The MMP3 gene in musculoskeletal soft tissue injury risk profiling: A study in two independent sample groups.

Matrix metalloproteinase-3 (MMP3) is a mediator of matrix remodelling and a proposed susceptibility locus in the genetic profile of musculoskeletal soft tissue injuries. Therefore, this study aimed to validate the MMP3 gene as a risk marker for these injuries by conducting a case control genetic association study in two independent samples groups. Three previously investigated MMP3 variants (rs679620, rs591058 and rs650108) in addition to the functional promoter variant (rs3025058) were genotyped in 195 Australian control participants and 79 Australian individuals with chronic Achilles tendinopathy. Similarly, 234 South African individuals with acute anterior cruciate ligament ruptures and 232 matched control participants were also analysed. Based on high linkage with the previously associated MMP3 variant rs679620, rs3025058 was inferred and found to be associated with increased risk for Achilles tendinopathy within the South African group (P = 0.012; OR: 2.88; 95% CI: 1.4 to 6.1). Lastly, the 6A-G-C-G haplotype, constructed from the investigated variants, was significantly associated with reduced risk for Achilles tendinopathy (29% CON vs. 20% TEN, P = 0.037) in the Australian group. In conclusion, a signal surrounding MMP3 is apparent with respect to Achilles tendinopathy. However, whether the investigated variants are contributing to injury susceptibility or whether they are merely linked to the risk conferring variants mapping elsewhere within the MMP gene cluster on chromosome 11, still requires refining.

Computational modelling of mobile bearing TKA anterior-posterior dislocation.

Anterior-posterior stability in an unconstrained mobile-bearing total knee arthroplasty (TKA) and one with rotational constraints is compared in a computational model based on an ASTM test. Both TKA designs dislocate at loads greater than reported maximum in vivo forces. The posterior drawer forces (mean: 3027 N vs. 1817 N) needed to induce subluxation increase with a greater anterior jump distance (12 mm vs. 7 mm; refers to the vertical height of the anterior or posterior border of the tibial insert's articulating surface). The posterior jump distance for both tested TKA differed by 1.5 mm and had minimal effect on the magnitude of the anterior drawer forces at dislocation in mid-flexion (unconstrained vs. constrained: 445 N vs. 412 N). The unconstrained insert dislocated by means of spin-out whereas in the constrained TKA the femur dislocated from the bearing during posterior drawer and the bearing from the baseplate during anterior drawer. MCL function is an important consideration during ligament balancing since a ± 10% variation in MCL tension affects dislocation forces by ± 20%. The simulation platform provided the means to investigate TKA designs in terms of anterior-posterior stability as a function of knee flexion, collateral ligament function and mechanical morphology.

ELN and FBN2 gene variants as risk factors for two sports-related musculoskeletal injuries.

The proteins ELN and FBN2 are important in extracellular matrix function. The ELN rs2071307 and FBN2 rs331079 gene variants have been associated with soft tissue pathologies. We aimed to determine whether these variants were predisposing factors for both Achilles tendinopathy (AT) and anterior cruciate ligament (ACL) ruptures. For the AT study, 135 cases (TEN group) and 239 asymptomatic controls were recruited. For the ACL rupture study our cohort consisted of 141 cases (ACL group) and 219 controls. Samples were genotyped for both the ELN rs2071307 and FBN2 rs331079 variants using TaqMan assays. Analysis of variance and chi-squared tests were used to determine whether either variant was associated with AT or ACL rupture with significance set at p<0.05. The GG genotype of the FBN2 variant was significantly over-represented within the TEN group (p=0.035; OR=1.83; 95% CI 1.04-3.25) compared to the CON group. We also found that the frequency of the G allele was significantly different between the TEN (p=0.017; OR=1.90; 95% CI 1.11-3.27) and ACL groups (p=0.047; OR=1.76; 95% CI 1.00-3.10) compared to controls. The ELN rs207137 variant was not associated with either AT or ACL rupture. In conclusion, DNA sequence variation within the FBN2 gene is associated with both AT and ACL rupture.

The GDF5 gene and anterior cruciate ligament rupture.

