Biomedical subjects

J Antoniou

Publications and source records attributed to J Antoniou.

At least 19 recordsLinked to original sources

PubMed2006

The involvement of aggrecan polymorphism in degeneration of human intervertebral disc and articular cartilage.

The functions of the intervertebral disc and of articular cartilage are intimately related to their aggrecan content. Aggrecan is a proteoglycan that interacts with hyaluronan to form large aggregates, which are responsible for the ability of the tissues to resist compressive loads. This function is related to the structure of aggrecan, and in particular to the large number of chondroitin sulphate chains present on its core protein. The chondroitin sulphate chains are present in two adjacent regions of the aggrecan core protein, termed the CS1 and CS2 domains. In the human, the region of the aggrecan gene encoding the CS1 domain exhibits size polymorphism, which can result in variation in the degree of chondroitin sulphate substitution of aggrecan in different individuals. This raises the possibility that the functional properties of aggrecan may vary between individuals, and that those individuals with an inferior aggrecan structure may be more susceptible to premature intervertebral disc or articular cartilage degeneration. Several studies have been performed to demonstrate such an association, but the results have been ambiguous. This review explains the relationship between aggrecan structure and function, describes the technique used to assess aggrecan polymorphism and the conclusions and limitations of the data obtained to date, and discusses the implications for tissue degeneration and clinical practice.

Aggrecans↗

PubMed2005

Amifostine and dexrazoxane enhance the rapid loss of bone mass and further deterioration of vertebrae architecture in female rats.

Doxorubicin (DOX) is widely used in combination cocktails for treatment of childhood hematologic cancers and solid tumors. A major factor limiting DOX usage is DOX-induced cardiotoxicity. Dexrazoxane (DXR) is an iron-binding compound and the only approved cardioprotectant for use with DOX. Amifostine (AMF) is a free radical scavenger and approved as a broad-spectrum cytoprotectant. We have shown that when female rats are treated with AMF, AMF + DOX, or AMF + DXR + DOX there is a significant decrease in the right femoral and lumbar vertebral bone mineral density (BMD) (P < 0.05) but not in the left femoral BMD. Furthermore, the relative bone volume (BV/TV) was significantly smaller in the lumbar vertebral bodies of rats treated with AMF (21.1%), AMF + DOX (34.4%), and AMF + DXR + DOX (38.4%), as was the trabecular number (Tb.N) with AMF (15.5%), AMF + DOX (29.9%), and AMF + DXR + DOX (32.3%). AMF + DOX- and AMF + DXR + DOX-treated vertebrae also exhibited deterioration in the microarchitecture of the trabecular bone and spinous processes as ascertained by microcomputerized tomography (micro CT). This information will be useful in designing better cancer combination therapies that do not lead to bone deterioration.

Amifostine↗

PubMed2005

Assessment of compressive modulus, hydraulic permeability and matrix content of trypsin-treated nucleus pulposus using quantitative MRI.

A clinical strength MRI and intact bovine caudal intervertebral discs were used to test the hypotheses that (1) mechanical loading and trypsin treatment induce changes in NMR parameters, mechanical properties and biochemical contents; and (2) mechanical properties are quantitatively related to NMR parameters. MRI acquisitions, confined compression stress-relaxation experiments, and biochemical assays were applied to determine the NMR parameters (relaxation times T1 and T2, magnetization transfer ratio (MTR) and diffusion trace (TrD)), mechanical properties (compressive modulus H(A0) and hydraulic permeability k(0)), and biochemical contents (H(2)O, proteoglycan and total collagen) of nucleus pulposus tissue from bovine caudal discs subjected to one of two injections and one of two mechanical loading conditions. Significant correlations were found between k(0) and T1 (r=0.75,p=0.03), T2 (r=0.78, p=0.02), and TrD (r=0.85, p=0.007). A trend was found between H(A0) and TrD (r=0.56, p=0.12). However, loading decreased these correlations (r=0.4, p=0.2). The significant effect of trypsin treatment on mechanical properties, but not on NMR parameters, may suggest that mechanical properties are more sensitive to the structural changes induced by trypsin treatment. The significant effect of loading on T1 and T2, but not on H(A0) or k(0), may suggest that NMR parameters are more sensitive to the changes in water content enhanced by loading. We conclude that MRI offers promise as a sensitive and non-invasive technique for describing alterations in material properties of intervertebral disc nucleus, and our results demonstrate that the hydraulic permeability correlated more strongly to the quantitative NMR parameters than did the compressive modulus; however, more studies are necessary to more precisely characterize these relationships.

