Mesenchymal stromal cell injection promotes vocal fold scar repair without long-term engraftment.

BACKGROUND: Regenerative medicine holds promise for restoring voice in patients with vocal fold scarring. As experimental treatments approach clinical translation, several considerations remain. Our objective was to evaluate efficacy and biocompatibility of four bone marrow mesenchymal stromal cell (BM-MSC) and tunable hyaluronic acid based hydrogel (HyStem-VF) treatments for vocal fold scar using clinically acceptable materials, a preclinical sample size and a dosing comparison. METHODS: Vocal folds of 84 rabbits were injured and injected with four treatment variations (BM-MSC, HyStem-VF, and BM-MSC in HyStem-VF at two concentrations) 6 weeks later. Efficacy was assessed with rheometry, real-time polymerase chain reaction (RT-PCR) and histology at 2, 4 and 10 weeks following treatment. Lung, liver, kidney, spleen and vocal folds were screened for biocompatibility by a pathologist. RESULTS AND DISCUSSION: Persistent inflammation was identified in all hydrogel-injected groups. The BM-MSC alone treatment appeared to be the most efficacious and safe, providing an early resolution of viscoelasticity, gene expression consistent with desirable extracellular matrix remodeling (less fibronectin, collagen 1α2, collagen 3, procollagen, transforming growth factor [TGF]ß1, alpha smooth muscle actin, interleukin-1ß, interleukin-17ß and tumor necrosis factor [TNF] than injured controls) and minimal inflammation. Human beta actin expression in BM-MSC-treated vocal folds was minimal after 2 weeks, suggesting that paracrine signaling from the BM-MSCs may have facilitated tissue repair.

[Chondrocalcinosis of the temporomandibular joint revealed by a hearing loss: a case report]. / Une chondrocalcinose de l'articulation temporo-mandibulaire révélée par une hypoacousie: à propos d'un cas.

INTRODUCTION: Chondrocalcinosis is a microcrystalline arthropathy that principally affects the knee. It is a rare disorder, usually asymptomatic, that occurs mainly in the elderly people. PURPOSE: To report a case of a temporomandibular joint chondrocalcinosis with ossicular contact revealed by a conductive hearing loss. CASE REPORT: We describe the case of a 57-year-old man with a right conductive sudden hearing loss of 15 dB. The CT scan revealed a lytic lesion in the right attic extended to the middle cerebral fossa in contact with the ossicles with a suspicion of lysis of the head of the malleus. MRI showed a lesion enhancing after gadolinium injection on T1 weighted images. A biopsy revealed a chondrocalcinosis of the temporomandibular joint. Due to the complexity of surgical excision and the benin character of the lesion, a medical treatment and a radiologic follow-up every six months were proposed. CONCLUSION: Chondrocalcinosis of the temporo-mandibular joint is rare especially when it is revealed by a hearing loss. We present here a review of the literature.

Radiation-induced lipid peroxidation and the fluidity of erythrocyte membrane lipids.

The effect of radiation-induced peroxidation on the fluidity of the phospholipids of the erythrocyte membrane was studied using both erythrocyte ghosts and liposomes formed from the polar lipids of erythrocytes. In liposomes, the oxidation of the phospholipids increased with radiation dose, but there was no change in the fluidity of the lipids as measured by spin-label motion. Under the same conditions of irradiation, no oxidation of phospholipid was detected in erythrocyte ghosts, although changes occurred in the motion of spin labels intercalated with the membrane. These changes were attributed to radiation-induced alterations in the membrane proteins. It is concluded that alterations in motion of spin labels, observed with intact membranes after irradiation, are most likely the result of changes in the structure of membrane proteins rather than the lipids.

Measurement of splenic function with heat-damaged RBCs: effect of heating conditions: concise communication.

RBCs labeled with Cr-51 were heated in saline, and RBCs labeled with Tc-99m were heated in plasma or as packed cells. Blood clearances were then compared. Clearance for saline-heated cells was faster than for heated, packed cells, and much faster than for plasma-heated cells. RBCs heated in plasma for 20 min at 49.5 degrees C were insufficiently damaged for measurement of spleen function, but adequate spleen images were obtained in all patients, despite half-clearance times that varied from 14 min to over 90 min.

Hydrogen peroxide modulation of the respiratory burst of human neutrophils.

Addition of micromolar concentrations of hydrogen peroxide (H2O2) to human neutrophils resulted in a dose-dependent luminol-enhanced chemiluminescent response. Pretreatment of neutrophils with micromolar concentrations of H2O2 altered their response to the surface acting stimulants serum-treated zymosan (STZ) and formyl-methionyl-leucyl-phenylalanine (fMLP), but not to the intracellular stimulant phorbol myristate acetate (PMA). The alterations were partially reversible by catalase, but exacerbated by superoxide dismutase. These results suggest a modulatory role for H2O2 in the respiratory burst of neutrophils.

