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Biomedical subjects

G A Murrell

Publications and source records attributed to G A Murrell.

At least 37 records · Page 2Linked to original sources
PubMed2000

The protective effects of meniscal transplantation on cartilage. An experimental study in sheep.

BACKGROUND: Meniscal loss may result in arthritis. The aim of this study was to establish a simple operative method for meniscal transplantation in a large-animal model and to determine whether meniscal transplantation provides protection of the articular surfaces, whether meniscal allografts have the same protective effect as meniscal autogenous grafts, and whether there is any rejection phenomenon associated with meniscal allografts. METHODS: Twenty-eight sheep were divided into four study groups, which were treated with (1) a sham operation (four sheep), (2) a meniscectomy (eight sheep), (3) a meniscal autogenous graft (eight sheep), or (4) a meniscal allograft (eight sheep). The meniscal transplant was secured with three suture anchors to the tibia. At four months after the operation, macroscopic and microscopic evaluations of the articular cartilage and the menisci of the sheep knees were performed in a blinded fashion. RESULTS: The group treated with the sham operation had no cartilage damage and had normal meniscal tissue. The meniscectomies resulted in significant macroscopic and microscopic damage to the articular cartilage in the medial compartment. The mean score (and standard error of the mean) for macroscopic damage to the cartilage in the group treated with the meniscectomy was 6.5+/-0.8 points compared with 3.9+/-0.7 points in the group treated with the autogenous graft and 4.3+/-0.6 points in the group treated with the allograft (p<0.05). The size of the area of damaged articular cartilage was reduced by approximately 50 percent in both groups treated with a meniscal transplant compared with the group treated with the meniscectomy (p<0.05). There were no significant differences between the group treated with the autogenous graft and that treated with the allograft. The histological appearance of the meniscal autogenous grafts was within normal limits. Interestingly, all of the allografts had evidence of fibrinoid degeneration with areas of hypocellularity and cloning of chondroid cells. CONCLUSIONS: These results suggest that meniscal transplantation provides noticeable although not complete protection against damage to the articular cartilage after a meniscectomy. The meniscal allografts were just as effective in providing this protection as were the meniscal autogenous grafts.

Animals↗
PubMed1999

Staphylococcus aureus stimulates inducible nitric oxide synthase in articular cartilage.

OBJECTIVE: To determine if Staphylococcus aureus stimulates the L-arginine-nitric oxide (NO) synthase pathway in articular cartilage. METHODS: A heat-killed and sonicated (denatured) S. aureus preparation was added to cultures of bovine articular cartilage. NO production was measured as accumulated nitrite in the culture medium and by the NO synthase-dependent conversion of 3H-L-arginine to 3H-L-citrulline in cartilage homogenates. Inducible NO synthase (iNOS) messenger RNA (mRNA) expression was analyzed by Northern blot. Proteoglycan synthesis was measured by 35SO4 incorporation into glycosaminoglycan. RESULTS: Nitrite accumulation and 3H-L-citrulline formation in cartilage were elevated by denatured S. aureus (compared with unstimulated control cartilage) and inhibited by the NO synthase inhibitor N(G)-monomethyl-L-arginine. Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S. aureus stimulation. Denatured S. aureus suppressed the accumulation of 35SO4-labeled macromolecules representing newly synthesized proteoglycans in bovine articular cartilage. The suppressed proteoglycan synthesis was due to the presence of NO. CONCLUSION: These findings support the hypothesis that a component of S. aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis.

Animals↗
PubMed1998

A logical coronal pattern classification of 2,000 consecutive idiopathic scoliosis cases based on the scoliosis research society-defined apical vertebra.

