Dissociation of intracellular lysosomal rupture from the cell death caused by silica.

The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388d(1) macrophages. After 3 h of exposure to 150 mug silica in medium containing 1.8 mM Ca(2+), 60 percent of the cells were unable to exclude trypan blue. In the absence of extracellular Ca(2+), however, all of the cells remained viable. Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca(2+). The percentage of P388D(1) cells killed by silica depended on the dose and the concentration of Ca(2+) in the medium. Intracellular lyosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase. With either assay, 60 percent of the cells exposed to 150 mug silica for 3 h in the presence of Ca(2+) showed intracellular lysosomal rupture, was not associated with measureable degradation of total DNA, RNA, protein, or phospholipids or accelerated turnover of exogenous horseradish peroxidase. Pretreatment with promethazine (20 mug/ml) protected 80 percent of P388D(1) macrophages against silica toxicity although lysosomal rupture occurred in 60-70 percent of the cells. Intracellular lysosomal rupture was prevented in 80 percent of the cells by pretreatment with indomethacin (5 x 10(-5)M), yet 40-50 percent of the cells died after 3 h of exposure to 150 mug silica in 1.8 mM extracellular Ca(2+). The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98 percent of the cells treated for 1 h in either the presence or absence of extracellular Ca(2+). With the addition of 1.8 mM Ca(2+), 80 percent of the cells was killed after 3 h, whereas all of the cells remained viable in the absence of Ca(2+). These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death cause by silica or A23187. Cell death is dependent on extracellular Ca(2+) and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins.

Glucocorticoids decrease interleukin-6 levels and induce mineralization of cultured osteogenic cells from children with fibrous dysplasia.

Fibrous dysplasia (FD) is a progressive bone disease in which abnormal fibroblast proliferation results in the replacement of normal cancellous bone with an immature fibrous tissue that is poorly mineralized. The disease manifests itself in the monostotic form in which only one bone is involved and the polyostotic form in which multiple bones at different sites are affected. The McCune-Albright syndrome is a variation of the polyostotic form in which patients demonstrate a greater extent of bone involvement and a variety of endocrinopathies. Somatic activating mutations in the GNAS gene have been demonstrated in the fibrotic lesions of patients affected with either monostotic or polyostotic FD. The increased cAMP levels caused by the G-protein mutations lead to increased interleukin-6 (IL-6) levels in the affected tissues, resulting in abnormal osteoblast differentiation and increased osteoclastic activity. Utilizing cell culture techniques that have been developed for mammalian bone marrow stromal cells, we have successfully cultured osteogenic stem cells from the affected stroma of 11 FD patients. Cells cultured from patients with polyostotic FD showed a high frequency of the Gsalpha mutation, whereas cells from monostotic FD patients showed a low frequency of the mutation. Both the normal and FD cells displayed the osteogenic phenotype when exposed to medium containing glucocorticoids. Glucocorticoids also caused a dramatic inhibition of IL-6 mRNA and protein levels in osteogenic cells cultured from the FD patients. These findings suggest that chemical alteration of cellular function may lead to new treatment options for patients with FD.

Reflex sympathetic dystrophy in children. A physical therapy approach.

Children with reflex sympathetic dystrophy (RSD) almost always receive physical therapy as part of a multidisciplinary approach, but there is controversy about the efficacy of many alternative modalities. In a retrospective chart review of 24 females and 12 males with 49 episodes of RSD (mean age at onset, 13.4 years), the average time to correct diagnosis was 9.4 months (median, 4.2 months; range, 1-53 months). Sixteen ankles, 12 knees, eight wrists, two hips, and two shoulders were involved. Psychological assessments revealed significant abnormalities in 25 (83%) of 30 children evaluated. Thirty-four (94%) of 36 children received physical therapy including a wide variety of nonstandardized approaches. Children with one to two episodes of RSD averaged 4.0 physical therapy modalities; unresolved cases had 8.9 modalities attempted. Time from the first RSD episode to resolution averaged 9.0 months in 69% of children. Incorrect diagnoses prolonged many initial episodes; following correct diagnosis, symptom resolution occurred in 3.1 months. Recurrences are common, and 25% of children still exhibited RSD symptoms at last follow-up.

Function of the upper extremities in hereditary multiple exostoses.