Evaluation and treatment of diastematomyelia.

We reviewed the results for forty-three patients who had a diastematomyelia. All of the patients had been skeletally immature when the diagnosis was made, the mean age being six years (range, birth to thirteen years), and were skeletally mature by the time that they were evaluated by us. When they were first seen at our institution, twenty-four patients (56 per cent) had a cutaneous lesion, such as hairy patch, dimple, hemangioma, subcutaneous mass, or teratoma at or near the level of the diastematomyelia; thirty-four patients (79 per cent) had congenital scoliosis; and forty-two patients (98 per cent) had at least one associated musculoskeletal anomaly, such as spinal dysraphism, asymmetry of the lower extremities, club foot, or a cavus foot. In twenty-seven patients (63 per cent), the diastematomyelia was located in the lumbar spine. Thirty-six patients had eighty-four neurological manifestations. Resection of the spur was performed in thirty-three patients at a mean age of seven years (range, three months to seventeen years). Twenty-two patients who had a resection had no change in neurological condition, nine patients had improvement, and one patient had one symptom improve and another symptom worsen after the operation. We believe that resection of the spur should be performed in patients who have progressive neurological manifestations. Patients who do not have progressive neurological manifestations should be observed; if progression is noted, a resection should then be performed.

Shelf arthroplasty in patients who have Legg-Calvé-Perthes disease. A study of long-term results.

We reviewed the long-term functional and roentgenographic outcomes of severe Legg-Calvé-Perthes disease in two similar groups of patients, one of which was managed with a shelf arthroplasty and the other, by a variety of non-operative means. Twenty hips in nineteen patients were treated with traction and, when necessary, adductor tenotomy to attempt reduction of the subluxation; this was followed by a shelf arthroplasty to increase the arc of the acetabulum and result in coverage of the femoral head. The average duration of follow-up was nineteen years (range, two to forty-seven years). The initial center-edge angle and the anteroposterior Mose sphericity measurement were significantly improved at the most recent follow-up (p greater than or equal to 0.05), and the average Iowa hip score was 91 points. Hinge abduction, which was producing incongruity, was eliminated in eleven of fourteen hips after the operation. The outcomes for the second group, consisting of eighteen hips in seventeen patients who were managed non-operatively, were also reviewed, at an average duration of follow-up of twenty-eight years (range, seven to forty-five years). No significant improvement in the center-edge angle or the anteroposterior Mose sphericity measurement was observed at the most recent follow-up, and the average Iowa hip score was 81 points. There was no significant difference in the range of motion of the hip between the groups. We believe that shelf arthroplasty is a favorable option in the treatment of Legg-Calvé-Perthes disease when additional bone is needed at the lateral aspect of the acetabulum to cover the extruded portion of the femoral head, to prevent additional incongruity and thereby delay the early onset of degenerative changes.

Congenital dislocation of the hip in boys.

Fifty-five boys with seventy-eight congenitally dislocated hips were treated between 1965 and 1990. The patients were divided into three groups according to the initial treatment. Group I included thirty hips (twenty-two boys) that had been treated initially with a Pavlik harness. Two hips (7 per cent) had a successful outcome, and twenty-eight (93 per cent) needed additional methods of treatment. Group II included forty-two hips (twenty-nine boys) that had been treated initially with closed reduction and immobilization in a hip-spica cast. After the closed reduction, twenty-nine hips (69 per cent) were considered stable, although fifteen (52 per cent) of them needed a secondary procedure because of residual subluxation or persistent acetabular dysplasia. Thirteen hips (31 per cent) were considered unstable after the closed reduction and subsequently had an open reduction. Group III included six hips (four boys) that had been treated initially with open reduction. Two of these hips redislocated after the open reduction, and they were reduced with an additional open reduction. A pelvic osteotomy was later performed to treat persistent acetabular dysplasia in these two hips. Two hips that had been treated with an open reduction and concomitant pelvic and femoral procedures did not need additional treatment. This study demonstrates that boys who have congenital dislocation of the hip do not always respond well to treatment and constitute a high-risk group.

Fibrous dysplasia of the proximal part of the femur. Long-term results of curettage and bone-grafting and mechanical realignment.

