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Biomedical subjects

R D Foster

Publications and source records attributed to R D Foster.

At least 19 recordsLinked to original sources

Mixed allogeneic chimerism as a reliable model for composite tissue allograft tolerance induction across major and minor histocompatibility barriers.

BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting may be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a major MHC mismatch without the need for long-term immunosuppression. METHODS: Mixed allogeneic chimeras were prepared by using rat strains with strong MHC incompatibility [WF (RT1Au), ACI (RT1Aa)] WF + ACI-->WF, n=23. The bone marrow (BM) of recipient animals was pretreated with low-dose irradiation (500-700 cGy), followed by reconstitution with a mixture of T cell-depleted syngeneic (WF) and allogeneic (ACI) cells. Additionally, the recipient animals received a single dose of anti-lymphocyte serum (10 mg) 5 days before bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day before BMT to 10 days post-BMT. Hindlimb transplants were performed 12 months after BMT. Five animals received a limb allograft irradiated (1000 cGy) just before transplantation. Rat chimeras were characterized (percentage of donor cells present within the bloodstream) by flow cytometry at 3 and 12 months after BM reconstitution and after hindlimb transplantation. RESULTS: Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 18/23 animals. Multi-lineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60% (n=18) no sign of limb rejection was present for the duration of the study. All animals with chimerism <20% (n=5) developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) developed at >60 days in 14/21 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n=10). Five out of five animals with irradiated limb transplants showed no sign of GVHD at >100 days. CONCLUSIONS: Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. Partial functional return should be expected. The BM transplanted as part of the hindlimb allograft plays a role in the etiology of GVHD. Manipulating that BM before transplantation may influence the incidence of GVHD. This represents the first reliable rat hindlimb model demonstrating rejection-free CTA survival in an adult animal across a major MHC mismatch without the long-term need for immunosuppressive agents.

Animals↗

Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children.

Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms. The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance. Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi. Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.

Brain↗

Complex abdominal wall reconstruction: a comparison of flap and mesh closure.

OBJECTIVE: To analyze a series of patients treated for recurrent or chronic abdominal wall hernias and determine a treatment protocol for defect reconstruction. SUMMARY BACKGROUND DATA: Complex or recurrent abdominal wall defects may be the result of a failed prior attempt at closure, trauma, infection, radiation necrosis, or tumor resection. The use of prosthetic mesh as a fascial substitute or reinforcement has been widely reported. In wounds with unstable soft tissue coverage, however, the use of prosthetic mesh poses an increased risk for extrusion or infection, and vascularized autogenous tissue may be required to achieve herniorrhaphy and stable coverage. METHODS: Patients undergoing abdominal wall reconstruction for 106 recurrent or complex defects (104 patients) were retrospectively analyzed. For each patient, hernia etiology, size and location, average time present, technique of reconstruction, and postoperative results, including recurrence and complication rates, were reviewed. Patients were divided into two groups based on defect components: Type I defects with intact or stable skin coverage over hernia defect, and Type II defects with unstable or absent skin coverage over hernia defect. The defects were also assigned to one of the following zones based on primary defect location to assist in the selection and evaluation of their treatment: Zone 1A, upper midline; Zone IB, lower midline; Zone 2, upper quadrant; Zone 3, lower quadrant. RESULTS: A majority of the defects (68%) were incisional hernias. Of 50 Type I defects, 10 (20%) were repaired directly, 28 (56%) were repaired with mesh only, and 12 (24%) required flap reconstruction. For the 56 Type II defects reconstructed, flaps were used in the majority of patients (n = 48; 80%). The overall complication and recurrence rates for the series were 29% and 8%, respectively. CONCLUSIONS: For Type I hernias with stable skin coverage, intraperitoneal placement of Prolene mesh is preferred, and has not been associated with visceral complications or failure of hernia repair. For Type II defects, the use of flaps is advisable, with tensor fascia lata representing the flap of choice, particularly in the lower abdomen. Rectus advancement procedures may be used for well-selected midline defects of either type. The concept of tissue expansion to increase both the fascial dimensions of the flap and zones safely reached by flap transposition is introduced. Overall failure is often is due to primary closure under tension, extraperitoneal placement of mesh, flap use for inappropriate zone, or technical error in flap use. With use of the proposed algorithm based on defect analysis and location, abdominal wall reconstruction has been achieved in 92% of patients with complex abdominal defects.

Abdominal Muscles↗

Vascularized bone flaps versus nonvascularized bone grafts for mandibular reconstruction: an outcome analysis of primary bony union and endosseous implant success.