STUDY DESIGN: Two thousand consecutive idiopathic scoliosis records and radiographs were reviewed for coronal pattern typing and categorization, based on Scoliosis Research Society definitions of the apical vertebra. Apical frequency was determined for each of the patterns identified, and represents a database from a large series of cases for the already accepted Scoliosis Research Society definitions. OBJECTIVES: To identify and numerically pattern-type a large series of idiopathic coronal curves, for the basic purpose of written and oral communication. Some pattern types were not described previously. SUMMARY OF BACKGROUND DATA: Although spinal deformity must be considered three dimensional for treatment in 1998, no comprehensive, databased, and user friendly coronal or sagittal classification of idiopathic scoliosis has been reported. METHODS: Two thousand idiopathic curve patterns from charts and radiographs were reviewed and the coronal patterns categorized by the apical vertebra. The resulting classification was tested for inter- and intraobserver reliability by 12 spine surgeons and 6 orthopedic residents. Apical frequencies were determined for each pattern type. RESULTS: Twenty-one pattern categories were identified, and all were right or left mirror image patterns (except for a quadruple pattern) that permitted separation into 11 types. Incorporating the widely recognized five numbered King types mad pattern recognition simple. Interobserver reliability testing was 98.2%. The left single thoracic curve pattern was included in this classification because only 9 (20.4%) of 44 patients with left thoracic curves had intraspinal pathology. CONCLUSION: Two thousand consecutive idiopathic coronal curve patterns separated into eleven readily identifiable types, and incorporating the widely referenced five King types, makes recognition simple for purposes of identification and communication. Sagittal and 3D factors excluded from this classification are equally important in the process of treatment decisions. Apical frequency data determined in this study lends credence to Scoliosis Research Society definitions for idiopathic curve patterns.

Adolescent↗
PubMed1998

Solubility study of albumin solders for laser tissue-welding.

BACKGROUND/OBJECTIVE: Current albumin solders for tissue-welding are soluble in physiological fluids, prior to laser irradiation. These solders are therefore subjected to mechanical alterations, which can weaken the solder-tissue repair. In this study, an albumin solder (laser activated) was developed with low solubility and with the ability to retain (partially) its mechanical characteristics in saline solution. STUDY DESIGN/MATERIALS AND METHODS: Gauged protein samples of solder were immersed into 0.5 ml saline solution for fixed intervals of time. The solder samples contained four bovine serum albumin (BSA) concentrations: 56%, 66%, 70%, and 75% (by weight). A Bradford protein assay measured the BSA solubility of the solders. The 70% and 75% BSA solders were also used to weld in vitro Wistar rat intestine sections with a diode laser (lambda = 810 nm, power = 270 mW). RESULTS: The solubility of the 75% BSA solder was significantly decreased with respect to the other solders (Anova, P < 0.05). This solder also showed comparable weld strength (13 gm) to the 70% BSA solder. CONCLUSION: The 75% BSA solder strongly reduced the albumin solubility in saline solution, without affecting its tissue-welding properties.

Analysis of Variance↗
PubMed1998

Nitric oxide in arthritis.

Nitric oxide's (NO) involvement in arthritis was first demonstrated when levels of nitrite, a stable endproduct of NO metabolism, were shown to be elevated in serum and synovial fluid samples of rheumatoid and osteoarthritis patients. NO production by chondrocytes, its involvement in various biochemical events of cartilage metabolism, and the in vivo suppression of experimental arthritis by NO synthase inhibitors further implicated NO in arthritis. However, a conclusive role for NO in the pathogenesis of arthritis remains to be defined, in contrast to the NO-cGMP signal transduction pathway of endothelium-mediated vasodilation. It appears that NO has limited modulating effects in cartilage metabolism, with evidence for both protective and deleterious effects. Recent developments that contribute to our understanding of NO's role in arthritis are discussed.

Animals↗
PubMed1998

Familial slipped capital femoral epiphysis: a report and considerations in management.

BACKGROUND: Familial inheritance of slipped capital femoral epiphysis (SCFE) is known. It has not been described in non-identical twins. A family where the mother and three of five siblings developed SCFE were investigated and managed. METHODS: Anthropometric measurement consisted of height-weight ratios. Serum sex hormone levels and bone Gla Protein was measured. Bone mineral densities were evaluated. RESULTS: The affected siblings had higher bodyweight percentiles. Other investigations were within normal limits. CONCLUSION: The unfavourable height-to-weight ratio was one of the mainstays in developing a management protocol for all siblings. The management protocol developed for the family is discussed.

Algorithms↗
PubMed1998

Effects of exercise on Achilles tendon healing in a rat model.

