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Biomedical subjects

W G Rodkey

Publications and source records attributed to W G Rodkey.

At least 19 recordsLinked to original sources

Microfracture: surgical technique and rehabilitation to treat chondral defects.

Full-thickness articular cartilage defects rarely heal spontaneously. Some patients may not have clinically significant problems from chondral defects, but most eventually have degenerative changes. Techniques to treat chondral defects include abrasion, drilling, autografts, allografts, and cell transplantation. The senior author (JRS) developed the microfracture technique to enhance chondral resurfacing by providing a suitable environment for new tissue formation and taking advantage of the body's own healing potential. Microfracture has been done in more than 1800 patients. Specially designed awls are used to make multiple perforations, or microfractures, into the subchondral bone plate. Perforations are made as close together as possible, but not so close that one breaks into another. They usually are approximately 3 to 4 mm apart. The integrity of the subchondral bone plate must be maintained. The released marrow elements (including mesenchymal stem cells, growth factors, and other healing proteins) form a surgically induced super clot that provides an enriched environment for new tissue formation. The rehabilitation program is crucial to optimize the results of the surgery. It promotes the ideal physical environment for the marrow mesenchymal stem cells to differentiate into articular cartilagelike cells, ultimately leading to development of a durable repair cartilage that fills the original defect.

Cartilage, Articular↗

Basic biology of the meniscus and response to injury.

This brief description of the basic biology of the meniscus helps to demonstrate that the menisci are an integral part of the complex biomechanics of the knee. Without the menisci, the normal knee joint function is severely diminished. Lack of the menisci typically leads to progressive degenerative joint disease of the knees. Efforts must be continued to find better methods and techniques to manage meniscus injuries. Improved therapy will help minimize the late instability of the joint, decrease pain associated with loss of the meniscus, minimize or prevent degenerative joint changes, and obviate the need for multiple surgical procedures. Specific targets should include improved methods of meniscectomy, new and better techniques of repair for meniscus tears, methods to enhance the cellular response for healing of meniscus tissue, and, finally, new ways to regenerate lost or damaged tissue.

Arthroscopy↗

[The microfracture technic in the management of complete cartilage defects in the knee joint].

Full thickness defects of the articular cartilage rarely heal spontaneously. While some patients do not develop clinically significant problems from chondral defects, most eventually develop degenerative changes associated with the cartilage damage over time. Techniques to treat chondral defects include abrasion, drilling, tissue autografts, allografts, and cell transplantation. The senior author has developed a procedure referred to as the "microfracture." This technique enhances chondral resurfacing by providing a suitable environment for tissue regeneration and by taking advantage of the body's own healing potential. This technique has now been used in more than 1400 patients. Specially designed awls are used to make multiple perforations, or "microfractures", into the subchondral bone plate. The perforations are made as close together as necessary, but not so close that one breaks into another. Consequently, the microfracture holes are approximately three to four millimeters apart (or 3 to 4 holes per square centimeter). Importantly, the integrity of the subchondral bone plate is maintained. The released marrow elements form a "super clot" which provides an enriched environment for tissue regeneration. Follow up with long term results of more than 8 years have been positive and very encouraging.

Bone Regeneration↗

A clinical study of collagen meniscus implants to restore the injured meniscus.

