Immunoglobulin heavy chain variable region gene replacement As a mechanism for receptor revision in rheumatoid arthritis synovial tissue B lymphocytes.

Mature B cells can alter their antibody repertoires by several mechanisms, including immunoglobulin heavy chain variable region (V(H)) replacement. This process changes the antigen combining site by replacing a portion of the original V(H)/diversity/heavy chain joining region (V(H)DJ(H)) rearrangement with a corresponding portion of a new V(H) segment. This exchange can involve cryptic heptamer-like sequences embedded in the coding regions of V(H) genes. While studying the B lymphocytes that expand in the synovial tissues of patients with rheumatoid arthritis (RA), clones with V(H)DJ(H) variants that were apparently generated by V(H) replacement were identified with surprising frequency (approximately 8%). Examples of multiple independent V(H) replacement events occurring in distinct progeny clones were also identified. These secondary V(H) rearrangements were documented at both the cDNA and genomic DNA levels and involved several heptamer-like sequences at four distinct locations within V(H) (three sites in framework region 3 and one in complementarity determining region 2). The identification of blunt-ended double-stranded DNA breaks at the embedded heptamers and the demonstration of recombinase activating gene (RAG) expression suggested that these rearrangements could occur in the synovial tissues, presumably in pseudo-germinal centers, and that they could be mediated by RAG in a recognition signal sequence-specific manner. The presence of V(H) mutations in the clones that had undergone replacement indicated that these B cells were immunocompetent and could receive and respond to diversification signals. A relationship between these secondary V(H) gene rearrangements and the autoimmunity characteristic of RA should be considered.

Clonal expansion is a characteristic feature of the B-cell repetoire of patients with rheumatoid arthritis.

The present study was designed to analyze the level of B-cell clonal diversity in patients with rheumatoid arthritis by using HCDR3 (third complementarity determining region of the rearranged heavy chain variable region gene) length as a marker. A modified immunoglobulin VH gene fingerprinting method using either genomic DNA or complementary (c)DNA derived from B cells of the peripheral blood, synovial fluid, and tissues of several rheumatoid arthritis patients was employed. These assays permitted the detection and distinction of numerically expanded B-cell clones from activated but not numerically expanded B-cell clones. The present data suggest that B-cell clonal expansion is a common and characteristic feature of rheumatoid arthritis and that it occurs with increasing frequency from the blood to the synovial compartments, resulting in a narrowing of the clonal repertoire at the synovial level. These clonal expansions can involve resting, apparently memory B cells, as well as activated B cells. Furthermore, some of these individual expansions can persist over extended periods of time. These findings support the hypothesis that a chronic ongoing (auto)immune reaction is operative in rheumatoid arthritis and that this reaction, at least at the B-cell level, may be unique to each individual joint. A determination of the targets of these autoimmune reactions may provide valuable clues to help understand the immunopathogenesis of this disease

Cancellous bone screw thread design and holding power.

This study was designed to isolate and evaluate the parameters of host density, outer diameter (OD), root diameter (RD), and pitch in cancellous bone screw design and their effect on holding power. Special emphasis was placed on screw pitch, which has been evaluated infrequently in the literature. Three groups of stainless steel V thread screws (group I, OD 4.5 mm, RD 3.0 mm; group II, OD 6.4 mm, RD 3.5 mm; group III, OD 6.4 mm, RD 4.2 mm) were machined with progressive increases in pitch from 12 to 32 threads per inch (TPI). Two densities of synthetic cancellous bone material (Pedilen, Ottobock, Minneapolis, MN, U.S.A.), 0.15 g/ml and 0.22 g/ml, were then prepared and molded into sheets 1.9 cm thick and the screw threads completely engaged. Push-out tests were performed using a servohydraulic testing machine (MTS, Minneapolis, MN, U.S.A.). Fifteen trials of each screw were tested in each material. The effect on holding power of the different parameters of the custom screws in order of importance was (a) host material density, (b) OD (c) pitch, and (d) RD. The groups with a 6.4-mm OD had a much greater holding power than did the group with a 4.5-mm OD (p < 0.001). A decrease in screw pitch (increased threads per inch) did itself have a significant improved effect on fixation for all groups in both pedilen densities (p < 0.001). In the two 6.4-mm screw groups studied, the difference in the two root diameters (4.2 mm vs. 3.5 mm) showed the smaller root diameter to give a greater holding power in the less dense 0.15 g/ml pedilen (p < 0.001). In the more dense 0.22 g/ml pedilen there was no difference (p = 0.26) between the root diameters. To optimize holding power, cancellous screws may be designed with a decreased pitch (increased TPI) over those commercially available today. Cannulated screws must have a larger cancellous thread root diameter to leave room for the central cannulation; this may decrease their holding power in less dense cancellous bone but not in denser bone.