The effects of motion, or lack of it, on Achilles tendon healing are not well defined. We have recently shown that immobilization has a detrimental effect on tendon healing in a rat model. The aim of this experiment was to determine whether enforced exercise had an additional beneficial effect on the mechanical and functional recovery of divided Achilles tendons in rats. Male Sprague-Dawley rats were randomly allocated into a nonexercise and an exercise group (N = 10 for each group). In both groups the right Achilles tendon was surgically transected. The left, uninjured lower limb served as an internal control. Both groups of animals were housed under identical conditions with the exception that the exercise group swam for 15 minutes per day. Functional performance was determined from the measurement of hindpaw prints of walking rats preoperatively and on alternate postoperative days. On day 15, the animals were killed and weighed, and biomechanical evaluations were performed on both the injured and uninjured Achilles tendon constructs. There were no differences in weight at time of death. All animals had an initial functional deficit that returned to near-normal by day 15. There were significant differences in the morphological and the mechanical properties of the healing Achilles tendon constructs at day 15 when comparing the injured with the uninjured Achilles tendon constructs. Supplemental exercise, however, had no effect on the functional or mechanical recovery of injured or uninjured Achilles tendons in the rat model.

Achilles Tendon↗
PubMed1997

Modulation of tendon healing by nitric oxide.

Nitric oxide (NO) is a small, diffusible free radical that is generated from L-arginine by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO in tendon healing. NO synthase activity and immunoreactivity was absent in un-injured rat Achilles tendon. After surgical division there was a five-fold increase in NO synthase activity and immunoreactivity within the healing tendon at day 7, with a return to near baseline levels at day 14. Inhibition of NO synthase activity with oral administration of N omega-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in cross-sectional area (30% at day 7, p < 0.01, 50% at day 15, p < 0.001) and failure load (24% at day 7, p < 0.01) of the healing Achilles tendon constructs. Rats fed the same regimen of the enantiomer of L-NAME, (D-NAME) had normal tendon healing. These results indicate that nitric oxide synthase is induced during tendon healing and inhibition of nitric oxide synthase inhibits this tendon healing.

Achilles Tendon↗
PubMed1996

S-substituted isothioureas are potent inhibitors of nitric oxide biosynthesis in cartilage.

Nitric oxide (NO.) is a multifunctional messenger molecule generated by a family of enzymes, the nitric oxide synthases, and is overproduced in osteoarthritis and rheumatoid arthritis. Chondrocytes are the major native source of NO. in diarthrodial joints. Chondrocytic inducible nitric oxide synthase induced by inflammatory cytokines and bacterial cell wall fragments mediates many of the catabolic events in arthritis. Agents which specifically inhibit chondrocyte inducible NO. synthase, may thus have a role in the management in arthritis. We evaluated a novel class of potential inducible NO. synthase inhibitors, the S-substituted isothioureas, for their ability to inhibit inducible NO. synthase activity in cultured bovine chondrocytes and explants of cartilage from patients with osteoarthritis. Two isothioureas, S-methyl isothiourea and S-(aminoethyl) isothiourea were 2-4 times more potent than NG-monomethyl-L-arginine monoacetate, 5-10 times more potent than aminoguanidine and over 300 times more potent than N omega-nitro-L-arginine and N omega-nitro-L-arginine methyl ester. The rank order of potency of the NO. synthase inhibitors was S-(aminoethyl) isothiourea > S-methyl isothiourea > NG-monomethyl-L-arginine > aminoguanidine > N omega-nitro-L-arginine = N omega-nitro-L-arginine methyl ester. The order of potency was reversed (N omega-nitro-L-arginine methyl ester = N omega-nitro-L-arginine > NG-monomethyl-L-arginine = S-methyl isothiourea > S-(aminoethyl) isothiourea > aminoguanidine) when evaluating the same compounds ability to inhibit constitutive NO. synthase activity in bovine endothelial cells. In comparison to conventional arginine based analogs, the isothioureas represent a more potent and relatively specific class of inhibitors of inducible NO. synthase in cartilage and thus may be beneficial in the management of arthritis.

Animals↗
PubMed1996

Nitric oxide enhances cyclooxygenase activity in articular cartilage.

