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Biomedical subjects

D S Hungerford

Publications and source records attributed to D S Hungerford.

At least 19 recordsLinked to original sources

Proinflammatory cytokine expression of IL-1beta and TNF-alpha by human osteoblast-like MG-63 cells upon exposure to silicon nitride in vitro.

This study was designed to determine the effect of Si(3)N(4) disks and particulates on human osteoblast-like MG-63 cells in vitro. The MG-63 (10(5)/mL) cells were plated onto 24-well polystyrene plates fitted with either sintered reaction-bonded (SRBSN) or reaction-bonded (RBSN) 15-mm disks. Controls consisted of wells without Si(3)N(4) disks. Cells propagated at 37 degrees C, 5% CO(2) for 48 h on Si(3)N(4) disks and control polystyrene surfaces exhibited similar proliferative capacities (7000 and 4000 cpm/10(5) cells, respectively, p > 0.05). Cells incubated with 1, 10, or 100 microgram/ml of Si(3)N(4) particles (<1.00 to 5.00 micrometer) for 24 h did not exhibit a decrease in DNA synthetic activity: 12 +/- 1.3 x 10(4), 10.5 +/- 1.5 x 10(4), and 11.0 +/- 1.7 x 10(4) cpm, respectively, compared to 11.6 +/- 2.6 x 10(4) cpm/10(5) for the control cells, as indicated by (3)H-thymidine uptake. Cells propagated on RBSN displayed increased expression of cytokines IL-1beta and TNF-alpha compared to the control cells, as shown by reverse transcriptase-polymerase chain reaction (RT-PCR). In contrast, cells propagated on SRBSN surfaces expressed the same level of IL-1beta and TNF-alpha as that of control cells. Incubation of MG-63 cells with 1-10 microgram/mL of particles did not increase IL-1beta expression. However, at 100 microgram/mL, TNF-alpha expression was greater than that of the control cells. Silicon nitride, evaluated here as disks or as particulates (1-10 microgram/mL), is biocompatible and does not hinder the proliferation or induce proinflammatory cytokine expression of human osteoblast-like MG-63 cells in vitro.

Cell Culture Techniques

Immunohistochemical evaluation of interface membranes from failed cemented and uncemented acetabular components.

Aseptic loosening of acetabular components is a primary factor compromising the long-term outcome of cemented and cementless total hip replacement. It is unknown whether the pathogenesis of the loosening process is identical for both types of fixation. The specific aim of this study was to determine whether there is a difference in the cellular and cytokine profiles of interface membranes removed from between the implant and the host bone from failed cemented (n = 5) and failed cementless acetabulae (n = 5). Routine histology and immunohistochemical evaluations were completed on each tissue specimen. The monoclonal antibodies used included those specific for cell types (macrophages, fibroblasts, T lymphocytes) and for cytokines (IL-1beta, IL-6, TNF-alpha). The patients were all revised for loosening. The time to revision was significantly longer for the cemented group (16.6 yr; 13-21 range) than for the cementless group (8.9 yr; 4-13 range). In all cases, slides from each group stained positively for each of the cell types and cytokines evaluated. Immunohistochemical analyses indicated a predominance of macrophages and ubiquitous staining for the cytokines IL-1beta and TNF-alpha within the membranes of both patient groups. The intensities of cytokine staining were similar for both patient groups. More regions of fibroblastic connective tissue were observed surrounding failed cementless components as compared to those of the cemented group. The clinical ramification of our findings is that, despite differences in the cellular composition of the periprosthetic membranes, the membranes from failed cemented and cementless implants contain cytokines, which have been shown to be capable of modulating the inflammatory response. These inflammatory mediators are likely to play a significant role in the development of osteolysis and prosthetic loosening.

Acetabulum

Effect of prosthetic titanium wear debris on mitogen-induced monocyte and lymphoid activation.