A recent genetic association study has revealed that a variant (rs143383) within the 5'-untranslated region of the growth differentiation factor 5 gene (GDF5) associates with the risk of Achilles tendon pathology. The aim of this study was to determine whether this variant associates with the risk of ACL rupture. A cohort of 126 Caucasians with ACL rupture (ACL group), including 51 subjects who ruptured their ACL through a non-contact mechanism (NON sub-group), and 214 controls (CON group) were genotyped for the rs143383 variant. We report no significant GDF5 rs143383 genotype (P=0.396) or allele (P=0.810) frequency differences between the ACL (TT genotype, n=37, 29%; CT genotype, n=72, 57%; CC genotype, n=17, 14%) and CON (TT genotype, n=73, 34%; CT genotype, n=106, 50%; CC genotype, n=35, 16%) groups. There were also no significant differences between the NON sub-group and the CON group (allele; P=0.710, genotype; P=0.771). Furthermore, in gender specific analysis we found no association between rs143383 and ACL in either males (allele; P=0.988, genotype; P=0.407) or females (allele; P=0.643, genotype; P=0.885), respectively. Nor were there any gender specific associations between the NON sub-group and either genotype or allele. In conclusion, the rs143383 variant was not found to associate with the risk of ACL rupture.

Knee rotational laxity: an investigation of bilateral asymmetry for comparison with the contralateral uninjured knee.

BACKGROUND: Instability associated with anterior cruciate ligament injury is commonly evaluated against the patient's contralateral knee. The objectives of this study were, therefore, to assess symmetry of rotational knee laxity in vivo under passive torsional loading in uninjured subjects, and to compare mean rotation of this control group with the contralateral, intact knees of anterior cruciate ligament deficient patients. METHODS: Axial knee rotation was measured in 29 patients with unilateral anterior cruciate ligament injury and 15 uninjured age and gender-matched control subjects using an imaging-compatible torsional loading device. Side-to-side differences in internal, external, and range of knee rotation were assessed in the control group and mean bilateral knee rotation was compared to the patients' contralateral knee data at both full extension and 30° of flexion. FINDINGS: Statistically significant differences in symmetry were found in three of the six measures of transverse plane rotation in the uninjured knees; a mean side-to-side difference of 2.2° in range of rotation was detected in the flexed position. No significant differences were observed between the mean values of the healthy control group and the contralateral knees of the anterior cruciate ligament deficient patients. INTERPRETATION: Bilateral asymmetry of rotational laxity occurs in healthy individuals. Nevertheless, comparability of rotational knee laxity between the contralateral limbs of patients and the uninjured population was evidence that rotational laxity was not inherent or developed in the contralateral knees of the anterior cruciate ligament deficient participants.

Matrix metalloproteinase genes on chromosome 11q22 and the risk of anterior cruciate ligament (ACL) rupture.

As matrix metalloproteinases (MMPs) are critical to ligament homeostasis and integrity, the aim of this study was to investigate whether four functional polymorphisms within four MMP genes, which cluster on chromosome 11q22 associate with risk of ACL ruptures. Three hundred and forty-five [129 with ACL ruptures (ACL group) and 216 asymptomatic controls (CON group)] unrelated Caucasians were recruited for this case-control study. Fifty-four participants reported non-contact mechanisms of ACL rupture (NON subgroup). All participants were genotyped for the MMP10 C/T rs486055, MMP1 1G/2G rs1799750, MMP3 G/A rs679620 and MMP12 A/G rs2276109 variants. After adjusting for sex, age and weight, the AG and GG genotypes of the MMP12 rs2276109 variant were significantly (P=0.030) under-represented among the NON subgroup (14%), when compared with the CON group (26%). No other variants were significantly different between groups. Adjusted for the same confounders, the two four-variant haplotypes T-1G-A-A (CON 14%, ACL 9%, P=0.033) and C-2G-G-G (CON 14%, NON 5%, P=0.021) were significantly different between the CON and the ACL groups, and the CON group and the NON subgroup, respectively. This is the first report that indicates an association between the chromosomal region 11q22 and the risk of ACL rupture.

Double-bundle ACL surgery demonstrates superior rotational kinematics to single-bundle technique during dynamic task.