The meniscus performs critical functions within the knee, and its loss frequently leads to osteoarthritis and irreversible joint damage. Because prosthetic replacement of the meniscus has proven ineffective, the authors used tissue engineering techniques to develop a resorbable collagen scaffold (collagen meniscus implant) that supports ingrowth of new tissue and eventual regeneration of the lost meniscus. Eight patients underwent arthroscopic placement the collagen meniscus implant to reconstruct and restore the irreparably damaged medial meniscus of one knee. Seven patients had one or more prior meniscectomies, and one patient had an acute meniscus injury. Patients were observed with frequent clinical, serologic, radiographic, and magnetic resonance imaging examinations for at least 24 months (range, 24-32 months). All patients underwent relook arthroscopy and biopsy of the implant regenerated tissue at either 6 or 12 months after implantation. All patients improved clinically from preoperatively to 1 and 2 years postoperatively based on pain, Lysholm scores, Tegner activity scale, and self assessment. Relook arthroscopy revealed tissue regeneration in all patients with apparent preservation of the joint surfaces based on visual observations. Histologic analysis confirmed new fibrocartilage matrix formation. Radiographs confirmed no progression of degenerative joint disease. The collagen meniscus implant is implantable, biocompatible, resorbable, and supports new tissue regeneration as it is resorbed. This tissue seems to function similar to meniscus tissue by protecting the chondral surfaces.

Arthroscopy↗

Role of MR imaging in sports medicine research. Basic science and clinical research studies.

The advent and advancement of MR imaging have provided an entire new dimension for medical imaging. MR imaging has been especially useful because of its capacity to image nonmineralized tissues with a very high degree of resolution. Although modalities such as ultrasound and scintigraphy have proven useful for specific purposes, it is MR imaging that has the most utility and capabilities, especially in the area of sports-induced injuries. The technology associated with MR imaging has expanded greatly, and it continues to evolve at a rapid pace. The result has been an ever-increasing diagnostic capability that has become more economic with time. As described previously, MR imaging is gaining importance in the area of comparative medicine for animal athletes as well. It is also interesting to note that MR imaging now has a greater potential for monitoring physiological and biochemical changes as well as anatomic ones. Some newer MR units actually include physiologic data acquisition components. Consequently, new bioassays and nondestructive tissue tests can be performed to further understand the molecular biology and ongoing cellular processes in any given condition. Coupled with MR spectroscopy, the enhanced MR techniques should continue to contribute to the overall information that will be integrated into the training and rehabilitation of patients with sports-induced inflammation and injuries. The authors support and encourage ongoing efforts in the area of MR imaging research, both basic science and clinical studies.

Animals↗

Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data.

A collagen scaffold was designed for use as a template for the regeneration of meniscal cartilage and was tested in ten patients in an initial, Food and Drug Administration-approved, clinical feasibility trial. The goal of the study was to evaluate the implantability and safety of the scaffold as well as its ability to support tissue ingrowth. The study was based on the findings of in vitro and in vivo investigations in dogs that had demonstrated cellular ingrowth and tissue regeneration through the scaffold. Nine patients remained in the study for at least thirty-six months, and one patient voluntarily withdrew after three months for personal reasons. The collagen scaffold was found to be implantable and to be safe over the three-year period. Histologically, it supported regeneration of tissue in meniscal defects of various sizes. No adverse immunological reactions were noted on sequential serological testing. On second-look arthroscopy, performed either three or six months after implantation, gross and histological evaluation revealed newly formed tissue replacing the implant as it was resorbed. At thirty-six months, the nine patients reported a decrease in the symptoms. According to a scale that assigned 1 point for strenuous activity and 5 points for an inability to perform sports activity, the average score was 1.5 points before the injury, 3.0 points after the injury and before the operation, and 2.4 points at six months postoperatively, 2.2 points at twelve months, 2.0 points at twenty-four months, and 1.9 points at thirty-six months. According to a scale that assigned 0 points for no pain and 3 points for severe pain, the average pain score was 2.2 points preoperatively and 0.6 point thirty-six months postoperatively. One patient, who had had a repair of a bucket-handle tear of the medial meniscus and augmentation with the collagen scaffold, had retearing of the cartilage nineteen months after implantation. Another patient had debridement because of an irregular area of regeneration at the scaffold-meniscus interface twenty-one months after implantation. Magnetic resonance imaging scans demonstrated progressive maturation of the signal within the regenerated meniscus at three, six, twelve, and thirty-six months. These findings suggest that regeneration of meniscal cartilage through a collagen scaffold is possible. Additional studies are needed to determine long-term efficacy.