The radiographic anatomy, functional status, and impairment ratings of twenty-eight patients (fifty-six extremities) who had hereditary multiple exostoses were evaluated. The patient (or the parent) also subjectively graded the function of each extremity with use of a standard rating-assessment tool. Degenerative joint disease was evident in three (5 per cent) of the fifty-six extremities at the time of follow-up, when the patients were an average of twenty-one years old. With use of the hand test of Jebsen et al., the average score was in the forty-seventh percentile for the dominant extremity and in the twenty-eighth percentile for the non-dominant extremity. Loss of pronation and supination increased with increasing age. Dislocation of the radial head was significantly associated with negative ulnar variance (p=0.008) and with the impairment rating (p=0.001), but not with the subjective score or with the performance on the hand test of Jebsen et al. So-called whole-person impairment ratings ranged from 0 to 17 per cent (average, 5 per cent). It has been our experience that deformities of the upper extremity in patients who have hereditary multiple exostoses are well tolerated and lead to little loss of function as measured both subjectively and objectively.

Prior deposition of autologous blood in elective orthopaedic surgery.

We retrospectively analyzed a program of prior deposit and storage of autologous blood that was used for patients who underwent elective orthopaedic procedures over a period of thirty-six months at the Walter Reed Army Medical Center. Of a total of 211 patients who underwent total joint replacement or spinal fusion during this period and who had sufficient records to be included in the study, a total of 159 patients enrolled in the program. The fifty-two patients who did not enroll in the study, twelve of whom were rejected because of medical problems, served as a control group. Since the preoperative hematocrit values for patients in the group that received autologous blood were similar to those for the control group, multiple preoperative phlebotomies in these patients, who had received supplemental iron, did not seem to have any deleterious effects. One hundred and thirteen (71 per cent) of the 159 patients who were enrolled in the program received only autologous blood. The remaining forty-six patients required homologous blood also, but 64 per cent of their transfusion needs were provided by autologous blood. The only reactions to the transfusions in the study were in four patients who received homologous blood. We think that a program of prior deposit and storage of autologous blood should be an option for patients who are to undergo elective orthopaedic surgery. Such a program is well tolerated by the patients and easily managed by the staff, and it was not difficult to implement at our tertiary referral hospital.

Unicameral bone cysts treated by injection of bone marrow or methylprednisolone.

In 79 consecutive patients with unicameral bone cysts we compared the results of aspiration and injection of bone marrow with those of aspiration and injection of steroid. All were treated by the same protocol. The only difference was the substance injected into the cysts. The mean radiological follow-up to detect activity in the cyst was 44 months (12 to 108). Of the 79 patients, 14 received a total of 27 injections of bone marrow and 65 a total of 99 injections of steroid. Repeated injections were required in 57% of patients after bone marrow had been used and in 49% after steroid. No complications were noted in either group. In this series no advantage could be shown for the use of autogenous injection of bone marrow compared with injection of steroid in the management of unicameral bone cysts.

A review of Morquio syndrome.

Morquio syndrome is one of the mucopolysaccharidoses. Glycosaminoglycans accumulate within the cells, leading to many systemic alterations. Alterations in connective tissue and cartilage ground substance result in abnormal formation and growth of the skeletal system. The major orthopedic manifestations include shortening of the trunk and limbs, spinal curvature, odontoid hypoplasia with upper cervical instability, and lower-limb alignment problems. The management of the orthopedic manifestations of this syndrome requires a broader knowledge of the genetic, metabolic, and systemic effects of the metabolic alterations.

A 13-month-old boy with progressive genu valgum.

The following case illustrates the roentgenographic and clinical findings of a condition of interest to the orthopedic surgeon. Initial history, physical findings, and roentgenographic examinations are indicated below. The final clinical and differential diagnoses are presented on the following pages.

Closure of the physis after pinning of slipped capital femoral epiphysis.

A study was conducted to determine what effect pinning in situ for slipped capital femoral epiphysis (SCFE) had on the timing of subsequent closure of the growth plate. Eighty-nine patients with a SCFE were reviewed. Twenty-six patients with a unilateral SCFE were treated with closed pinning in situ; no manipulative reductions were performed. The timing of physeal closure was assessed using postoperative radiographs of both pinned and non-pinned sides. The average time until physeal closure was 12.0 months for the pinned physis and 22.2 months for the non-pinned physis. In two cases, the physes closed simultaneously, and in no patient did the non-pinned physis close earlier than the pinned physis. The pinned physes closed an average of 10.2 months (range: 0 to 22) earlier than the unpinned physes. No difference was noted in the rates of closure with different types of internal fixation. This study supports the theory that pinning SCFE in situ causes early closure of the physis.

Fibrous dysplasia.

Fibrous dysplasia provides the orthopedic surgeon with tremendous reconstructive challenges. The manifestations of the condition are very diverse and often involve organ systems not routinely cared for by the orthopedic surgeon. We present a concise review of the radiography, histology, clinical manifestations, and complications of this condition, with the main focus on the non-orthopedic management challenges.