We reviewed the long-term outcomes of treatment of fibrous dysplasia of the proximal part of the femur in twenty-two patients (twenty-seven femora). There were fifteen male patients and seven female patients. Patients who had monostotic disease had no involvement of the calcar femorale, fewer microfractures, less deformity, and stronger bone that could support internal fixation. Patients who had polyostotic disease had frequent involvement of the calcar femorale; more microfractures; severe deformity, including shepherd's crook deformity; and, in many instances, bone that could not support internal fixation. Twenty-two of the twenty-seven femora had a microfracture at the time of the initial presentation. At least one osteotomy was performed in four femora that had monostotic disease and in nine femora that had polyostotic disease. Curettage and cancellous or cortical bone-grafting did not appear to have any advantage compared with osteotomy alone in the treatment of symptomatic lesions, as all grafts resorbed with persistence of the lesion. At the time of the latest follow-up evaluation, no lesion had been eradicated or had decreased in size. A satisfactory clinical result was achieved in twenty patients (twenty-four femora): nine who had monostotic disease and eleven who had polyostotic disease. Two patients who had polyostotic disease and an endocrinopathy (one of whom had bilateral involvement) had an unsatisfactory result. All three femora in these two patients had a neck-shaft angle of less than 90 degrees at the time of the most recent follow-up evaluation. Varus deformity of the proximal part of the femur is best treated with valgus osteotomy and internal fixation early in the course of the disease. If the calcar of the femoral neck is involved or if the quality of the bone is such that internal fixation is not possible, a medial displacement valgus osteotomy can provide a more mechanically favorable position for healing of the microfracture.

Osseous and non-osseous coalition of the middle facet of the talocalcaneal joint.

Sixteen patients (eighteen feet) who had a coalition of the middle facet of the talocalcaneal joint had operative resection of the coalition because nonoperative treatment, such as casts, failed to relieve the symptoms. The patients were symptomatic for an average of one and a half years (range, four months to two years) before they were seen by us. The average age at the time of the operation was fourteen years (range, seven to nineteen years). Three feet had resection with no material interposed, six had resection with interposition of fat, and nine had resection with interposition of half of the tendon of the flexor hallucis longus muscle. The average length of follow-up was four years (range, two to eight years). The result was excellent for eight feet, good for eight feet, and fair for one foot; for one foot, the result was poor because the coalition recurred. Three types of coalition were identified on preoperative computed-tomography scans that correlated with the operative findings. Type I was an osseous bridging of the middle facet joint (five feet). Type II (cartilaginous coalition) was marked narrowing of the middle facet joint with cortical irregularity (three feet). In Type III (fibrous coalition), there was only slight narrowing of the middle facet joint (ten feet). The type of coalition did not influence the result. Fibrous coalitions were the most difficult to detect; bone scintigraphy was used to confirm the diagnosis when other tests were equivocal. We believe that symptomatic coalition of the middle facet of the talocalcaneal joint should be treated with resection when non-operative methods fail to relieve symptoms.

Prognostic factors in congenital dislocation of the hip treated with closed reduction. The importance of arthrographic evaluation.

We reviewed the clinical records, arthrograms, and roentgenograms of sixty-one children who had seventy-two congenitally dislocated hips in an effort to identify factors that can be used to predict the outcome of treatment. Only patients who had been followed clinically and roentgenographically for a minimum of two years after the initial closed reduction were included in the study. The mean age at the time of closed reduction was thirteen months (range, three to forty-one months). The mean age at the time of the most recent follow-up was six years (range, two to fifteen years). The mean duration of follow-up after the initial closed reduction was five years (range, two to thirteen years). There was no statistical difference between the good, fair, and poor-result groups with regard to sex, the age at the initial reduction, the traction station, the side of involvement, the initial acetabular index, the initial grade of displacement, the effect of adductor tenotomy, and several of the arthrographic measurements. The medialization ratio (the percentage of the horizontal radius of the cartilaginous femoral head that lay medial to the Perkins line), measured at the time of the reduction, was significantly different (p < 0.04) between the hips for which the result was good or fair and those for which the result was poor. The medialization ratio averaged 75 per cent in the hips for which the result was good, 66 per cent in those for which the result was fair, and 57 per cent in those for which the result was poor. Limbus shapes 5 through 8 were associated with avascular necrosis (p < 0.05) and a poor result (p < 0.03).

Legg-Calvé-Perthes disease in girls. A comparison of the results with those seen in boys.