Animals↗

PubMed2004

Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc.

Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

Adolescent↗

PubMed2004

Gender-dependent reductions in vertebrae length, bone mineral density and content by doxorubicin are not reduced by dexrazoxane in young rats: effect on growth plate and intervertebral discs.

Doxorubicin (DOX) is widely used in anti-cancer cocktails. Dexrazoxane (DXR) is a cardioprotectant approved for use with DOX. The effect of DOX, with or without DXR, on bone in children is not well understood. The aim of this study was to examine the effect of DOX on vertebrae and femur length and bone density acquisition in young rats, as well as to test the hypothesis that young females are more susceptible to DOX-induced tissue damage than young males. The results of this study suggest that a single injection of DOX in young female and not male rats is associated with low bone turnover resulting in vertebrae and femur bone growth deficits. DOX selectively decreased BMD and BMC accrual in the lumbar vertebrae that was not prevented by DXR. DOX-treated rats also exhibited growth plate and intervertebral disc defects. This information will be useful in the design of interventions to promote bone growth or retard bone loss during DOX treatment.

Age Factors↗

PubMed2002

A biological approach to treating disc degeneration: not for today, but maybe for tomorrow.

The intervertebral disc unites the vertebrae in the spine, providing the flexibility required for bending and twisting and resisting the compression inflicted by gravity when in an upright posture. The discs have a complex structure, with the outer annulus fibrosus having lamellae of organized collagen fibrils and the inner nucleus pulposus having a more random collagen organization and an abundance of aggregating proteoglycans. This composite nature endows the disc with both the tension-resisting properties of a ligament and the compression-resisting properties of articular cartilage. Unfortunately, disc structure and function does not remain optimal throughout life, but undergoes progressive degeneration, commencing in the young adult, and is particularly evident in the nucleus pulposus. With time, disc degeneration may result in clinical symptoms, such as low back pain, and require medical intervention. Such treatment may involve removal of the offending disc by surgery rather than its repair, which would be the preferred course of action. In the near future, current bioengineering techniques may offer the possibility of repairing the damaged disc, if an engineered tissue with the appropriate functional properties can be generated to augment the ailing disc. In this report, we summarized our recent results, in which disc cells were implanted into a scaffold of collagen and hyaluronan, or entrapped into a chitosan gel, and growth factors were used to modulate matrix synthesis in an attempt to produce a tissue with a similar molecular composition to native nucleus pulposus tissue.

Cell Transplantation↗

PubMed2002

The role of proteoglycans in aging, degeneration and repair of the intervertebral disc.

The ability of the nucleus pulposus of the intervertebral disc to resist compressive loads is due to its high content of the proteoglycan aggrecan. Degeneration of the intervertebral disc is preceded and accompanied by a loss of aggrecan due to proteolysis. Biological repair of intervertebral disc degeneration should strive to restore aggrecan content to its optimal functional level. One approach to such repair is to supplement the degenerate nucleus with cells that are capable of aggrecan synthesis. Such cells can be supported in a biomolecular scaffold, but it is essential that the scaffold is compatible with high aggrecan retention if a functional tissue is to be attained.

Aggrecans↗

PubMed2001

Elevated synthetic activity in the convex side of scoliotic intervertebral discs and endplates compared with normal tissues.

STUDY DESIGN: We measured concentrations of specific molecules reflecting matrix synthesis and degradation in normal and scoliotic intervertebral discs and endplates. OBJECTIVES: The aim of this work was to quantitate markers of matrix turnover in normal versus adolescent idiopathic scoliotic intervertebral discs and cartilaginous endplates. SUMMARY OF BACKGROUND DATA: Changes in the intervertebral disc and endplate composition have been implicated as possible etiologic factors in the pathogenesis of adolescent idiopathic scoliosis. To better understand this process, it is important to compare the turnover of matrix components in scoliotic and normal intervertebral disc and endplate tissues. This comparison may help to improve our understanding of the role that disc and endplate tissues may play in the induction and/or progression of idiopathic scoliosis. METHODS: Fifteen scoliotic and 17 normal intervertebral discs and endplates were analyzed for their water, collagen, proteoglycan, and protein content. In addition, newly synthesized aggrecan and collagen Types I and II were measured. Percent total denatured collagen was also determined. RESULTS: The total collagen content was significantly lower in the scoliotic anulus and endplate regions, whereas glycosaminoglycan (GAG) content was significantly lower in the scoliotic endplates and nucleus regions. Conversely, total protein content was significantly higher in scoliotic endplates and elevated in scoliotic nucleus regions. Water content was significantly lower in the scoliotic anulus and endplate regions. When comparing the concave and convex regions of scoliotic endplates, there was no significant difference in concentration of any matrix component. The major difference in the synthetic marker levels relates to the synthesis of Type II collagen, which was higher in the nucleus, anulus, and endplate regions of scoliotic discs than in the corresponding regions of normal tissues. By contrast, the percent total denatured collagen was significantly elevated in the nucleus of normal tissues compared with the scoliotic ones. CONCLUSIONS: The higher collagen Type II synthetic levels and increased total protein content with no matrix turnover suggest that scoliotic changes are due to an altered and ineffective synthetic response to a pathologic mechanical environment.