Treatment options in unicameral bone cysts.

Curettage and bone grafting has been the traditional treatment for unicameral bone cysts. Aspiration followed by injection of methylprednisolone acetate has been successfully used by Scaglietti et al. We reviewed 59 patients treated for unicameral bone cysts. The patients were subsequently evaluated for healing with regard to age, activity of cyst, and bone graft origin. The healing rate for curettage and bone graft was 53%. For patients with methylprednisolone acetate injection after aspiration, the healing rate was 70%. This difference was not statistically significant. The methylprednisolone acetate injection method has comparable efficacy to that of the more traditional curettage and bone graft method, and it is safe and cost-effective.

Reflex sympathetic dystrophy in children: an orthopedic perspective.

To design diagnostic criteria for reflex sympathetic dystrophy (RSD) and to initiate a prospective treatment protocol, we reviewed our experience with 49 episodes of RSD in 36 children. There were 24 females and 12 males; mean age at diagnosis was 13.4 years (range: 8 to 19); mean time from pain onset to correct diagnosis was 9.2 months (range: 1 to 53). Lower extremity involvement predominated. Pain was "severe" in 61%, and skin color changes, swelling, hyperesthesia, abnormal skin temperatures, muscle weakness, and decreased range of motion were all present in at least 75% of cases. Osteopenia was observed in 15 of 38 radiographs; of 24 bone scans, 7 were normal, 11 showed increased uptake, and 6 demonstrated decreased uptake. Of the 23 children who had psychological evaluations, 83% revealed some type of significant emotional dysfunction. Analgesic and antiinflammatory medications were not helpful, nor were local injections or regional blockades effective. An inpatient diagnostic and rehabilitation program for treating chronic pain, including orthopedics, rheumatology, psychology, and twice-daily physical therapy was most likely to lead to resumption of age-appropriate activities. Despite extensive physiological testing, physician, parent, and/or patient reluctance to accept absence of a primary organic disease was common. We present diagnostic criteria for pediatric RSD.

Scoliosis evaluation and management.

Specific guidelines for the management of scoliosis must be individualized based on a number of factors. It is important to be sure that a patient who appears to have ordinary idiopathic scoliosis does not have some underlying disease process or congenital anomaly, which if undiscovered, may complicate that patient's management. The management of scoliosis has changed in the past few years due to significant advances in blood banking, anesthesia, and spinal instrumentation. Scoliosis fusions are performed regularly throughout the country with a great degree of safety. By combining early detection and modern management techniques, significant untreated curvature of the spine can be eliminated, and functional and cosmetic deformity can be avoided.

Surgical treatment of adolescent hallux valgus.

Surgical for adolescent hallux valgus (HV) was performed on 32 feet. Five feet (16%) required revision surgery, and technical errors accounted for recurrence in all five. Satisfaction was obtained in 70% of patients. According to a new bunion rating score, 59% of patients had good to excellent results. In a subgroup of patients treated with metatarsal osteotomy for metatarsus primus varus, the Mitchell osteotomy provided an excellent rating in 95% of patients. Surgery for adolescent HV provides satisfying results in most patients. The one factor most highly correlated with both decreased risk of recurrence of angular deformity and patient satisfaction was a reduction of the intermetatarsal (IM) angle.

Computed tomography for early evaluation of developmental dysplasia of the hip.

Computed tomography (CT) provides an axial image of the dysplastic hip. We reviewed 130 CT scans performed after closed reduction for developmental dysplasia of the hip (DDH) in 42 patients (52 hips). We evaluated methods of measuring CT scans and found no described measurement that was predictive of development of avascular necrosis (AVN) or persistent acetabular dysplasia. The CT scan provides an excellent image of the infant hip when the child is in a spica cast and is useful to confirm an adequate reduction. No patient in this series lost reduction after 2 weeks.

Acute arthritis of the hip in a child infected with the Lyme spirochete.

Acute Lyme arthritis may mimic acute pyogenic arthritis. Although the arthritis associated with infection with the spirochete, Borrelia burgdorferi, is more commonly seen in the chronic stage (Stage III) of the disease, occasionally it may present as the initial clinical manifestation. A five-year-old girl with acute arthritis of the hip is reported to discuss classification and management of arthritis associated with Lyme disease.

Chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis is a rare entity that is easily confused with pyogenic osteomyelitis. Three cases that illustrate the common modes of presentation and roentgenographic findings are presented. The current orthopaedic literature is reviewed, and management guidelines are discussed.