BACKGROUND: Functional restoration following resection or traumatic injury to the mandible depends on the reliability of the bony reconstruction to heal primarily and support endosseous implants. Although vascularized bone flaps (VBF) and nonvascularized bone grafts (NVBG) are both widely used to reconstruct the mandible, indications for each remain ill-defined. The purpose of this study was to compare bone graft/flap healing and success of implant placement in patients reconstructed with VBF versus NVBG. METHODS: Over the past 10 years, 75 consecutive mandibular reconstructions were performed (26 free bone grafts, 49 vascularized bone flaps). Etiology of the defect, history of irradiation, bone defect size, number of operations, graft/flap success, and dental implant success rates were determined and compared. Bone graft/flap success was defined as complete bony union. Implant success was defined as complete osseointegration. Mean follow-up was 3 years. RESULTS: Free flaps were used primarily for malignant disease (78%, 38/49). Bone grafts were used primarily for benign disease (88%, 23/26). History of prior irradiation: 11% (3/26) NVBG versus 45% (22/49) VBF. Length of bony defect (mean): 8.1 cm NVBG versus 9.4 cm VBF. Successful bony union, any size defect: 69% (18/26) NVBG versus 96% (47/49) VBF (p < .0005); lateral defects only: 75% (15/20) NVBG versus 100% (17/17) VBF (p < .05). Number of operations to achieve bony union (mean), any size defect: 2.3 NVBG versus 1.1 VBF (p < .001); lateral defects only: 1.9 NVBG versus 1.0 VBF (p < .005). Twenty-two patients (29%) had a total of 104 endosseous implants placed (NVBG: 8 patients, 33 implants; VBF: 14 patients, 71 implants). Immediate implants placed: 0/33 NVBG versus 54% (38/71) VBF. Overall implant success: 82% (27/33) NVBG versus 99% (70/71) VBF (p < .0001). Implant success in VBF patients with a history of RT: 100% (15/15). CONCLUSIONS: Despite the fact that patients reconstructed with VBFs were older, had larger defects, and were treated primarily for malignant disease and therefore had a higher incidence of irradiation to the affected mandible than in patients treated with NVBGs, the incidence of bony union was higher, requiring fewer operations to achieve union, and the implant success rate was significantly greater than for NVBG patients. Results were similar when considering lateral defects only. Based on these results, VBFs are indicated in most cases of mandibular reconstruction; NVBGs are effective for short bone defects (<5-6 cm), in nonirradiated tissue, and/or in patients determined to be too medically compromised to tolerate the additional operative time required for a free-flap reconstruction.

Adolescent↗

Donor-specific tolerance induction in composite tissue allografts.

BACKGROUND: Although prolonged composite tissue allograft (CTA) survival is achievable in animals using immunosuppressive drugs, long-term immunosuppression of CTAs in the clinical setting would be unacceptable for most patients. The purpose of this study was to develop a model for reliable CTA tolerance induction in the adult rat across a strongly antigenic MHC mismatch without the need for long-term immunosuppression. METHODS: Chimeras were prepared using rat strains with strong MHC incompatibility [WF (RT1Au) + ACI (RT1Aa) --> WF, n = 13]. Syngeneic (WF) and allogeneic (ACI) bone marrow (BM) was harvested and T-cell depleted. Following confirmation of T-cell depletion by flow cytometry, a mixture of T-cell depleted syngeneic and allogeneic BM was injected into the recipient animals (all recipients pretreated with low-dose irradiation, 500 to 700 cGy). In addition, the recipient animals received a single dose of ALS (10 mg) 5 days prior to bone marrow transplantation (BMT) and tacrolimus (1 mg/kg/day) from the day prior to BMT to 10 days postoperatively. Rat chimeras were characterized by flow cytometry at 3 and 12 months after BM reconstitution and following hindlimb transplantation. RESULTS: Peripheral blood lymphocyte chimerism (WF/ACI) remained stable >12 months after BM reconstitution in 10 of 13 animals. Multilineage chimerism of both lymphoid and myeloid lineages was present, suggesting that engraftment of the pluripotent rat stem cell had occurred. In animals with donor chimerism >60%, there was no sign of limb rejection for the duration of the study. All animals with chimerism <20% developed moderate signs of rejection clinically and histologically. Gross motor and sensory reinnervation (weight bearing, toe spread) occurred at >60 days in 6 of 9 rats. Postoperative flow cytometry studies demonstrated stable chimerism in all animals studied (n = 7). CONCLUSIONS: Stable mixed allogeneic chimerism can be achieved in a rat hindlimb model of composite tissue allotransplantation. Hindlimb allografts to mixed allogeneic chimeras exhibit prolonged, rejection-free survival. This represents the first reliable model demonstrating rejection-free CTA survival in an adult animal without the long-term use of immunosuppressive agents across a strongly antigenic MHC mismatch.