Intracapsular fractures of the femoral neck. Results of cannulated screw fixation.

The results of stabilization of an intracapsular fracture of the femoral neck with cannulated screws placed in parallel in 141 patients between 1980 and 1985 were reviewed retrospectively. Fifty patients (35 per cent) had a non-displaced fracture (Garden Stage I or II) and ninety-one (65 per cent) had a displaced fracture (Garden Stage III or IV). The median age of the patients was sixty-eight years (range, twenty-four to ninety-five years). The mean duration of follow-up was eight years. No patient died or had a wound infection during the stay in the hospital. Twenty-nine patients, who had a median age of seventy-five years (range, fifty-six to ninety-five years), died within sixty months after treatment; eleven of them (median age, seventy-five years [range, sixty-five to eighty-six years]) died within the first twelve months. There was a loss of position or a non-union of the fracture in five patients (4 per cent) and healing of the fracture in 136 patients (96 per cent). Thirteen patients (11 +/- 3 per cent) had histological or roentgenographic evidence of osteonecrosis within twenty-four months after treatment. Ten of these patients had had a displaced fracture. Osteonecrosis developed in thirteen additional patients during the remaining period of follow-up. Eight of these patients had had a displaced fracture. The prevalence of osteonecrosis at the time of the most recent follow-up (mean duration, eight years) was 22 +/- 4 per cent. Osteonecrosis developed in eight of the forty-one patients who had had a Garden Stage-II fracture, in six of the thirty patients who had had a Garden Stage-III fracture, and in twelve of the forty patients who had had a Garden Stage-IV fracture. The fifty-five surviving patients in whom the fracture healed without complications were found to be functioning well more than sixty months after the fracture.

Fatigue testing of cerclage stainless steel wire fixation.

Because wire fixation continues to be used extensively in the practice of orthopaedic surgery, despite a high incidence of wire breakage, understanding the mechanism of this failure is of important clinical interest. The aim of this study was to investigate the failure of cerclage stainless steel wire using an in vitro cyclic loading device. A stainless steel testing fixture consisting of two half cylinders with a combined diameter of 2.5 cm was mounted in a servo hydraulic testing machine. Specimens of number 18 gauge (0.97 mm diameter) and number 16 gauge (1.22 mm diameter) 316L stainless steel wire were mounted around the two half cylinders in a cerclage manner using three different fastening methods: a uniform symmetrical twist, a knot twist, and a square knot. Single-load-to-failure and cyclic load tests were performed under controlled tensile displacement. The cerclage wire system fastened with a twist resulted in failure at loads significantly lower than systems fastened with the knot twist and the square knot. Cyclic loading of the wire fastened with twists also showed decreased fatigue properties when compared to those fastened with the knot twist and the square knot. In all tests, the 16-gauge wire was found to be clearly superior to the 18-gauge wire. For both wires, fatigue strengths at 100,000 cycles were only 30-37% of the static ultimate strength. These results show that wire diameter and fastening system are two important factors affecting the mechanical properties of the resulting fixation.

Magnetic resonance imaging of the hip after displaced femoral neck fractures.

This study was designed to determine the sensitivity of magnetic resonance imaging (MRI) in the detection of ischemia or avascular necrosis after displaced intracapsular hip fractures. Magnetic resonance imaging was performed on 20 patients who had hemiarthroplasties performed for Garden IV intracapsular fractures. Sixteen patients had in vivo coronal T1-weighted spin-echo imaging from the day of injury to 60 days after fracture. After hemiarthroplasty, all 20 resected femoral heads had in vitro T1 imaging. A coronal slab was then cut from the center of the femoral head and studied histologically. The in vivo, in vitro, and histologic slides correlated well. None of the MRI images depicted areas of ischemia or avascular necrosis in patterns observed in nontraumatic necrosis. Avascular bone can be indistinguishable from normal bone in both MRI and histologic sections for a considerable amount of time after vascular insult. Magnetic resonance imaging is not a prognosticator for posttraumatic osteonecrosis in the first two weeks after fracture.

Diagnosis of occult fractures about the hip. Magnetic resonance imaging compared with bone-scanning.