Adult↗

Autogenous replacement of the meniscus cartilage: analysis of results and mechanisms of failure.

Autogenous replantation of meniscal cartilage (resection of 80% of the meniscus cartilage followed by immediate replantation) was performed in 14 dogs as a control arm of a meniscal replacement study. The purpose was to assess the ability of the excised tissue to heal to the intact rim and function as a meniscus cartilage. This procedure is an idealized model of allografting meniscus cartilage in that the tissue is fresh, autogenous, and perfectly sized. If this procedure did not succeed, it seemed likely to the authors that allografting meniscal cartilage would have diminished chances for success. Evaluation of these replant failures led us to speculate that the causes and mechanisms might include slow or incomplete revascularization, inadequate mechanical fixation or stabilization, and, perhaps, some type of rejection phenomenon not examined or confirmed in the present study. We believe these mechanisms will be particularly deleterious for allografted meniscal cartilages and recommend further extensive evaluation of meniscal allografts before wide clinical use.

Animals↗

Role of primary anterior cruciate ligament repair with or without augmentation.

Primary ACL repair with or without extra-articular augmentation can be functionally and statically successful based on our experience in high-performance athletes. Proper surgical technique, appropriate rehabilitation, and excellent quality of the tissue being repaired are required to achieve these results. Several notable improvements in diagnostic imaging, physical examination, surgical technique, and rehabilitation protocol have led to excellent results. The notchplasty, multiple loop suture technique, and improved meniscal repair are key factors. Moreover, we believe that one of the prime enhancements is to provide the highly stable extra-articular lateral capsular ligament reconstruction described previously. Laboratory findings have shown that this procedure provides excellent support against anterior subluxation immediately after surgery. It appears that release of the iliotibial band tissue proximally prevents stretching and failure of this extra-articular procedure. Rehabilitation unquestionably is a critical factor in the success of this surgical procedure. Immediate motion and appropriate biomechanical stresses on the repaired ligament have proved compatible with good functional and objective results. Even though intra-articular reconstruction of the torn ACL continues to be considered the gold standard, we remain convinced that primary repair of the ACL with appropriate extra-articular augmentation should not be ruled out in many cases. This procedure clearly is a viable, successful, and acceptable alternative to intra-articular reconstruction in selected cases.

Anterior Cruciate Ligament↗

Alpine skiing and the mature athlete.

Alpine skiing is a popular sport enjoyed by millions of Americans annually. As the average age of the world population increases, so does the average age of the skier. The ever-increasing older group of skiers adds a new dimension to both the prevention and treatment of ski injuries. Several injuries, if not unique to the older skier, are more common in this group, and familiarity with the causes, treatments, risks, and avoidance of these injuries is essential for proper treatment. It is possible that with proper education, prevention, and physical training, the incidence of these injuries can be decreased to the level of the general population, and skiing will not be more hazardous to the older athlete.

Aged↗

Hypertonic saline/dextran improves renal function after hemorrhage in conscious swine.

This study was performed to determine whether resuscitation with a single bolus of 7.5% NaCl/6% Dextran 70 (hypertonic saline/Dextran, HSD) could restore renal function following hemorrhage. Chronically instrumented, conscious pigs were hemorrhaged 28 ml/kg. This level of hemorrhage reduced mean arterial pressure (MAP) and cardiac output (CO) to nearly half, renal blood flow (RBF) to approximately 25%, and glomerular filtration rate (GFR) and urine flow (V) to less than 10% of their initial values. A single, 4 ml/kg bolus injection of HSD increased MAP and RBF to approximately 80% of baseline values and restored CO and GFR to levels which were significantly different from control values. These improvements were sustained for 2 h with no further treatment. Urine flow transiently increased although not to pre-hemorrhage values, and then subsided. Plasma osmolality increased from 275 to 282 mOsm/kg H2O, and plasma sodium increased from 141 to 149 mEq/l. Recovery following administration of an equal volume of normal saline was significantly less for all variables. Euvolemic animals showed no response in MAP, CO, RBF, or GFR when treated with HSD although V, osmotic and sodium excretion increased. These results demonstrate that resuscitation with HSD following hemorrhage not only restores MAP and CO, but maintains renal function as well.