Wear debris generated by joint implant components has been reported to activate inflammatory and immune cells. Particulate debris derived from prosthetic material induces monocytes/macrophages, lymphocytes, synoviocytes, and fibroblasts to secrete cellular products, such as cytokines, which mediate inflammation. It has been speculated that degradation products impair the ability of inflammatory and immune cells to mount a protective response against noxious agents and infectious organisms by interfering with cell activation. Recent in vitro studies suggest that soluble metal ions inhibit T and B cell activation, but it is not known whether insoluble metal particles generated by prosthetic wear in tissue have the same effect. The purpose of the present study was to determine whether titanium wear debris retrieved from periprosthetic tissues surrounding a failed knee prosthesis suppresses activation of human monocytic and lymphoid cells. Peripheral blood monocytes and lymphocytes were incubated with the nonspecific activator pokeweed mitogen (PWM) in the presence or absence of titanium particles. Cell proliferative capacity and production of interleukins IL-1beta and IL-2 were determined as measures of activation. Titanium wear debris induced monocyte secretion of IL-1beta at levels comparable to those induced by PWM alone. In combination with PWM, titanium wear debris stimulated monocytes to secrete higher concentrations of IL-1beta than is stimulated by titanium itself or by PWM alone. Titanium wear debris did not activate lymphocytes, as indicated by marginal changes in DNA synthesis and IL-2 secretion, nor did it suppress the PWM-induced stimulation of DNA synthesis and IL-2 secretion. Our study suggests that nonspecific mitogen activators in spite of exposure to titanium wear debris can stimulate monocytic and lymphoid cells.

Biocompatible Materials

Variation of rotation moment arms with hip flexion.

Excessive flexion and internal rotation of the hip is a common gait abnormality among individuals with cerebral palsy. The purpose of this study was to examine the influence of hip flexion on the rotational moment arms of the hip muscles. We hypothesized that flexion of the hip would increase internal rotation moment arms and decrease external rotation moment arms of the primary hip rotators. To test this hypothesis we measured rotational moment arms of the gluteus maximus (six compartments), gluteus medius (four compartments), gluteus minimus (three compartments) iliopsoas, piriformis, quadratus femoris, obturator internus, and obturator externus. Moment arms were measured at hip flexion angles of 0, 20, 45, 60, and 90 degrees in four cadavers. A three-dimensional computer model of the hip muscles was developed and compared to the experimental measurements. The experimental results and the computer model showed that the internal rotation moment arms of some muscles increase with flexion; the external rotation moment arms of other muscles decrease, and some muscles switch from external rotation to internal rotation as the hip is flexed. This trend toward internal rotation with hip flexion was apparent in 15 of the 18 muscle compartments we examined, suggesting that excessive hip flexion may exacerbate internal rotation of the hip. The gluteus maximus was found to have a large capacity for external rotation. Enhancing the activation of the gluteus maximus, a muscle that is frequently underactive in persons with cerebral palsy, may help correct excessive flexion and internal rotation of the hip.

Biomechanical Phenomena

Clinical experience with a proximally porous-coated second-generation cementless total hip prosthesis: minimum 5-year follow-up.

This study reports the minimum 5-year follow-up of our experience with the Porous-Coated Anatomic E (PCA-E) series femoral stem and the modular acetabular cup. A total of 115 consecutive total hip replacements using PCA-E series (Howmedica, Rutherford, NJ) were performed in 108 patients. Six patients whose hips were performing well clinically died before 5-year follow-up and were excluded from the final evaluation. The remaining 109 hips (102 patients) were assessed at a mean follow-up of 72 months (range, 60-84 months). The hip diagnoses were osteoarthritis in 73, osteonecrosis in 31, rheumatoid arthritis in 2, and hip dysplasia in 3. The mean age was 56 years (range, 24-83 years). Three hips were revised: 1 because of late hematogenous infection, 1 because of aseptic loosening of the femoral component, and 1 because of postoperative loosening of an acetabular component. The Harris hip scores improved from a mean of 50 points (range, 20-66 points) preoperatively to a mean of 92 points (range, 64-100 points) at final follow-up. The score differed in each Charnley functional class, with a mean of 93 points (range, 72-100 points) in 57 hips of class A (no other joint involvement); 90 points (range, 58-100 points) in 26 hips of class B (opposite hip involvement); and 85 points (range, 37-100 points) in 26 hips of class C (multiple joint involvement or severe systemic disease). Out of 106 hips that had a full radiographic evaluation performed, 103 femoral components revealed stable bony ingrowth, 2 revealed stable fibrous ingrowth, and 1 showed migration with progressive loosening. This patient with radiographic loosening has minimal symptoms and has not required or been offered further surgery (Harris hip score of 86 points). The low aseptic loosening rate (2%) at minimum 5-year follow-up compares favorably with any cemented or cementless series. The osteolysis that was seen was focal and localized. The short follow-up does not allow determination of progression. There were no cases of distal osteolysis. We attribute the improved results from reported first-generation experience to multiple factors, including increased number of sizes (9 vs 6), increased proportional metaphyseal size, improved polyethylene manufacture (ram extruded vs machined), improved acetabular locking mechanism, and change to 26-mm from 32-mm femoral heads.

