Xenotransplantation of neonatal porcine liver cells.

Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

Preservation of murine embryos in a state of dormancy at 4 degreesC.

With the aim of improving preservation of blood products and organs for transplantation, we designed solutions to induce a state of dormancy in cells and tissues at 4 degreesC. The solutions were devoid of combinations of ions (e.g., K+, Rb+, Cs+, and NH+4 with HCO-3, H2PO-4, and Cl-) that are believed to break down low-density water in the entrance compartments of ion channels, resulting in cyclical open states (normal water) and closed states (low-density water). The total osmolality was always 0.29-0.3 osmol/kgH2O, made up of combinations of a di- or trisaccharide, a compatible solute, sodium sulfate, citrate, or chloride, and 1.75 mM CaCl2. The end point was the ability of murine embryos to progress to hatching in culture after preservation in such a solution at 4 degreesC. Embryos hatched after 5 or 6 days in some preservative solutions compared with 1-3 days in most saline solutions; survival was improved by pretreatment with sodium butyrate.

Segmental vascular changes in the femoral head in children and adults.

The segmental nature of the avascular involvement of the femoral head in both children and adults is similar. Avascular necrosis may be wrongly interpreted from roentgenograms in infancy, irregular ossification may be due to altered stress on the femoral head. The segment involved in Legg-Perthes' disease is superior and lateral to the fovea in an area supplied by a branch of the lateral epiphyseal artery. Secondary changes occur due to the separation of the dead segment from the living bone. Theron demonstrated the vascular interruption with micro-injection techniques in both child and adult. Finite analysis of the femoral head revealed the distortion of the computer model at the site of the branches of the lateral epiphyseal artery. Trauma with vascular interruption within the femoral head appears to explain the avascular segment.

A comparison of the posterolateral and anterolateral approaches to total hip arthroplasty.

A comparative statistical analysis was performed weighing the relative merits of two surgical approaches for total hip arthroplasty--the Watson-Jones anterolateral approach and the gluteus maximus splitting posterolateral approach. Intraoperative and clinical records were evaluated for 175 patients undergoing total hip arthroplasty between 1975 and 1979--100 by a posterolateral approach and 75 by an anterolateral approach. Minimum follow-up period was two years. Mean operative times for the posterolateral and anterolateral approaches were 62 minutes and 140 minutes, respectively. The posterolateral group had a mean blood loss of 433 ml, with 35% requiring an average transfusion of 2.5 units. The anterolateral group had a mean blood loss of 767 ml, with 78% requiring an average transfusion of 2.5 units. The average lengths of hospitalization for posterolateral and anterolateral groups were 13 and 15 days, respectively. The time to independent cane ambulation was significantly less in the posterolateral group. The rate of post-operative complications was similar in each group. However, in the posterolateral group there were four dislocations, three loosened femoral components, one deep-wound infection, and one pulmonary embolus, while the anterolateral group suffered one dislocation, no prosthesis loosening, no deep-wound infections, and three pulmonary emboli. Although the posterolateral approach was associated with a lower perioperative morbidity than the anterolateral approach, the latter exhibited fewer dislocations and loosened acetabular components.

Elevation of the insertion of the patellar ligament for patellofemoral pain.

In an effort to evaluate the use of a transverse incision and a relatively small elevation (1.25 centimeters) of the tendinous insertion of the patellar ligament into the tibial tubercle, 184 patients were treated with a modified procedure using the Maquet principle. The indications for the procedure were patellofemoral pain and loss of active function. The patients were placed in five groups based on the cause of their symptoms: chondromalacia, patellofemoral arthritis, patellar dislocation, previous trauma, and previous patellectomy. The results were evaluated on the basis of whether or not primary wound-healing was satisfactory and whether or not the patient resumed the ability to ascend stairs and could engage in previously lost athletic function, Eighty-five per cent of the patients achieved these goals of treatment. The disadvantages of the procedure appeared to be the slow return of full function (averaging six months), prominence of the area of the tibial tubercle, and persistence of crepitus on patellofemoral motion.