Animals↗

Flap selection as a determinant of success in pressure sore coverage.

OBJECTIVE: To establish a treatment algorithm for the long-term surgical management of pressure sores. DESIGN: Retrospective case series. SETTING: University-based teaching hospital. PATIENTS: From March 1979 to July 1995, 280 unselected pressure sore reconstructions (113 ischial, 94 sacral, and 73 trochanteric sores) were performed in 201 patients (130 men and 71 women; age range, 16-90 years; mean, 50 years). Of the patients, 90% had severe spinal cord injuries (paraplegia or quadriplegia). Forty-one percent of the wounds were chronic (present longer than 3 months). MAIN OUTCOME MEASURES: Length of stay, postoperative morbidity and mortality, and flap success (defined as a completely healed wound). RESULTS: Overall, 89% of the flaps healed primarily (ischium, 83% [94/113]; sacrum, 91% [86/94]; trochanter, 93% [68/73]). Three fourths of cases were treated in a single stage (debridement and reconstruction). The inferior gluteus maximus island flap (ischium) (94% [32/ 34]), the V-Y gluteus maximus advancement flap (sacrum) (97% [36/37]), and the tensor fascia lata flap (trochanter) (95% [42/44]) had the highest success rates. Flap success was not significantly affected by the size of the pressure sore or the number of previous flaps used. Postoperative hospital stays averaged 20 days. The overall complication rate was 28%, most commonly from a slight wound edge dehiscence. CONCLUSIONS: Flap selection and the appropriate short- and long-term sequence of flap use significantly improve success rates for pressure sore coverage. Reconstruction can be reliably performed in a single stage with a relatively short hospitalization.

Adolescent↗

Ischial pressure sore coverage: a rationale for flap selection.

The role of wound debridement and flap coverage in treating pressure sores is clearly established. However, criteria and supportive clinical data for specific flap selection and the sequence of flaps for coverage of the ischium remain ill-defined. From 1979-1995, 114 consecutive patients underwent flap coverage of 139 ischial pressure sores. Preoperative risk factors, prior flap history, defect size, flap success, complication rates, and the length of hospitalization were retrospectively evaluated and compared for 112 flaps in 87 patients. Flap success was defined as a completely healed wound. Average follow-up was 10 months (range: 1 month-9 years). Overall, 83% (93/112) of the flaps healed. In the majority of cases (75%, 84/112), wound debridement and flap reconstruction was achieved in a single stage. However, there were significant differences in the healing rates among the various flaps used. The inferior gluteus maximus island flap and the inferior gluteal thigh flap had the highest success rates, 94% (32/34) and 93% (25/27), respectively, while the V-Y hamstring flap and the tensor fascia lata flap had the poorest healing rates, 58% (7/12) and 50% (6/12), respectively. Flap success was not significantly affected by the age of the patient or the prior number of flaps used and preoperative risk factors were equally distributed across all types of flaps. The overall complication rate was 37% (41/112), most commonly from a slight wound edge dehiscence (n = 16) that healed with local wound care within one month postoperatively. Results of this study show that proper flap selection and the appropriate sequence of flap use significantly improve success rates for ischial pressure sore coverage in both the short- and long-term. Based upon flap reliability (successful healing rates), reusability, and the need to preserve as many future flap options as possible, a rationale for flap selection is presented which can be individualized to any patient.

Adolescent↗

The free fibula bone graft for salvaging failed mandibular reconstructions.

PURPOSE: The purpose of this study was to determine the efficacy of vascularized free fibula bone grafts for mandibular salvage reconstruction. PATIENTS AND METHODS: Seven patients had fibula grafts after failed attempts at mandibular reconstruction. The prior attempts involved 20 operative procedures. Four of the seven patients (57%) had a history of radiation to the affected mandible. Bony defects averaged 10.2 cm (range, 4.5 to 24 cm), and the associated soft tissue defects averaged 6 x 12 cm. Average follow-up was 16 months. Cosmetic (facial symmetry) and functional (speech quality, oral continence, deglutition, donor site morbidity, dental rehabilitation) results were evaluated by questionnaire and clinical examinations. RESULTS: Soft tissue coverage and mandibular restoration were successful in all patients, and flap survival was 100%. Five of the seven patients (70%) achieved good or excellent functional results, and five of seven (70%) achieved good or excellent esthetic results. Complications were minimal, and the average hospital stay was 14 days. CONCLUSIONS: When the initial attempt at mandibular reconstruction is unsuccessful, mandibular function and esthetics can be salvaged with reliable vascularized soft tissue and bone flaps. As long as appropriate flap options are considered and the patient is medically stable, successful mandibular reconstruction should be achievable despite the number or cause of prior failed attempts.