BACKGROUND: While traditional surgical repair of the anterior cruciate ligament is able to restore anterior-posterior knee stability, laxity in the transverse plane remains. Double-bundle reconstruction has demonstrated greater rotational restraint than the single-bundle technique under passive loading conditions; however, no comparison has been made under physiological weight-bearing conditions. The purpose of this study was to determine differences in rotational knee kinematics during a dynamic task in patients who had received either a single- or double-bundle reconstruction. METHODS: Twenty-two patients exhibiting isolated anterior cruciate ligament rupture were randomly allocated either a single or double-bundle reconstruction. Three-dimensional knee kinematics were measured during a dynamic cutting activity prior to and following surgery. Functional range of rotation was compared between groups pre- and post-operatively and kinematics were assessed against uninjured control subjects. FINDINGS: No difference in overall range of rotation was found under physiological loading conditions. However, a significant interaction of the midpoint of the range of movement was observed; a greater external rotational shift in the single-bundle group followed reconstruction, while the kinematics of the double-bundle patient group shifted closer to those of the control group. INTERPRETATION: The double-bundle reconstruction demonstrated superior outcome in rotational kinematics to the single-bundle technique.

Genetic risk factors for anterior cruciate ligament ruptures: COL1A1 gene variant.

BACKGROUND: Anterior cruciate ligament (ACL) ruptures are considered the most severe injury sustained in sports. Although various intrinsic and extrinsic risk factors have been identified, the exact aetiology of the injury is not yet fully understood. Recently, the gene encoding for the alpha1 chain of type I collagen (COL1A1) has been shown to be associated with cruciate ligament ruptures and shoulder dislocations. OBJECTIVE: To determine whether the functional Sp1 binding site polymorphism within intron 1 of the COL1A1 gene is associated specifically with ACL ruptures in an independent population. METHODS: 117 Caucasian participants with surgically diagnosed ACL ruptures, and 130 Caucasian physically active controls without any history of previous ligament or tendon injuries were recruited for this case-control genetic association study. All participants were genotyped for the COL1A1 Sp1 binding site polymorphism (G/T; rs1800012). RESULTS: The rare TT genotype was significantly (p = 0.031, OR = 0.08, 95% CI <0.01 to 1.46) under-represented in the ACL group (0 out of 117, 0%), compared with the controls (6 out of 130, 4.6%). CONCLUSION: The TT genotype of the COL1A1 Sp1 binding site polymorphism was significantly under-represented in South African participants with ACL ruptures. We propose that this sequence variant be the first specific genetic element to be included in multifactorial models developed to understand the aetiology and risk factors for ACL rupture.

Measuring three-dimensional knee kinematics under torsional loading.

Excessive knee joint laxity is often used as an indicator of joint disease or injury. Clinical assessment devices are currently limited to anterior-posterior drawer measurements, while tools used to measure movement in the remaining degrees of freedom are either invasive or prone to soft tissue artefact. The objective of this work was, therefore, to develop a methodology whereby in vivo knee joint kinematics could be measured in three dimensions under torsional loading while still maintaining a non-invasive procedure. A device designed to administer a subject-normalized torque in the transverse plane of the knee was securely fastened to the outer frame of an open magnetic resonance imaging (MRI) magnet. Low resolution 3D T1-weighted images (6.25 mm slice thickness) were generated by the 0.2 Tesla MRI scanner in less than 3 min while the joint was under load. The 3D image volume was then shape-matched to a high resolution image volume (1.56 mm slice thickness) scanned in a no-load position. Three-dimensional rotations and translations of the tibia with respect to the femur were calculated by comparing the transformation matrices before and after torque was applied. Results from six subjects showed that this technique was repeatable over five trials with the knee in extended and flexed positions. Differences in range of rotation were shown between subjects and between knee positions, suggesting that this methodology has sufficient utility for further application in clinical studies.

Percutaneous endoscopic gastrostomy in children--a 5-year experience.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) has been performed on children since 1979. The indications for a PEG are wide ranging and while there are well-established benefits, it remains a procedure with recognised complications. GOALS AND OBJECTIVES: The goal of this study was to review our experience with this procedure at a South African paediatric tertiary referral hospital over a 5-year period. The objectives were to review PEGs with regard to patient characteristics, indications, anaesthesia time required and complications. METHODS: The study was a retrospective case record review. RESULTS: A total of 70 PEGs were performed. Patients had a mean age of 4 years and 3 months, and a mean weight of 12.2 kg at the time of performing the procedure. The mean anaesthetic time required for performing a PEG was 27 minutes. Fifty-four PEGs (77%) were performed for inability to swallow, 15 (21%) to improve caloric intake, and 1 (1%) for continuous enteral feeding. There were no deaths, 5 patients had major complications (6%), and 12 patients (17%) needed antireflux surgery subsequent to the placement of a PEG. DISCUSSION: There is an increasing demand for PEGs at our institution. The indications for a PEG in this series are similar to those reported in other series, although we may be underutilising PEGs to improve caloric intake. Our complication rates compare favourably with those reported in other series. We have, however, identified post-PEG gastrooesophageal reflux disease as a complication we would like to reduce, and suggest a practical approach to do so.