Nitric oxide (NO) is a small messenger molecule synthesized by a family of enzymes, the nitric oxide synthases. Cyclooxygenases are a group of proinflammatory enzymes that release prostaglandins including prostaglandin E2 (PGE2). Both nitric oxide synthase and cyclooxygenase are involved in the inflammatory cascade of arthritis. However, the relationship between these two enzymes and their products has not been explored in articular cartilage. Here we show that in cultured bovine chondrocytes and explants of human osteoarthritic cartilage both nitric oxide synthase and cyclooxygenase activities were induced by the inflammatory mediators, lipopolysaccharide, and interleukin-1 beta or tumor necrosis factor-alpha. When nitric oxide synthase activity was inhibited, PGE2, synthesis was inhibited. NO donors also induced PGE2 synthesis and NO scavengers inhibited cyclooxygenase activity. Taken together, these results support the concept that PGE2 synthesis is directly related to NO formation and that NO may modulate cyclooxygenase activity in articular cartilage.

Animals↗
PubMed1996

Nitric oxide inhibitor L-NAME suppresses mechanically induced bone formation in rats.

We hypothesized that nitric oxide may act as an intermediary in the transduction of mechanical loading of bone into a bone formation response. In the present study, 48 rats were divided into the following three treatment groups: control, treatment with N omega-nitro-L-arginine methyl ester (L-NAME; an inhibitor of nitric oxide synthase), and treatment with D-NAME (the less active enantiomer of L-NAME). The rats were subdivided into groups subjected to four-point bending or sham loading of their right tibiae. Bone formation was measured at the midshaft of the loaded and nonloaded (left) tibiae of each rat using histomorphometric methods. The application of four-point bending, but not sham loading, resulted in new bone formation. Treatment with L-NAME reduced the rate of mechanically induced bone formation by 66% compared with the control group. Bone formation rates in nonloaded or sham-loaded limbs were not affected by L-NAME treatment. The results suggest that nitric oxide may play a role in the transduction of a mechanical stimulus into a biological response in bone.

Animals↗
PubMed1996

Nitric oxide: an important articular free radical.

Nitric oxide is a small molecule that is synthesized by a family of enzymes, the nitric oxide synthases, and is overproduced in rheumatoid arthritis and osteoarthrosis. The aim of this investigation was to elucidate the potential sources of nitric oxide in joint tissues and to determine if the production of nitric oxide could be inhibited by dexamethasone or methotrexate, two agents that inhibit other forms of inducible nitric oxide synthase. Methotrexate inhibits the synthesis of biopterin, which is a co-factor for nitric oxide synthase. Explants of human and bovine cartilage and cultured chondrocytes released large amounts of nitrite, the stable end product of nitric oxide, when stimulated with endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha. The production of nitrite was time-dependent and endotoxin, interleukin-1 beta, and tumor necrosis factor-alpha dose-dependent and was inhibited by the nitric-oxide-synthase inhibitors N omega-nitro-L-arginine methyl ester and aminoguanidine. The inducible nitric oxide synthase in bovine chondrocytes was calcium-dependent and was inhibited by high concentrations of methotrexate or dexamethasone. No constitutive nitric-oxide-synthase activity and little or no inducible nitric-oxide-synthase activity were demonstrable in explants or cell cultures derived from menisci. Fresh explants of bovine articular synovial tissue constitutively released nitrite that was inhibited by N omega-nitro-L-arginine methyl ester, but the release could not be enhanced by endotoxin, interleukin-1 beta, or tumor necrosis factor-alpha. There was no constitutive or inducible production of nitrite by explants or cells derived from the synovial tissue or shoulder capsule of a human or by explants or cells derived from canine anterior cruciate, posterior cruciate, medial collateral, lateral collateral, or patellar ligaments. Taken together, these results indicate that chondrocytes represent the major source of inducible nitric oxide synthase and nitric oxide during inflammation or infection of a joint.

Animals↗
PubMed1995

Nitric oxide activates metalloprotease enzymes in articular cartilage.

Nitric oxide (NO.) is a multifunctional messenger molecule generated by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in the modulation of two metal-dependent proteolytic enzymes (collagenase and stromelysin) which are activated during inflammatory and infective arthritis. The inflammatory mediators interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and the bacterial cell wall fragment endotoxin, induced both nitric oxide synthase activity and stromelysin and collagenase activity in whole cell preparations and in conditioned media from explants of bovine and human cartilage. Both NO2- (the stable end-product of NO.) and metalloprotease activity were inhibited by competitive inhibitors of nitric oxide synthase. The NO. donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP) also induced metalloprotease activity in a dose-dependent fashion. These data provide evidence that NO. plays a regulatory role in the activation of metal-dependent proteases in articular chondrocytes and cartilage.