Adult↗

Lymphatic regeneration following microvascular limb replantation: a qualitative and quantitative animal study.

Lymphatic regeneration following unilateral hindlimb autotransplantation was studied in 14 Lewis rats using Technetium-99 radiolabeled sulfur colloid (TC-99) lymphoscintigraphy and compared to the lymphatic pattern exhibited in four unoperated control rats. Control animals demonstrate a reproducible flow of lymph along the deep lymphatic system from the foot, draining into the ipsilateral inguinal nodes, and then up to the para-aortic nodes. Following replantation, lymphatic outflow from the replanted limb begins to occur within 3 to 6 days, reaching normal lymphatic clearance within 12 days. However, the pattern of lymphatic flow is ill-defined, relying on multiple small channels of the superficial lymphatic system. In contrast to controls, at 3 hr post TC-99 injection, lymphatic drainage in replanted rats is via the inguinal and axillary nodal regions bilaterally. This abnormal pattern persisted in the replanted animals for the duration of this study, 160 days. It is evident that lymphatic regeneration in this animal model is associated with a rapid return to normal levels of lymphatic clearance via collateral channels within the subcutaneous tissue. The rapidity with which lymphatic drainage is restored, and its localization within the subcutaneous tissue, can explain why replanted tissues and microvascular free flaps seldom develop lymphedema. In addition, the rat hindlimb replantation model may prove useful for studies of the general mechanisms and specific factors responsible for lymphangiogenesis.

Animals↗

Fibular free flap reconstruction of the "true" lateral mandibular defect.

The purpose of this study was to determine the role of the fibular free flap in reconstructing lateral segmental defects of the mandible. Over the past 5 1/2 years, 17 consecutive patients underwent reconstruction of their lateral mandible with the fibular free flap. Patients included 12 men and 5 women, the mean age was 54 years (range, 29-76 years), and the mean length of the mandibular defect was 6.3 cm (range, 2.5-9 cm). The majority of patients with tumors (54%) were treated for recurrence and 92% received radiation to the operative field. The mean operative time to perform the microsurgery and bone plating was 4 hours. Postoperative morbidity occurred in 3 patients (18%) (plate fracture, malocclusion, orocutaneous fistula). Five patients (29%) required leg donor site skin grafting. Donor site morbidity included a minor cellulitis, a transient neuropraxia, and one case of leg swelling. None required additional surgery for donor complications. Thus far, 71% of the patients have received dental rehabilitation and 35% had osseointegrated implants placed in their bone flap. Eighty-two percent of the patients achieved both good or excellent aesthetic and functional results. Sixteen patients (94%) tolerate at least a soft diet and 65% are on a regular diet. Five patients developed tumor recurrence an average of 9 months postoperatively with a mean survival of 21 months. This study demonstrates that the fibular free flap is highly reliable for reconstructing the lateral mandible in a single stage, with low overall morbidity, and provides for excellent dental and speech rehabilitation. For most patients, the fibular free flap should be considered for lateral mandibular reconstruction even in those patients with a limited life expectancy.

Adult↗

Reconstruction of complex midfacial defects.

Modern treatment of complex midfacial defects has evolved over the past 5 years, primarily with the advent of reliable vascularized bone flaps and osseointegrated implants. To determine the effectiveness of these advances, 26 consecutive patients with complex midfacial defects treated from 1991 through 1995 with immediate muscle-flap coverage were evaluated. The etiology of the defect included neoplasm (n = 23) and trauma (n = 3). Seventy-eight percent of the patients received adjuvant radiation therapy. Follow-up ranged from 3 months to 4 years, with a mean of 18 months. Twenty-three patients (88 percent) were reconstructed with a single major procedure. All patients had free-flap reconstruction, and 100 percent of the flaps survived. Late tumor recurrence was seen in 5 of 23 patients (22 percent) and was detected promptly. Aesthetic and functional results were rated good or excellent in 77 and 88 percent of the patients, respectively, as determined by patient questionnaires and physical examinations. Fourteen of 18 patients (78 percent) undergoing partial or complete alveolar ridge resection received dental rehabilitation, 43 percent of whom received osseointegrated implants into either a bone flap or remaining native bone. Osseointegrated implants were inset during the initial reconstruction 50 percent of the time. A treatment algorithm for free-flap selection based on the size of the defect and the bony requirement for reconstruction is presented. Bony restoration is only required in those areas where osseointegrated implants need to be placed. In such cases, the fibula osteocutaneous free flap is the flap of choice. Otherwise, soft-tissue flaps are selected based on wound size. Immediate free-flap coverage provides effective, single-stage treatment, both aesthetically and functionally, for complex midfacial defects.