Modified computed tomography peritoneography: clinical utility in continuous ambulatory peritoneal dialysis patients.

The purpose of the present paper is to review the indications, results, clinical correlation and implications for management of a modified CT peritoneography (CTP) technique in the evaluation of continuous ambulatory peritoneal dialysis (CAPD) patients. Forty CTP in 33 patients were reviewed by two observers blinded to clinical history or outcome. The CTP technique included 100 mL non-ionic intraperitoneal contrast, 1 h of ambulation and prone positioning during the CT. No precontrast or delayed examinations were performed. A CAPD-related complication was diagnosed in 33 of 40 (82%) CTP. Twenty-nine CTP were performed for evaluation of suspected dialysate leaks. In this group there were 18 leaks, a total of seven umbilical hernias (five as isolated findings) and five normal studies. Nine of 18 (50%) leaks resolved with conservative management and six of nine patients (67%) of the remainder continued CAPD after appropriate surgery. Seven patients were evaluated for scrotal swelling (one bilateral), and there were five communicating hydroceles (all with inguinal fat herniation and all surgically confirmed) and three non-communicating hydroceles (none of which progressed). Umbilical hernias were present in nine of 33 patients (27%). No false positive or false negative studies were identified. The CTP technique described provides accurate diagnostic information in the management of common CAPD-related complications, particularly dialysate leak, genital swelling, abdominal wall hernias and peritoneal adhesions. Computed tomography peritoneography directs appropriate conservative or surgical management.

Diabetic muscle infarction in patients on dialysis.

Spontaneous muscle infarction in diabetic patients is a rare condition that usually occurs in those with advanced diabetic complications. There is a high prevalence of diabetic nephropathy and varying degrees of renal failure. Both type 1 and type 2 diabetics are at risk. The mean age at presentation is approximately 40 years, and both sexes are affected. The cause is uncertain but appears to be attributable to diabetic microangiopathy, with thickening of walls of small arteries and fibrinoid occlusion. There is necrosis of all elements of the muscle, with polymorphonuclear or mononuclear cellular infiltration and a varying but often limited degree of regeneration, depending on the age of the lesion. The presentation is usually acute, with pain and swelling localized to the thigh in most instances. Systemic signs such as pyrexia are infrequent. Laboratory tests (such as white cell count and creatinine kinase) and plain radiographs are not helpful, although the erythrocyte sedimentation rate is often elevated. The diagnosis, in the appropriate setting, is strongly suggested by magnetic resonance imaging, which shows increased signal intensity and asymmetry of the muscle on T2-weighted scanning as well as fluid in the tissue planes. Management consists of resting the muscle, analgesics, and gradual mobilization. Recurrence is common and may be seen in more than 50% of the patients.

Intra-operative pneumatic tourniquet--perceptions of use and complications in the orthopaedic community of South Africa.

OBJECTIVES: To assess views on use, maintenance and side-effects of the pneumatic tourniquet in the South African orthopaedic community. METHODS: A census-type questionnaire study was conducted of all 475 orthopaedic surgeons registered with the Orthopaedic Association of South Africa during 1993/94. The chi-square test was used to determine statistical significance between different groups of respondents. RESULTS: Seventy-seven per cent of the questionnaires were returned. Ninety-nine per cent of respondents used a pneumatic tourniquet. Eighty-four per cent believed that the tourniquet may damage underlying tissue both as a result of applied pressure effects and ischaemic consequences. Fifty-four per cent of respondents personally checked the calibration of the pneumatic tourniquet, although 76% of respondents believe that the apparatus needs to be checked at least once per month. More respondents who did not check the tourniquet apparatus than respondents who did check it believe that applied pressure does not cause tissue damage (P < 0.001), that the operating room technician or hospital engineer should be responsible for checking equipment (P < 0.001), and that equipment did not need to be checked more than once every 6 months (P < 0.001). CONCLUSIONS: Although most orthopaedic surgeons are aware of the pneumatic tourniquet's side-effects, a minority appear to be unaware of the hazards of excessive applied pressure alone or excessive applied pressure caused by use of faulty equipment. It needs to be emphasised to these surgeons that regular checking of the pneumatic tourniquet apparatus is necessary in order to prevent postoperative complications ascribed to use of the tourniquet.