Adolescent↗

PubMed2001

Posterior instability.

Posterior shoulder instability is a pathology that is increasingly seen in athletes. Excessive capsular laxity was originally proposed as the key component. Recent cadaveric and arthroscopic work has identified the importance of glenolabral integrity and glenoid depth in maintaining glenohumeral stability. Arthroscopic techniques to treat posterior instability are emerging. Until recently, reports of arthroscopic reconstruction focused entirely on capsular glenohumeral stability by altering two separate mechanisms: deepening of the glenoid concavity and reducing the capsular joint volume. This is accomplished by shifting the capsule to buttress the glenoid labrum. Thus increasing capsular tension increases the resultant compressive force vector into a deepened glenolabral concavity that, when combined together, enhances glenohumeral stability. In clinical and laboratory settings, we have shown that posteroinferior shoulder instability is associated with both capsular laxity and well-defined pathological lesions of the glenolabral concavity. Our results indicate that arthroscopic posterior capsulolabral repair and augmentation is a useful tool to restore the depth of the glenolabral concavity and to reduce the redundant posteroinferior capsule. This technique is effective in treating posteroinferior instability.

Adult↗

PubMed2001

Concussions among university football and soccer players: a pilot study.

OBJECTIVE: A pilot study to examine the incidence and characteristics of concussions for one season of university football and soccer. DESIGN: Retrospective survey. PARTICIPANTS: 60 football and 70 soccer players reporting to 1998 fall training camp. Of these, 44 football and 52 soccer players returned a completed questionnaire. MAIN OUTCOME MEASURES: Based on self-reported symptoms, calculations were made to determine the number of concussions experienced during the previous season, the duration of symptoms, the time for return to play and any associated risk factors for concussions. RESULTS: Of all the athletes who returned completed questionnaires, 34.1% of the football players and 46.2% of the soccer players had experienced symptoms of a concussion during the previous season. Only 16.7% of the concussed football players and 29.2% of the concussed soccer players realized they had suffered a concussion. All of the concussed football players and 75.0% of the concussed soccer players experienced more than one concussion during the season. The symptoms from the concussion lasted for at least 1 day in 28.6% of the football players and 18.1% of the soccer players. Variables that increased the odds of suffering a concussion during the previous season for football and soccer players included a past history of a recognized concussion. CONCLUSION: More university soccer players than football players may be experiencing sport related concussions. Variables that seem to increase the odds of suffering a concussion during the previous season for football and soccer players include a history of a recognized concussion. Despite being relatively common, many players may not recognize the symptoms of a concussion.

Adult↗

PubMed2001

Suprascapular neuropathy. Variability in the diagnosis, treatment, and outcome.

The functional outcome of operative and nonoperative treatment of suprascapular neuropathy was compared to determine the preferred method of treatment for each etiology of nerve injury. The predictive value of preoperative electromyography also was studied. Fifty-three patients were evaluated at least 1 year (average, 28 months) from the time of operative (n = 36) or nonoperative (n = 17) treatment. A modified American Shoulder and Elbow Surgeons self-assessment score was obtained at presentation and at final followup. Electromyography data were obtained at initial presentation. Minimal electromyographic changes associated with denervation were associated with a limited response to treatment, especially in patients with nerve compression secondary to spinoglenoid notch cysts. Pretreatment electromyographic findings, therefore, were predictive of treatment response. Overall, operative and nonoperative treatment of these suprascapular nerve injuries resulted in significant functional improvement, but the results varied depending on the etiology of the injury. Spinoglenoid notch cysts responded significantly better to operative treatment, with the results for open surgery being the same as the results for arthroscopic decompression. In addition, compressive lesions attributable to suprascapular notch entrapment had the best improvement with surgical decompression. Traumatic lesions, including traction and direct closed injuries, had an equal response to operative and nonoperative treatment. Overuse injuries did not improve with operative treatment. Viral neuritis improved with nonoperative treatment and never was treated with surgery. Overall, traumatic injuries resulted in significantly worse final outcomes than any other etiologic processes. In the nonoperative group, neuropathy secondary to spinoglenoid cysts resulted in significantly worse function. The outcome of treatment is dependent on the severity and etiology of the nerve injury, and the method of treatment.