A non-linear finite element analysis of some early collapse processes in femoral head osteonecrosis.

Some aspects of the early collapse biomechanics of the segmentally necrotic adult human femoral head were studied, using a small-deformation plane strain, elasto-plastic finite element model. The computational procedure used was based upon the initial stress technique, and permitted study of stress and strain fields and of the progression of failure regions as a function of incrementally applied joint loads. The results consistently demonstrated both subchondral and deep cancellous failure patterns similar to those seen clinically. There was a clear distinction, however, between these two failure regimes, dependent primarily upon the relative strength deficits input for the subchondral versus the deep cancellous regions. Usually, the failure zone was appreciable only at significantly supra-physiological loads, reflecting the likely importance of fatigue events in the clinical collapse process. Although subchondral failure was always limited to the entire base region of the infarction wedge, the zones of deep failure varied considerably with changes in lesion geometry, usually being concentrated within the infarct near the underlying necrotic/viable interface.

Mechanical characteristics of bone in femoral capital aseptic necrosis.

Uniaxial compression loading of small cube-shaped samples in an Instron machine was used to study material property deficits of middle- and late-stage necrotic cancellous bone taken from adult human femoral heads. Although the experimental data should not be extrapolated to phenomena of viable trabecular response in a functioning osteonecrotic hip, they provide insight into the salient passive mechanical response characteristics of the pathologic tissue. Individual differences in the revascularization and/or collapse patterns occurring within femoral heads lead to substantial variability in the strength and stiffness of test samples taken from the involved regions. As an overall average, however, samples extracted from major infarct regions exhibit substantially reduced (52%) yield strength, severely reduced (72%) elastic modulus, and modestly increased (29%) strain-to-failure, relative to samples from normal femoral heads. However, statistically significant changes are not observed in the Poisson ratio, the post-yield modulus, or in the incidence of pre-yield load/deformation discontinuities.

Load transmission through the proximal femur of the growing child: a finite element analysis.

Growth-related variations in the distribution of mechanical stress in the normal juvenile proximal femur are explored using a computer-based finite element stress analysis technique. Input data for the model are obtained from serial patient roentgenograms and from laboratory compression tests of fresh autopsy material. The results for the limiting case of epiphyseal closure (18-year-old male) are in substantive agreement with previous experimental and mathematical studies of the adult proximal femur. The computational results for the juvenile hip show that in spite of the complex morphological alterations occurring during growth, the basic mechanisms of load transmission at first ambulation are still operational at skeletal maturity. Foremost among these are the distally-concentrated weight bearing compressive stresses in the primary trabeculation system, the abductor-induced tensile stresses in the greater trochanter, and the large longitudinal stresses within the proximal femoral cortices. As growth advances, however, the importance of transverse compressive stresses in the proximal lateral metaphysis progressively diminishes, while shearing stresses in the plane of the epiphyseal plate increase markedly. These two major growth-related changes results largely from decreases in the neck-shaft angle, and if excessive, may be implicated in development coxa vara or slipped capital femoral epiphysis.

Relief of patellofemoral contact stress by anterior displacement of the tibial tubercle.

Elevation of the patellar tendon by means of displacement of the tibial tubercle has been advocated by Maquet, Ficat and Hungerford, and Murray as an alternative to patellectomy for the treatment of patellofemoral arthralgias. Although tubercle elevation certainly reduces the over-all patellofemoral contact force, its effects on the complex local patterns of contact stress are of more direct significance. In a laboratory series using fresh amputation material, arrays of six miniature contact stress sensors were embedded in the retropatellar cartilage of knees subjected to isometric quadriceps-extension forces. The experimental data revealed that elevation of the patellar tendon generally afforded relief of local contact stress regardless of the joint configuration (zero degrees, 45 degrees, or 90 degrees of flexion), but that its effects were most pronounced at 90 degrees of flexion. Progressive increase in the tendon elevation caused progressive reduction in the contact stress. Most of the contact stress relief was achieved, however, with the first one-half inch of tendon elevation; further elevations to one and one and one-half inches were only marginally useful. In view of the increased superior patellar pole contact associated with distal pole flotation, the results indicate that under most circumstances the optimum amount of elevation of the tibial tubercle is about one-half inch.