Adult

Eliminating patellofemoral complications in total knee arthroplasty: clinical and radiographic results of 121 consecutive cases using the Duracon system.

This study reports the minimum 5-year follow-up of our experience with the Duracon Total Knee Arthroplasty System. A total of 121 consecutive total knee replacements using the Duracon system (Howmedica, Rutherford, NJ) were performed in 104 patients. Three patients died before the 5-year follow-up and were excluded from the final evaluation. The remaining 118 knees (101 patients) were assessed at a mean follow-up of 65 months (range, 60-80 months). The knee diagnoses were osteoarthritis in 97 patients, rheumatoid arthritis in 2 patients, osteonecrosis in 1 patient, and pigmented villonodular synovitis in 1 patient. The mean age was 70 years (range, 28-85 years). There were no reoperations for aseptic loosening, and there have been no reoperations for patellofemoral problems. At final follow-up evaluation, 112 knees (96%) had good or excellent results, and 6 knees (4%) had poor clinical results or went on to revision. For the surviving knees, the preoperative Knee Society objective score improved from a mean of 52 points (range, 20-72 points) to a final follow-up mean of 94 points (range, 66-100 points). Five knees needed reoperations: 2 knees in 1 patient because of acute hematogenous infection at 12 months, 1 knee because of a supracondylar femur fracture, 1 because of a patellar tendon rupture, and 1 to increase polyethylene thickness because of instability. The lack of aseptic loosening at the minimum 5-year follow-up compares favorably with any cemented or cementless series of knee replacement. The almost complete absence of patellofemoral complications in this series also indicates that the design changes, with particular attention to the trochlea design and patellofemoral contact throughout full flexion, have achieved their intended purpose. The results are encouraging at midterm, awaiting true long-term (15-20 years) follow-up.

Aged

Operative management and outcome of complex wounds following total knee arthroplasty.

This study describes the treatment protocol for and the outcome of the management of complex wounds around total knee replacements. An analysis of 28 patients (29 knees) with complex defects who had surgery between January 1, 1986, and July 30, 1996, was performed. A specific management protocol was applied to each knee on the basis of the size and depth of the wound, the presence of infection, and the quality of soft tissue. Primary treatment included local wound care, debridement, and skin grafting or coverage with a fasciocutaneous flap, pedicled muscle flap, or free muscle transfer. Postoperatively, knees were evaluated using the Knee Society objective score. Successful salvage of the lower extremity was obtained in 28 knees (97 percent) and of the knee prosthesis in 24 of 29 knees (83 percent). Secondary plastic surgery procedures were necessary in five knees (17 percent), and secondary orthopedic procedures were necessary in four knees (14 percent). Successful salvage of total knee arthroplasty in the presence of a complex wound requires early identification of infection, aggressive irrigation and debridement, and early appropriate soft-tissue coverage. The use of our proposed algorithm will facilitate management of these complex wounds.

Adult

Infections associated with dental procedures in total hip arthroplasty.