Adolescent↗

PubMed2000

Collagen crosslinked N-telopeptides as markers for evaluating particulate osteolysis: a preliminary study.

The purpose of this study was to determine whether a marker of bone resorption could be used noninvasively to diagnose and assess treatment of periprosthetic osteolysis. The crosslinked N-telopeptide marker of osteoclast-mediated bone resorption potentially has the sensitivity to detect periprosthetic osteolysis. Second-morning urine specimens were obtained from (a) seven age-matched controls, (b) eight patients who had a hip arthroplasty, hybrid implants at least 1 year after surgery, and no osteolysis, (c) 11 patients who had a hip arthroplasty and osteolysis, and (d) 10 patients who had a hip arthroplasty and with osteolysis before and after 6 weeks of oral Fosamax (alendronate) treatment. The Fosamax treatment consisted of one 10-mg dose per day for 6 weeks. Men and young women (less than 40 years old) were chosen for this study to avoid bone resorption enhanced after menopause as a possible confounder. An enzyme-linked immunosorbent assay technique for quantifying crosslinked N-telopeptides of type-I collagen was performed on all specimens. The patients with osteolysis had significantly elevated levels of N-telopeptide compared with the implant control group. In addition, levels of N-telopeptide were significantly lowered after Fosamax treatment. These findings indicate that a systemic bone-resorption marker (N-telopeptide) can be used to evaluate local particulate-induced osteolysis and its treatment. The study also provides clinical evidence that osteolysis is associated with increased osteoclast-mediated bone resorption and that this locally induced bone resorption can be suppressed by certain bisphosphonates (Fosamax). These insights have potential value in the understanding and clinical management of aseptic loosening.

Adult↗

PubMed2000

Arthroscopic posterior capsular repair.

Posterior shoulder instability is associated with capsular laxity and well-defined pathologic lesions of the gleno-labral concavity. Most arthroscopic techniques have concentrated on capsular shift or plication of capsular laxity. This article demonstrates that arthroscopic capsulolabral plication simultaneously can augment the glenolabral concavity to restore the glenoid depth, and can reduce excessive capsular laxity of the redundant posteroinferior capsule. This method has proven effective in treating posterior instability.

Arthroscopy↗

PubMed2000

Capsulolabral augmentation for the the management of posteroinferior instability of the shoulder.

BACKGROUND: Posteroinferior instability of the shoulder has been associated with capsular laxity. The purposes of the present study were to describe the pathological morphology of the posteroinferior aspect of the glenolabral fossa in patients with primary posteroinferior instability and to prospectively examine the efficacy of managing this instability with use of an arthroscopic posteroinferior capsulolabral augmentation procedure. METHODS: Forty-one patients who had posteroinferior instability of the shoulder were managed with an arthroscopic shift of the posteroinferior aspect of the capsule to the adjacent labrum and were followed for a minimum of twelve months. Thirty-two patients had a primary procedure, and nine had a revision procedure. The mean duration of follow-up was twenty-eight months (range, twelve to sixty-nine months). All of the patients had presented with a symptomatic, positive finding on the jerk test and had participated in a minimum of six months of rehabilitation that had failed to relieve the symptoms. The patients were evaluated prospectively with a motion and stability examination and the Simple Shoulder Test. In addition, they completed the Short Form-36 Health Survey (SF-36) and a questionnaire on the outcome of treatment. RESULTS: Lesions affecting the posteroinferior aspect of the glenolabral concavity were seen in thirty-four patients (83 percent): five had labral detachment, seven had chondral or labral erosion, nine had capsular and synovial stripping, and thirteen had a labral split or tear. The mean score (and standard deviation) on the Simple Shoulder Test improved from 5.5 +/- 3.4 points to 8.1 +/- 3.3 points (p = 0.0023), and two of the eight SF-36 parameters improved significantly (p < 0.05). Conversely, nineteen patients who were receiving Workers' Compensation did not show any improvement in either of the two parameters. Thirty-five patients had improved stability of the shoulder, and the findings on all physical examinations had improved significantly (p < 0.0001). Twenty-eight patients had a perception of residual stiffness; this finding was in contrast to the mean score on the flexibility examination, which had not changed significantly at the time of the latest follow-up. CONCLUSIONS: Posteroinferior instability of the shoulder is associated not only with capsular laxity but also with well defined lesions of the glenolabral concavity. Arthroscopic capsulolabral augmentation to reduce posterior capsular laxity and to restore the depth of the glenolabral concavity has been shown to be effective treatment of this condition after a mean duration of follow-up of twenty-eight months.

