degrees-18 degrees). No instances of malunion, nonunion, infection, avascular necrosis, or transfer metatarsalgia occurred. This modification of the Mitchell procedure is an effective management option for mild to moderate adolescent hallux valgus.

Use of Ilizarov external fixator to treat joint pterygia.

Joint pterygia are rare conditions characterized by joint-flexion contractures and webbing of the overlying skin and subcutaneous structures. Treatment is difficult because the neurovascular bundle is often displaced into the web, and only moderate success has been reported with past treatment options. A retrospective review was performed on five patients with six involved joints: two antecubital pterygia and four popliteal pterygia. The Ilizarov technique was used for gradual correction of pterygia through the joint (arthrodiastasis). Primary treatment goals included improvement in functional extension, hygiene independence, and cosmesis. Ambulation was also an objective in the patients with popliteal pterygia. For inclusion in this study, a minimum of 2 years' follow-up was required after the device was removed. Preoperative goals were met in four of the six joints. Initial improvement in total arc of motion was noted; however, some regression was common. Complications were frequent, and there was a learning curve for proficiency with the Ilizarov technique. We believe that the Ilizarov technique provides a treatment option for antecubital and popliteal pterygia.

In situ fixation of the slipped capital femoral epiphysis with a single screw.

We made a retrospective analysis of a consecutive series of patients with slipped capital femoral epiphyses (SCFE) surgically treated at the Shriners Hospitals for Crippled Children at Lexington, Kentucky. The clinical outcome was correlated to the number of pins and the incidence of chondrolysis, ischemic necrosis, and progressive slipping after the initial fixation. An evaluation made of the Walters-Simon theoretic pin penetration formula was of no value in this series. We compiled results in the medical literature and compared them with ours; all information indicated that a single pin through an anterior portal significantly reduces complications and provides reliable fixation. However, ischemic necrosis still occurs in the unstable slip, although at a lesser rate than in cases treated with multiple pin fixation.

Heel cord advancement in children with spastic equinus deformity.

Heel cord advancement has been advocated for treatment of spastic equinus deformity. Transferring the gastrosoleus anteriorly weakens it by changing the lever arm rather than the resting length. A retrospective review of 90 children with 122 limbs undergoing heel cord advancement revealed 11% excellent, 53% good, and 35% poor results (average follow-up 9.7 years). The results were statistically better in diplegics and community walkers. The better results in previous studies may be due to procedure modifications and shorter follow-up. Since we obtain comparable results with simpler heel cord lengthenings, we no longer do heel cord advancement.

Spinal deformity in Charcot-Marie-Tooth disease.

STUDY DESIGN: This retrospective study reviewed 100 children with clinically and electrodiagnostically proven Charcot-Marie-Tooth disease (CMTD). OBJECTIVE: To determine the incidence of spinal deformity in children with CMTD. SUMMARY OF BACKGROUND DATA: A 10% incidence of kyphoscoliosis has been reported. METHODS: All charts and electrodiagnostic studies were reviewed to confirm that CMTD diagnostic criteria were met. Existing radiographs on 89 children were available. Cobb angles were measured and deformity was defined as scoliosis > or = 10 degrees and kyphosis > 40 degrees. RESULTS: Thirty-seven of 89 CMTD children had spinal deformity. There was scoliosis in 20, kyphoscoliosis in 14, and kyphosis in 3. In children with radiographs taken at maturity, 50% had deformity. The most common scoliotic pattern was a thoracic curve with convexity in either direction. Spinal deformity is more likely in female and Type I patients. CONCLUSIONS: This study found an incidence of 37%-50% spinal deformity in children with CMTD, with female and Type I patients at greatest risk. However, the deformity rarely required treatment.

Transforming growth factor-beta 1 inhibits tumor necrosis factor-alpha/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis.

We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce transforming growth factor-beta (TGF-beta). We also reported that TGF-beta downregulates interferon-gamma (IFN-gamma), but not interleukin-2 (IL-2) production, by the CD4+ effector T cells (Te) that mediate EAE. We now report that TGF-beta also inhibits the production of tumor necrosis factor/lymphotoxin (TNF/LT) by EAE effector cells. When activated in vitro with myelin basic protein (MBP), Te produced TNF/LT, as measured using a WEHI 164 cytotoxicity assay. The specificity of cytokine action was demonstrated using neutralizing antibodies to TNF/LT. When added to the Te+MBP cultures, TGF-beta inhibited TNF/LT production in a dose-dependent fashion. Moreover, neutralizing anti-TGF-beta antibodies augmented TNF/LT production in the Te+MBP cultures. We also confirm that TGF-beta inhibits adoptive transfer of EAE. In contrast, murine IL-10 only partially inhibited TNF/LT and IFN-gamma production by Te. We conclude that TGF-beta production by Ts plays a major role in recovery from EAE in the Lewis rat by inhibiting TNF/LT and IFN-gamma production by the effector cells that mediate EAE.