The development of a computational stress analysis of the femoral head. Mapping tensile, compressive, and shear stress for the varus and valgus positions.

Using a computer-based, two-dimensional finite-element analysis which has wide application to problems involving the hip joint, alterations in the distribution of stress in the femoral head consequent to varus and valgus osteotomy were studied. The mathematical model used in this analysis incorporated experimentally measured spatial variations in the stiffness of the bone of the femoral head and neck. These variations led to patterns of load transmission that were strikingly different from those in a homogeneous material. Because of their lower stiffness, the central region of the head and the medullary region of the neck make very little contribution to weight-bearing, regardless of the orientation of the femoral head. In the neutral configuration (normal neck-shaft angle), the lateral cortex of the neck is in slight tension, while the medial cortex is under strong compression and provides the support for the over-all load on the joint. With increasing valgus angulation, the bending component of the joint load disappears progressively, and when the valgus angulation is 30 degrees in excess of normal essentially equal compressive stresses prevail in both cortices. Varus osteotomy exaggerates the bending component relative to the compressive component of the load. The computed stress patterns in the femoral head and neck for the normal neck-shaft angle show elevations of shear stress where the lateral epiphyseal artery enters and branches within the femoral head. This finding may be significant since this region is the area at risk of infarction in both Legg-Perthes disease in children and idiopathic aseptic necrosis in adults. Since a 30-degree varus angulation induces tensile stresses in the lateral cortex of the neck that are increased fourfold above those for the neutral configuration, it is postulated that force transmitted through the femur when the hip is in abduction could produce shear fractures of the bone in the region of the central branch of the lateral epiphyseal artery and thus occlude this vessel and initiate aseptic necrosis of the femoral head.

Congenital vertical talus: treatment by open reduction and navicular excision.

Twelve patients with sixteen feet showing true congenital vertical talus were treated at Children's Hospital of Pittsburgh by excision of the navicular as an adjunct to open reduction. When these children were evaluated two to fifteen years after naviculectomy, all were asymptomatic and fully active. Except for one Achilles-tendon lengthening (three months after naviculectomy), none had required further surgical procedures. Fifteen feet were examined in detail. Assessed on an anatomical basis, three of the feet were excellent; seven, good; four, fair; and one, poor. The best results were obtained in the patients who were eighteen months old or younger at the time of operation.

Primary recognition and treatment of congenital dislocation of the hip.

The pathology associated with congenital dislocation of the hip has been reviewed. The pathophysiology as it affects the development of the hip under treatment makes a strong case for the avoidance of the "frog leg" position with fixed flexion and abduction of the hips in the plaster cast. It is apparent that tightness of the iliopsoas muscle and the underlying capsule makes that flexed abduction position necessary to hold the hip in position. The "frog leg" position is seriously implicated in the development of aseptic necrosis, not only of the dislocated hip but of the normal hip as well. The results seen in patients with surgical division of the iliopsoas tendon and capsular contracture, followed by leg immobilization in a functional position of extension at the hip accompanied by slight abduction and internal rotation, indicate the virtual elimination of the necessity for secondary reconstruction procedures on the hip at a later date. This appears to be the more conservative approach to treatment in children under age two. A period of one to three months in a splint that flexes and abducts the leg but permits changing positons may be tried before the obstruction is relieved. For children with lax capsule and iliopsoas, reduction may be possible by this route. For most the hip will be pressed in slightly improving the x-ray picture--but with the obstruction still before the femoral head. The seating of the femoral head must be exact. If it is not, imperfection in the development of the hip arises and may lead to later malfunction. Obstructions to perfect seating of the femoral head in the acetabulum must be overcome.