Adult↗

PubMed2000

Osteoporosis of the spine: correlation between vertebral deformity and bone mineral density in postmenopausal women.

The purpose of this study is to evaluate the relation of bone mineral density (BMD) or the age-matched z score and osteoporotic vertebral fractures. The radiographs and spinal bone mineral density of 131 consecutive postmenopausal patients were retrospectively reviewed. The vertebral fractures between T4 and L4 were graded. Sixty-two patients had no fractures, and 69 had 1 or more fractures. In the nonfracture group, the mean age was 62.6 years, BMD was 0.88 g/cm2, and the z score was -1.00. In the fracture group, the mean age was 69.6 years, BMD was 0.788 g/cm2, and the z score was -1.26. Patients with 2 and 3 or more fractures had a lower mean BMD than that of the nonfracture group (P < .01). The z score (adjusted for age) was significantly lower only in patients with 3+ fractures (P < .05). Patients with grade 2 and grade 3 of any fracture type had significantly lower BMD (P < .01). The z score was lower only in those with grade 3 fracture (P < .05). Our study indicates that the clinical use of BMD z score adjusted for age is a better predictor of severity of vertebral fractures than is BMD alone.

Adult↗

PubMed1999

Minimum 10-year-results of extensively porous-coated stems in revision hip arthroplasty.

Obtaining predictable, stable fixation of revision femoral implants is important for the long-term success of revision hip arthroplasty. The authors report on minimum 10 years clinical and radiographic followup of 170 patients with extensively coated cementless revision femoral components. With a range of followup of 10 to 16 years and a mean of 13.2 years, a survivorship of greater than 95% was reported. Clinically, the average Postel-D'Aubigne pain and walking score improved from a preoperative score of 5.4 points to 10.8 points postoperatively. Eighty-two percent of the hips had radiographic evidence of a bone-ingrown prosthesis and 13.9% had evidence of stable fibrous fixation. Four percent of stems were unstable as seen on radiographs. Six stems were revised to larger extensively coated stems and one stem is causing pain and is unstable but has yet to be revised. The overall mechanical failure rate was 4.1%. Stress shielding was greatest in patients with stems larger than 16.5 mm and in osteoporotic bone (Dorr Type C). Nine percent of patients had significant thigh pain including all of the patients with unstable stems. In the presence of bone loss in the proximal metaphyseal region of the femur, fixation of the femoral component is predictable when optimizing prosthetic-bone fit in the diaphyseal region of the femur using an extensively coated femoral component.

Acetabulum↗

PubMed1998

Quantitative magnetic resonance imaging in the assessment of degenerative disc disease.

Understanding degenerative intervertebral disc diseases hinges on the ability to objectively and noninvasively assess the disc matrix composition and integrity. The potential of quantitative magnetic resonance imaging to meet these demands was evaluated. Analyzing the T1 and T2 signal patterns in the nucleus pulposus with increasing Thompson morphological grade revealed a significant reduction related to grade. This significant decrease in T1 and T2 in the nucleus pulposus with grade 4 degeneration and the corresponding low correlation coefficients with respect to the content of individual matrix molecules suggest that matrix integrity plays an important and distinct role in determining T1 and T2 signal. Similarly, the significant increase in magnetization transfer in the nucleus pulposus observed in grade 4 degeneration did not correlate with the changes in molecular content in these highly degenerated discs. Again, this lack of correlation clearly indicates that the tissue integrity and matrix composition independently contribute to the magnetization transfer signal. This study presents the first clear evidence that quantitative magnetic resonance analysis reflects not only the disc matrix composition, but also the structural integrity of the matrix of the disc.

Adult↗

PubMed1998

Exercise capacity in patients with beta-thalassemia major: relation to left ventricular and atrial size and function.

OBJECTIVES: The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with beta-thalassemia major. BACKGROUND: In patients with beta-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. METHODS AND RESULTS: Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (Vo 2 max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with beta-thalassemia major had reduced Vo 2 max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, Vo2 max and AT were inversely related to Vmax (r = -0.74 and r = -0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in beta-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0. 53, respectively). In the control group, Vo 2 max and AT parameters were related to Vmax and ACTEF in a similar way to that in the beta-thalassemia group. CONCLUSIONS: In patients with beta-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity.

Adolescent↗