Hip abnormalities in children with Charcot-Marie-Tooth disease.

Hip dysplasia was recently observed in association with Charcot-Marie-Tooth disease (CMT). We retrospectively reviewed available radiographs of 74 of 100 children with clinically and electrodiagnostically proven CMT and noted six cases of hip dysplasia. Minor hip abnormalities, most commonly increased neck shaft angles, were noted in 21 other patients. Type I usually causes more weakness and had more hip dysplasia than type II. A female predominance was noted but may have resulted from sampling of more immature radiographs in males. Most dysplasia was asymptomatic and was detected only on screening radiographs.

Injury patterns in motorcycle road racers: experience on the Isle of Man 1989-1991.

We report the first prospective study on the incidence of motorcycle accidents of the world's foremost motorcycle road-racing venue, the Isle of Man. Between 1989 and 1991 there were six meetings during which over 2500 riders took part. Racing on essentially normal country and town roads, the motorcycles can reach speeds in excess of 306 km/h and the average lap record is now 198 km/h. During the study, 175 motorcyclists were injured and 16 were killed (9.1 per cent). The most common injury patterns were soft tissue injury (114 riders), head injury (52) and fractures/dislocations (188), of which one-third were open. The injuries sustained were more frequent and of a greater severity than recreational motorcycling. The casualty rate was 15 times, and the fatality rate 87 times the national figures. Of the 16 fatalities only seven reached hospital alive, despite the use of helicopter air ambulance, and 14 had serious head injuries. No fatality was thought to have been avoidable on review. There were no cervical spine injuries and only two major abdominal injuries. Of the injured riders, 93 (56 per cent) were admitted and there were 170 surgical procedures undertaken on 54 riders.

Helicopter transfer of trauma patients: the Isle of Man experience.

A 10-year study of the helicopter transfer of motorcyclists injured during the International Motorcycle Tourist Trophy races (TT) and the amateur Manx Grand Prix (MGP) is reported. A total of 266 riders was transferred from the scene of the accident to hospital by air. The overall mortality rate for those riders airlifted was 3.38 per cent. The figures are compared with similar emergency helicopter services.

Bromodeoxyuridine and light treatment deletes effector but not suppressor cells of autoimmune encephalomyelitis.

Spleen cells (SpC) from Lewis rats that have recovered from experimental autoimmune encephalomyelitis (EAE) confer protection against EAE to naive syngeneic recipients if transferred directly (without culture), but transfer EAE if first activated in culture in the presence of myelin basic protein (MBP) antigen. In order to test the hypothesis that both effector (Te) and suppressor (Ts) cells of EAE coexist in recovered rats, but only the Te proliferate in culture in response to MBP, bromodeoxyuridine (BUdR) was added to the culture and dividing cells were killed by exposure to light prior to adoptive transfer. Recipients of BUdR+light-treated cells did not develop EAE, showing that Te were deleted by the treatment. In contrast, Ts activity persisted because these recipients were protected against EAE when challenged with an encephalitogenic dose of MBP.

Studies of V beta 8 T cell receptor peptide treatment in experimental autoimmune encephalomyelitis.

Lewis rats immunized with T cell receptor (TCR) variable region peptide V beta 8 in complete Freund's adjuvant (CFA) were protected against experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein in CFA, although variable protection was also observed in rats injected with control peptide in CFA, or CFA alone. However, this adjuvant-mediated protection could be avoided by immunizing with TCR peptide in incomplete adjuvant (IFA). Clinical, but not histologic EAE was suppressed in rats given V beta 8 peptide in IFA, whereas control animals injected with V beta 14 peptide in IFA, or IFA alone developed severe clinical EAE. Anti-V beta 8 antibodies were present in the sera of all V beta 8-treated rats. These findings lend support to the hypothesis that autoimmune disease can be suppressed by inducing an immune response against the TCR-idiotope of autoreactive T cells.

Segmental spinal instrumentation for neuromuscular spinal deformity.

Seventy-six consecutive surgical cases of paralytic neuromuscular spinal deformity were retrospectively analyzed. Posterior arthrodesis with segmental spinal stabilization with Luque L-rods, sometimes preceded by anterior release, was done in all cases. The infection rate of 14.5% was observed to be markedly higher in patients with myelodysplasia. Deep placement of the rods lateral to the spine and well beneath full-thickness skin is recommended to reduce the incidence of this complication.

Slipped capital femoral epiphysis. Treatment by pinning in situ.

This paper retrospectively reviews 46 hips in 33 patients treated for slipped capital femoral epiphyses (SCFE) between December 1964 and January 1983. The average clinical and roentgenogram follow-up evaluation was seven years. Twenty-nine patients had in-situ pinning and four had primary Southwick osteotomies. Eighty-nine percent of the patients treated had acceptable results. Unacceptable results were directly related to preoperative manipulation and/or pin penetration on x-ray. These results were not dependent on the degree of the slip, which ranged from 7 degrees-94 degrees.