Adolescent↗

Microsurgical reconstruction of the midface.

OBJECTIVE: To establish a treatment algorithm for reconstructing complex midfacial defects. DESIGN: Retrospective case series. SETTING: University-based teaching hospital. PATIENTS: Thirty-one consecutive patients were treated from 1991 through 1995. The 18 males and 13 females were aged 15 to 90 years (mean age, 58 years). The cause of the defect included neoplasm (n = 27) and trauma (n = 4). Reconstruction consisted of 1 of 4 free flaps: rectus abdominis, radial forearm, fibula, or latissimus dorsi. Aesthetic and functional results were determined by patient questionnaires and physical examinations. MAIN OUTCOME MEASURES: Length of stay, postoperative morbidity and mortality, degree of aesthetic and functional restoration, and detection of tumor recurrence. RESULTS: Twenty-seven (87%) of the 31 patients underwent reconstruction with a single major procedure. All of the flaps survived. Postoperative hospital stays averaged 14 days. Late tumor recurrence occurred in 7 (23%) of the 31 patients and was promptly detected. Aesthetic and functional results were rated good or excellent in 77% (24/31) and 87% (27/31) of patients, respectively. Of the 20 patients who underwent alveolar ridge resection, 16 (80%) received dental rehabilitation, 44% of whom received osseointegrated implants into either a bone flap or remaining native bone. Osseointegrated implants were inset during the initial reconstruction 57% (4/7 patients) of the time. CONCLUSIONS: For complex midfacial defects, free-flap transfer can be performed with a high degree of success, restoring both appearance and function in most patients. The only instance in which bone is necessary to reconstruct the midface involves those areas in which osseointegrated implants are needed, ie, alveolar ridge (dental implant) and/or orbit (ocular prosthesis). In such cases, the fibula osteocutaneous free flap is the flap of choice. Otherwise, soft-tissue flaps are selected based on wound size.

Adolescent↗

Reconstruction of a complex midfacial defect with the folded fibular free flap and osseointegrated implants.

Refinements in microsurgical techniques, plate fixation, and osseointegration have changed the conceptual approach to midface reconstruction. Free tissue transfer has emerged as the ideal method of reconstructing complex midfacial defects. Single-stage bony restoration of the palate and orbital rim using the folded fibular osteocutaneous free flap is described. The fibular free flap is our first choice for reconstructing complex midfacial defects. The thin, soft, pliable tissue is ideal for intraoral and palatal reconstructions. The bone can be tailored precisely to fit any desired shape, and forms a sturdy support for both orbital and dental prostheses. With a single flap, rapid and reliable restoration of midfacial appearance, orbital support, and palatal function can be achieved.

Adult↗

Acute compartment syndrome of the thigh: case report.

Compartment syndrome of the thigh is a recognized, yet uncommon, condition characterized by excessive thigh pain following trauma, especially if accompanied by decreasing neurological function. A case is presented in a patient with a subtrochanteric fracture of the femur due to a gunshot wound. Surgical decompression corrected the problem.

Adult↗

A radiographic and histological analysis of 17 retrieved ultrahigh-molecular-weight polyethylene porous-coated femoral stems.

Radiographic and histological and evaluation for failure of 17 retrieved implants was performed. The implants consisted of a titanium stem with a 3-mm ultrahigh-molecular-weight polyethylene coating and an outer 1.5-mm ultrahigh-molecular-weight polyethylene fiber layer. Particular attention was paid to osteolysis, subsidence, debris, and foreign body reaction. Radiographic analysis showed subsidence (14 of 17), osteolytic lesions (9 of 14), and unique posterior medial exostoses (8 of 14). Histological analysis showed no significant evidence of acrylic bone cement either as debris or reactive tissue. There was an intense foreign body reaction directly related to the amount and size of polyethylene debris.

Adult↗