Dental procedures may lead to a transient bacteraemia lasting for up to 30 minutes. Of the numerous cases of total hip arthroplasty (THA) reported which have been infected from haematogenous sources, dental procedures have been involved only infrequently. We reviewed the records of 2973 patients after THA. Of the late infections identified in 52 patients, three (6%) were strongly associated with a dental procedure. Infection was diagnosed by culture from the affected joint; Streptococcus viridans was identified in two cases and Peptostreptococcus in one. One patient had diabetes mellitus and another rheumatoid arthritis, both conditions predisposing to infection. The dental operations all lasted for more than 45 minutes and no patient received perioperative antibiotics. Infection of a THA after dental procedures is more common than has been previously suspected. Patients with systemic disease, or who are undergoing extensive procedures, should be considered for prophylactic antibiotic treatment.

Antibiotic Prophylaxis

Proximally porous-coated ingrowth prostheses: limits of use.

Callaghan has suggested that the most important factor in obtaining optimal results after total hip arthroplasty may be the ability to determine when to use cemented or cementless fixation. This article has presented the indications and relative contraindications for use of proximally porous-coated prostheses. Midterm results suggest that with appropriate patient selection, excellent clinical results can be achieved with currently available proximally porous-coated prostheses. Use of proximally coated prostheses is indicated for primary total hip arthroplasty in patients aged >70 years with good bone stock. Relative contraindications are based on interference with bone ingrowth or with the ability to achieve a congruent fit, both of which preclude establishment of rigid initial stability. These conditions include metabolic bone disease such as osteoporosis, osteomalacia, Gaucher's disease, sickle cell disorders, and Paget's disease; significant anatomical distortion, as seen in developmental dysplasia of the hip with anteversion, prior osteotomy, or intertrochanteric fracture; Dorr type C bone; and current treatment with radiation, chemotherapy, indomethacin, or diphosphonates. The same relative contraindications to use are applicable in revision situations. Further, proximally porous-coated prostheses should not be used for revision arthroplasty in the setting of massive bone loss, limited life expectancy, or inability to participate in protected weight bearing. These devices may be used successfully in revision arthroplasty when the hip has minimal or moderate bone loss, and occasionally in the setting of severe bone loss. As further information is revealed through the long-term (10-20 years) results of proximally coated prostheses, further refinements and knowledge of the indications and contraindications for the use of these prostheses will be revealed.

Arthroplasty, Replacement, Hip

Patellofemoral complications after total knee arthroplasty: a comparison of Modular Porous-Coated Anatomic with Duracon prostheses.

Clinical and radiographic analyses were used to compare results obtained in 45 patients who underwent a Modular Porous-Coated Anatomic total knee arthroplasty with results in a similar group of 45 patients who underwent a Duracon total knee arthroplasty. The surgeries were consecutively performed over an 8-month period, and follow-up evaluation averaged 63 months. The two patient groups were similar with regard to the following variables: age, sex, diagnosis, height, weight, and preoperative and postoperative activity levels. Whereas both Duracon and Modular total knee arthroplasty prostheses yielded similar results approximately 5 years after surgery, the data suggest that Duracon appears to minimize patellofemoral complications.

Adult

Infected total knee arthroplasty treated with arthrodesis using a modular nail.

Failed treatment of infected total knee replacement presents few attractive surgical options. Knee arthrodesis is challenging surgically and can be complicated by nonunion, malunion, or recurrent infection. Recently, a modular titanium intramedullary nail has been used in an attempt to reduce the incidence of nonunion and the rate of complications. In the present study, a review of the results of knee arthrodesis after infected total knee arthroplasty in 21 patients at three large academic institutions was performed. All patients were followed up for a mean of 2.4 years (range, 2-7.5 years). The mean age of the patients was 64 years. The mean number of previous operations was four (range, 2-9 operations). A solid arthrodesis was achieved without additional surgical treatment in 20 of 21 patients (95%). The mean time to fusion was 6.3 months. The one patient who suffered a nonunion achieved fusion after a subsequent bone grafting procedure. Based on the present study, intramedullary arthrodesis with a coupled titanium nail, is a reliable, effective method of achieving fusion after infection of a total knee arthroplasty. This procedure resulted in a high rate of fusion and a lower rate of complications when compared with traditional methods of arthrodesis.

Aged

Pathologic features in steroid and nonsteroid associated osteonecrosis.