Amino Acid Oxidoreductases↗
PubMed1995

Efficacy of recombinant human manganese superoxide dismutase compared to allopurinol in protection of ischemic skeletal muscle against "no-reflow".

A growing body of experimental data indicates that the "no-reflow" phenomenon is a type of reperfusion injury in skeletal muscle which may, in part, be mediated by oxygen free radicals, and thus may be attenuated by using agents that scavenge or inhibit formation of these reactive oxygen metabolites. This study was undertaken to assess the efficacy of recombinant human manganese superoxide dismutase (rhMnSOD) in reducing reperfusion injury in skeletal muscle. The specific advantage of this agent over other SOD types is a much longer plasma half-life (5 to 7 hr), allowing better equilibration between extra- and intracellular compartments. The rat cremaster model was used to study "no-reflow" in skeletal muscle. Reperfusion injury in the muscle was assessed by fluorescein dye perfusion, myocyte creatine phosphokinase (CPK) release, and contractile function in response to electrical field stimulation. Compared with untreated saline control animals, those treated with rhMnSOD after 5 hr of cremasteric ischemia, had a significantly higher percentage area of blood reflow (78 percent +/- 6 percent of normal), a greater percentage tetanic (66 percent +/- 9 percent of normal) and twitch (56 percent +/- 9 percent of normal) contractile strength, and less CPK release (21.5 percent higher than pre-reperfusion baseline CPK levels) (p < 0.05). Untreated saline control CPK release (21.5 percent higher than the prereperfusion level. Animals treated with allopurinol also had a significantly higher percentage twitch contraction (47 percent +/- 14 percent of normal) and a lower CPK release (11.1 percent of the prereperfusion value) 45 min after reperfusion than untreated saline controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1995

Interlocked supracondylar intramedullary nails for supracondylar fractures after total knee arthroplasty. A new treatment method.

Supracondylar fractures in patients with total knee prostheses are challenging surgical problems for which there has been no single satisfactory method of management. The authors present four cases to show that a fully cannulated, closed-section, stainless steel supracondylar intramedullary nail can be inserted in a closed fashion through a 3 cm longitudinal patellar splitting incision between the metal condyles of a nonconstrained femoral component of a total knee prosthesis. The nail can be interlocked with percutaneous screws and provides primary stability of a supracondylar femoral fracture, even in the presence of total knee and total hip prostheses.

Aged↗
PubMed1995

The surgical treatment of posterior shoulder instability.

Operative procedures for recurrent posterior instability range from glenoid osteotomy, posterior bone block procedures, posterior capsular plication with biceps tenodesis to arthroscopic stabilization with a biodegradable tac. The best results and the most commonly reported procedure(s) involve the reattachment of any labral detachment and a posterior capsular plication via a posterior approach.

Arm Injuries↗
PubMed1994

Effects of immobilization on Achilles tendon healing in a rat model.

The aim of this study was to evaluate the effects of immobilization and mobilization on the functional and biomechanical recovery of injured Achilles tendons. Male Sprague-Dawley rats were allocated randomly into four groups: (a) sham operation, (b) division only (surgical transection of the Achilles tendon without immobilization), (c) "dummy" external fixation (division of the Achilles tendon and application of Kirschner wires), and (d) rigid external fixation (division of the Achilles tendon and immobilization with Kirschner wires connected by two triangular frames). All procedures were performed on the right lower limb; the left, uninjured, lower limb served as an internal control. Kirschner wires and external fixators were removed on day 12. Functional performance was determined from measurements of hind pawprints of rats walking preoperatively and on postoperative days 1, 3, 5, 7, 9, 11, 13, and 15. On day 15, the animals were killed and biomechanical evaluations were performed on both the injured and the uninjured Achilles tendon constructs. No functional or mechanical deficits were observed in the sham-operation group. Animals subjected to division of the Achilles tendon had an initial functional deficit that returned to near normal by day 15. The application of Kirschner wires was associated with an impairment of the functional performance of the rat as well as of the mechanical properties of the tendon-bone constructs. Immobilization by connection of the Kirschner wires to an external frame had an additional, highly significant (p < 0.001) detrimental effect on the functional and mechanical recovery of Achilles tendon-calcaneal complexes.

Achilles Tendon↗