We reviewed the records and roentgenograms of all patients with Legg-Calvé-Perthes disease who had been seen at our institution between 1940 and 1996. One hundred and five girls (122 hips) and 470 boys (531 hips) were identified. Thus, 18 per cent of the 575 patients in the present series were girls. Seventeen (16 per cent) of the girls and sixty-one (13 per cent) of the boys had bilateral involvement. Although more girls than boys had severe involvement of the femoral head and the lateral pillar, we could not detect a significant difference between the two groups with respect to the distribution of the involvement of the hips according to the system of Catterall or the lateral pillar classification (p > 0.05, beta = 0.99). Serial roentgenograms that showed all four stages of the disease according to the system of Waldenström were available for fifty-two hips in girls and 184 hips in boys. A review of these roentgenograms revealed that the average ages of the girls at the stages of necrosis, fragmentation, reossification, and remodeling were 6.8, 7.3, 7.9, and 9.5 years, respectively, whereas the average ages of the boys were 6.8, 7.3, 7.9, and 9.9 years, respectively. Girls, however, had closure of the affected proximal femoral physis at an average age of 12.9 years, whereas boys had closure at an average age of 15.8 years. Therefore, girls had a shorter potential period for remodeling of the femoral head (average, 3.4 years) compared with boys (average, 5.9 years). Sixty-four girls (seventy-eight hips) and 363 boys (416 hips) had reached skeletal maturity by the time of the latest follow-up and were evaluated according to the system of Stulberg et al.; we could not detect a significant difference between boys and girls with respect to the distribution of the hips according to this system (p > 0.05, beta = 0.99). Although the numbers were too small for statistical analysis, our findings suggest that boys and girls who have the same Catterall or lateral pillar classification at the time of the initial evaluation can be expected to have similar outcomes according to the classification system of Stulberg et al.

Scoliosis and fibrous dysplasia of the spine.

STUDY DESIGN: This report is an account of three patients with scoliosis and polyostotic fibrous dysplasia involving the spine. The perioperative course of two patients who underwent posterior spinal arthrodesis is described. OBJECTIVES: The objective of the study was to show that extensive fibrous dysplasia of the spine and scoliosis can be treated by standard methods of posterior spinal arthrodesis with good results. SUMMARY OF BACKGROUND DATA: Scoliosis developed in three patients, and two patients underwent spinal arthrodesis. No report that discusses the results of this type of operation in this patient population exists in the literature. METHODS: Three patients with polyostotic fibrous dysplasia involving the spine and scoliosis were located at our institution. Two of the patients underwent posterior spinal arthodesis in situ; their perioperative courses are described. The course of the nonoperatively treated patient is noted briefly. RESULTS: A stable posterior spinal arthrodesis was achieved in both patients with no major complications. At the time of the last follow-up visit, both patients had radiographic evidence of a solid fusion mass with no signs of pseudarthrosis or graft resorption. Both patients currently are doing well. CONCLUSIONS: Scoliosis and its treatment has been unreported in patients with this condition, and this report demonstrates that satisfactory results can be obtained with attention to detail.

Development dysplasia of the hip from birth to six months.

The term "developmental dysplasia or dislocation of the hip" (DDH) refers to the complete spectrum of abnormalities involving the growing hip, with varied expression from dysplasia to subluxation to dislocation of the hip joint. Unlike the term "congenital dysplasia or dislocation of the hip," DDH is not restricted to congenital problems but also includes developmental problems of the hip. It is important to diagnose these conditions early to improve the results of treat- ment, decrease the risk of complications, and favorably alter the natural history. Careful history taking and physical examination in conjunction with advances in imaging techniques, such as ultrasonography, have increased the ability to diagnose and manage DDH. Use of the Pavlik harness has become the mainstay of initial treatment for the infant who has not yet begun to stand. If stable reduction cannot be obtained after 2 weeks of treatment with the Pavlik harness, alternative treatment, such as examination of the hip under general anesthesia with possible closed reduction, is indicated. If concentric reduction of the hip cannot be obtained, surgical reduction of the dislocated hip is the next step. Toward the end of the first year of life, the toddlerTs ability to stand and bear weight on the lower extremities, as well as the progressive adaptations and soft- tissue contractures associated with the dislocated hip, preclude use of the Pavlik harness.

Physeal surgery: indications and operative treatment.

The evaluation and treatment of problems that can be corrected by surgery on the growth plate have changed somewhat in recent years; therefore, it is the purpose of this article to update the reader on these advances, as well as review the basic concepts. We review the radiographic evaluation of problems in the extremities and detail key points of physeal operative techniques for correcting problems occurring with growth.

Delayed union following stress fracture of the distal fibula secondary to rotational malunion of lateral malleolar fracture.

We present a case of delayed union following stress fracture of the distal fibula secondary to rotational malunion of a lateral malleolar fracture. The patient underwent operative excision of the nonunion, plating with autogenous iliac bone grafting, and correction of the malrotation of the distal fibular fragment. The fracture healed, and the patient was asymptomatic with full range of motion at follow-up. This report documents an unusual etiology, "external malrotation," for delayed union of a fibular stress fracture.

Charcot-Marie-Tooth disease associated with hip dysplasia: a case report.

A 31-year-old woman with a known history of hip dysplasia was found to have Charcot-Marie-Tooth disease following abnormal conduction studies done at the time of surgery. Physical examination in this patient was otherwise normal, and the diagnosis of Charcot-Marie-Tooth disease had not been previously considered. This report demonstrates the importance of keeping in mind the association between hip dysplasia and Charcot-Marie-Tooth disease.