Multiple pathophysiologies for osteonecrosis have been postulated and various associated risk factors defined for this disease. However, the pathologic findings of the end stage disease are thought to be similar in all patients. To the author's knowledge, there are no data in the literature comparing the pathologic characteristics of osteonecrosis in a quantitative manner between groups of patients with different associated risk factors. The current study examined the pathologic features of core decompression specimens from the femoral head in a group of patients with osteonecrosis associated with corticosteroid therapy and compared them with specimens from patients with osteonecrosis with no history of corticosteroid therapy. The study group comprised 65 patients (96 hips); 45 patients (68 hips) in the corticosteroid group and 20 patients (28 hips) in the noncorticosteroid group. In the corticosteroid group, 65% of dead bone was identified histologically (44 of 68) as compared with 46% (13 of 28) in the noncorticosteroid group. Specimens staged according to the histologic grading system of Arlet and Durroux revealed the corticosteroid group had a higher incidence of late stage lesions than did the noncorticosteroid group. This was found even though the two groups had similar radiographic staging distribution. The hips in patients who used alcohol were comparable pathologically to the hips in patients who used corticosteroids. This study emphasizes that the histologic features of necrosis and repair are similar in corticosteroid and noncorticosteroid osteonecrosis. However, there were differences in the distribution of viable bone and pathologic stage of the lesions in the two groups, suggesting a more rapid evolution of changes in the corticosteroid group.

Adult

Effect of particulate bioactive glass on human synoviocyte cultures.

Bioglass is a resorbable glass material that has been shown to induce osteoblast proliferation as well as bone matrix production in vitro. Its physico-chemical properties have been reported to be suitable for use as an implant coating for arthroplasty. However, Bioglass is a ceramic material that can fragment into particulate debris in vivo. The effect of particulate Bioglass on tissue cells has not been defined. In order to determine the biologic response to particulate Bioglass, we tested its effect on human synoviocytes in a cell culture model. At the concentrations of 1.0 and 10, micrograms/mL, particulate Bioglass (sizes ranging from approximately 0.5 to 80 microns) had a low cytotoxic effect. However, these concentrations induced secretion of TNF alpha. The observation that particulate Bioglass elicits release of inflammatory cytokines suggests that the development of this bioceramic implant coating should address techniques that would minimize the generation of particulates.

Biocompatible Materials

Radiographic predictors of outcome of core decompression for hips with osteonecrosis stage III.

Various investigators have studied the prognostic influence of various demographic, laboratory, and radiographic parameters on outcome for different treatment methods for osteonecrosis of the femoral head. A cross sectional study was done of 52 patients (68 hips) who had a core decompression for Ficat and Arlet Stage III osteonecrosis of the femoral head. The purpose of this study was to evaluate the prognostic significance of various radiographic factors for risk of disease progression after treatment with core decompression. Radiographic parameters included Steinberg stages (III or IV), Ohzono stage (central or lateral location), amount of head depression, extent of crescent sign arc, and extent of lesion by Kerboul combined necrotic angle measurements. Patient outcome assessment was at a followup mean of 12 years (range, 4-18 years) after core decompression. Overall, 20 of the 68 hips (29%) had satisfactory outcomes. Of the 44 hips with Steinberg Stage III disease, 18 (41%) underwent total hip arthroplasty. In comparison, in the Steinberg Stage IV hips, 22 of 24 hips (92%) underwent arthroplasty. Ohzono Stage B lesions had 50% survival (eight of 16 hips) compared with 23% survival (12 of 52 hips) for Ohzono Stage C. Hips with combined necrotic angles greater than 250 degrees had 16% survival (seven of 45) which can be compared with 57% survival (13 of 23) for hips with angles less than 250 degrees. The best multiple regression model for a satisfactory outcome was a Steinberg Stage III hip (no head depression), a central lesion (Ohzono Stage B), and a small lesion (< 250 degrees combined necrotic angle). With this combination, there were 89% satisfactory outcomes (8 of 9 hips). Conversely, the best generalized linear model for unsatisfactory outcomes (0 hips surviving of 14) was Steinberg Stage IV disease (head depression), lateral location (Ohzono Stage C lesion), and a large extent of the lesion (> 250 degrees combined necrotic angle).

Adult