Acute Kidney Injury↗

Renal responses to graded hemorrhage in conscious pig.

We developed a conscious pig model with a chronically instrumented kidney to measure renal blood flow (RBF), glomerular filtration rate (GFR), and excretory functions during hemorrhage. Seven to 10 days before experimentation, pigs were splenectomized, arterial and venous catheters were implanted, an ultrasonic flow probe was placed on the renal artery, and a pyelostomy was performed for nonocclusively placing a ureteral catheter. Measurements were taken before hemorrhage, and at hemorrhage volumes of 7, 14, 21, and 28 ml/kg (equivalent to 10.5, 21, 31, and 42% of the estimated blood volume), or at corresponding time points for controls. RBF was decreased by 30% when 21% of the blood (14 mg/kg) was removed, before arterial pressure, GFR, or urine flow or excretion was changed. At volumes of hemorrhage greater than 14 ml/kg, there were progressive decreases in RBF, GFR, urine flow rate, osmotic and electrolyte excretion, and arterial pressure. Thus pigs, like humans, respond to hypovolemia with an early redistribution of blood flow away from the kidney.

Animals↗

Future directions. Collagen-based prostheses for meniscal regeneration.

Prosthetic meniscal replacement offers the ability to stabilize the meniscectomized knee and provide prophylaxis against early degenerative arthritis. Since prosthetic meniscal replacement may be performed in the setting of normal articular cartilage, a prosthesis will be required to match the exact joint configuration, induce the same lubricity, produce the same coefficient of friction, and absorb and dampen the same joint forces (without incurring significant creep or abrasion) as does the normal meniscus. This feat is currently beyond the capabilities of artificial materials alone. Alternatively, collagen-based prostheses acting as resorbable regeneration templates offer the possibility of inducing regrowth of new menisci. This paper presents a summary of hypotheses, considerations, and laboratory evidence for the use of collagen-based, resorbable matrices as regeneration templates.

Animals↗

Laser angioplasty: an atherosclerotic swine model.

Rapid production of occlusive, atherosclerotic iliac artery lesions was achieved in 25 of 27 (93%) Yucatan miniature swine, using a combination of high cholesterol diet and mechanical endothelial denudation. Animals were fed a diet with 2% of their calories as raw cholesterol 2 weeks prior to balloon denudation of iliac arteries, which resulted in atherosclerotic lesions within 8 weeks. Early after denudation we have demonstrated total occlusion of arteries by fibrin thrombi, which in time organize and ultimately result in fibrotic occlusive disease. The arterial walls and intima show varying degrees of foam cell infiltration with destruction of the internal elastic lamina and calcification. Totally occluded lesions show fibrointimal proliferation, fibrosis, and multiluminal channels, which are probably secondary to organized thrombus. Our model of occlusive iliac artery disease involving vessels of 1 to 3 mm in diameter allows the development of catheter systems suitable for use in human peripheral and coronary arteries. This model is useful for the study of angioplasty, whether mechanical, balloon, or laser-mediated.

Angioplasty, Balloon↗

Splenic red cell sequestration and blood volume measurements in conscious pigs.