Sixty-two consecutively seen patients in whom a fracture about the hip was clinically suspected, but in whom the radiographic findings were negative, were examined with both magnetic resonance imaging and bone-scanning. The magnetic resonance-imaging studies, consisting of T1-weighted coronal sections, were done within twenty-four hours after admission to the hospital, and the bone scans, within seventy-two hours after admission. There were twenty-three men and thirty-nine women. Thirty-six patients who had evidence of a fracture on the magnetic resonance-imaging study also had a positive bone scan initially. Twenty-three patients who had a negative finding on the magnetic resonance-imaging study had a corresponding negative bone scan. Two additional patients had evidence of avascular necrosis of the femoral head on both the magnetic resonance image and the bone scan, and they were managed non-operatively. One patient had a positive magnetic resonance image and a negative bone scan twenty-four hours after admission. A repeat bone scan, which was made six days later, was positive for a fracture of the femoral neck and the patient was managed with internal fixation. Magnetic resonance imaging was as accurate as bone-scanning in the assessment of occult fractures of the hip. The magnetic resonance imaging took less than fifteen minutes to perform, and it was tolerated well by the patient. Magnetic resonance imaging provides an early diagnosis of occult fractures about the hip and may decrease the length of the stay in the hospital by expediting definitive treatment.

Short crank cycle ergometry.

The change in knee angle during cycling was mathematically analyzed. It was determined that if the crank length of the cycle ergometer was shortened, the arc of knee motion necessary to cycle could be reduced. A computer program was written to represent the above mathematical model utilizing a patient's lower limb lengths to generate an individualized, range of motion profile. A custom cycle ergometer was built with interchangeable crank lengths of 80 mm, 110 mm, 140 mm, and 170 mm. This device can be adjusted to achieve a desired range of motion for a specific patient. The above custom cycle ergometer can be used on early postoperative knee patients who are unable to ride a conventional cycle ergometer because of a lack of knee motion or on patients who require a limited arc of motion in their postoperative therapy protocol. J Orthop Sports Phys Ther 1991;13(2):95-100.

Sciatic neuropathy secondary to migration of trochanteric wire following total hip arthroplasty.

Delayed sciatic neuropathy secondary to migration of a free segment of trochanteric wire in an otherwise successful total hip arthroplasty seems not to have been reported previously. A 60-year-old woman with a total hip arthroplasty with a lateral transtrochanteric approach had the trochanter reattached with two 18-gauge Vitallium wires. The osteotomy healed uneventfully despite a break in the vertical wire ten days after surgery. Five years and ten months later, the patient began to have severe sciatic pain. Roentgenograms showed a free fragment of trochanteric wire posterior to the hip joint. On exploration, the 2-cm wire fragment was found to lie entirely within the epineurium of the sciatic nerve.

Anterior decompression and stabilization with methylmethacrylate and a bone bolt for treatment of pathologic fractures of the cervical spine. A report of two cases.

A 48-year-old woman and a 61-year-old man were treated for pathologic fractures of the cervical vertebral bodies that caused neurologic defect. In both patients an anterior decompression was performed with the removal of the diseased vertebrae. Immediate stability was obtained with a bone bolt imbedded in methylmethyacrylate. Both patients are functioning satisfactorily without any external support of the cervical spine four years and one and one-half years after their respective operations. This method is applicable only in carefully selected cases.

Scintimetric evaluation of complications after femoral neck fractures.

The primary surgical approach to the femoral neck fracture should be one with the lowest mortality and morbidity. Internal fixation appears to be the safe and logical approach for most of the reducible intracapsular fractures. Careful follow-up of these patients then is important. 85Sr scintimetry is a simple and accurate method in the early detection and evaluation of secondary complications in these patients. The 85Sr scintimetric pattern in the normal healing process was defined in relation to time interval after the fracture. At any time after 4 months following fracture, those hips destined for osteonecrosis, with or without non-union, showed significantly more radionuclide uptake over the femoral head than those hips which healed normally. In non-union there was a trend toward increased counts over the fracture site during 6 to 18 months after fracture, but no such tendency was noted in other periods.

Further observations on 85Sr scintimetry in intracapsular fracture of the hip.

Sixty-seven hip joints with intracapsular fracture and the 67 opposite, normal hip joints were studied with 85Sr scintimetry from two weeks to six years after fracture. Consistently, fractures that developed osteonecrosis showed extremely high counts at the fracture site and the femoral head; fractures that failed to unite also showed extremely high counts at the fracture site and somewhat lower counts in the femoral head; fractures that were healing normally showed counts at the fracture site that were higher than those of the normal, uninjured hip but lower than those at fracture sites where osteonecrosis or nonunion was present. Prediction of complications by 85Sr scintimetry is not reliable within the first few months on injury; thereafter, however, the procedure has definite diagnostic value, particularly for osteonecrosis.