When estimated by the dilution of 51Cr-labeled red blood cells under nearly basal conditions, immature splenectomized pigs (n = 20) had a circulating red cell volume of 17.8 +/- 1.64 (SD) ml/kg. At an assumed body-to-large vessel hematocrit (BH:LH) ratio of 0.9, plasma volume was 49.6 +/- 3.12 ml/kg and blood volume 67.3 +/- 3.67 ml/kg. Sham-operated pigs (n = 20) had a circulating red cell volume of 16.2 +/- 1.39 ml/kg, a plasma volume of 51.1 +/- 3.42 ml/kg, and blood volume of 67.2 +/- 4.12 ml/kg. Kinetic analysis of early 51Cr loss from the circulating blood of the sham-operated pigs indicated a splenic red cell sequestration of 4.5 +/- 0.89 ml/kg and a t1/2 of 9.76 +/- 1.93 min for splenic red cell turnover. Epinephrine injection (n = 6) and physical restraint (n = 8) caused rapid mobilization of splenic red blood cells in sham-operated pigs. Volume estimates in splenectomized pigs (n = 7) based on simultaneous dilutions of 51Cr-labeled red blood cells and 125I-labeled bovine albumin gave circulating red cell, plasma, and blood volumes of 18.4 +/- 2.46, 60.7 +/- 4.01, and 79.0 +/- 3.51 ml/kg, respectively, and a BH:LH ratio of 0.756 +/- 0.029. The latter value may have reflected an overestimation of plasma volume by the 125I-labeled albumin procedure.

Animals↗

Philosophy and rationale for the management of anterior cruciate injuries and the resultant deficiencies.

Deficiency of the anterior cruciate ligament (ACL) results in the loss of the fine tuning of the knee joint. Either acute loss or chronic insufficiency of ACL function results in instability, tricking, and giving way, and subsequently the fluid gliding mechanics of the knee joint are significantly altered. Regardless of the length of time from injury to evaluation, it is imperative that a correct and complete diagnosis be made before a treatment program is selected. Functional stability, the goal, can be accomplished only by limiting clinical laxity through a combination of appropriate surgery and functional rehabilitation.

Acute Disease↗

Pharmacokinetics of hemoglobin infusion.

Although research with acellular Hb solutions has been conducted for many years, published data concerning the pharmacokinetics of Hb are quite variable. Preliminary research in this Division has attempted to establish an adequate pharmacokinetic model for SFH and for a modified Hb product. Three dose levels of SFH (55 mg/kg, 111 mg/kg, and 1400 mg/kg were given by rapid (less than 10 min.) intravenous injection to different groups of dogs. Serial blood samples were obtained from indwelling intravenous catheters and plasma Hb levels were measured. Analysis of the plasma SFH concentration-time data showed a first order decline at all three dose levels with no significant (p less than 0.05) difference in elimination rate constants. A significant difference in the volume of distribution at each dose was seen which suggested greater tissue deposition of Hb at higher doses. Consideration of the normalized AUC suggested a non-linear elimination process at high doses. This process appears to be consistent with known Hb elimination mechanisms. A single dose of PPHb was also studied. Following a dose of 650 mg/kg, the plasma Hb levels decline was characterized by a single compartment model with Michaelis-Menten elimination. The model parameters calculated are preliminary and further work is needed to evaluate the model.

Animals↗

Progressive ultrastructural changes after peripheral nerve transection and repair.

Six rhesus monkeys (Macaca mulatta) underwent sharp transection and repair of the intrinsic motor fascicles of both ulnar nerves in order to determine the sequential events during reinnervation of the distal stamp. Light and electron microscopic sections were made at 2.0 mm increments distal to the neurorrhaphy at weekly intervals in separate monkeys. Neurite sprouts could be identified distal to the neurorrhaphy by 1 week and were clearly evident 40 mm distal by 3 weeks. Although some old endoneurial tubules persisted, they were less often used as conduits or scaffolds for the regenerating neurites than previously described. Most new fibers, whether myelinated or unmyelinated, passed down new endoneurial tubules, thus precluding perfect end-organ specificity because the regenerating neurites seldom utilized old endoneurial tubules. The clinical implication suggested by this study is that the ideal situation is the immediate repair of transected nerves. This allows neurite sprouts to cross a neurorrhaphy rapidly and reinnervate end organs.

Animals↗