A method of determining the corrosive properties of dental amalgams.

The purpose of this study was to determine the corrosive properties of 5 dental amalgams, using a modified rotating disk electrode method described by Van der Merwe, De Wet and Mc Crindle (1991). Ten cylindrical specimens of each amalgams were prepared according to the ISO guidelines. The amount of gamma-2 present was determined by the method employed by Sarkar and Greener (1972), while the corrosion rates were calculated from the Tafel slopes of the polarisation diagrams. All data were analysed statistically. Results showed that at day one Silvalloy contained the most gamma-2, followed by Amalgaphase (previous formulation) and Amalgaphase (new formulation). Dispersalloy and Amalga Sphere contained no gamma-2 at day one. At day nine none of the amalgams tested contained gamma-2 phase. The corrosion rates of the different groups of amalgam varied significantly (p < 0.01) as tested by ANOVA. The spherical amalgam, Amalga Sphere, showed a better corrosion resistance (p < 0.01) than the other amalgams. The method used for evaluating the corrosive properties of dental amalgam proved to be precise, rapid and simple.

Clinical evaluation of four dental amalgams over a three year period.

The aim of this study was to compare the clinical durability of four dental amalgams. In each of eighty-two patients one class 2 cavity was restored with Dispersalloy (Johnson and Johnson) which served as the control and all the other class 2 cavities were randomly restored with one of the following amalgams: Amalgaphase, Amalga 43 (Amalgam Alloys-South Africa) or Permite C (Southern Dental Industries). Matrix bands were placed and Kalzinol bases and Polyvar varnishes applied in all cavities. The amalgams were mixed according to the manufacturers' instructions, the cavities overpacked with amalgam, condensed by hand, carved and then burnished with a ball burnisher. Twenty-four hours later all restorations were polished and colour photographs taken. The restorations were evaluated using the Ryge and Snyder (1973) evaluation system, as well as comparison of the colour photographs. The Fisher's Exact Test was used for the statistical analysis. The two South African manufactured amalgams compared well with the two imported amalgams. However, at the end of the third year the score for the marginal integrity of Amalgaphase, one of the local products, was significantly different (p < 0.083) and inferior to that of the control, Dispersalloy. Evidence is produced to suggest that over a three year period Amalgaphase performed better than Dispersalloy, Amalga 43 and Permite C.

Clinical evaluation of four dental amalgams over a two year period.

The aim of this study was to determine the clinical durability of two locally manufactured amalgams. In each of eighty-two patients one class II cavity was restored with Dispersalloy (Johnson and Johnson) which served as the control and all the other class II cavities were randomly restored with one of the following amalgams: Amalgaphase, Amalga 43 (Amalgam Alloys-South Africa) or Permite C (Southern Dental Industries). Matrix bands were placed. Kalzinol bases and Polyvar varnish were applied in all cavities. All amalgams were mixed according to the manufacturers' instructions. The cavities were overpacked with amalgam, and the amalgam condensed by hand, carved and then burnished with a ball burnisher. Twenty-four hours later all restorations were polished with a Shofu polishing system and colour photographs were taken. The restorations were evaluated using the Ryge and Snyder (1973) evaluation system, as well as comparison of the colour photos. The Fisher's Exact Test was used for the statistical analysis. During the second year there were no significant (p < 0.05) differences between the four brands of amalgam restorations except as regards the gloss category. The two South African manufactured amalgams compared well with the two imported amalgams. During the second year the marginal integrity and surface texture of Amalgaphase compared well with that of Permite C. Dispersalloy and Permite C showed more deterioration in anatomic form than the two South African amalgams. Amalgaphase was the only amalgam to show no bulk fracture within a period of two years. Amalgaphase performed better in the gloss category than the other three amalgams during the second year evaluation. According to the weighted product calculation Amalgaphase was the best amalgam followed by Dispersalloy, Amalga 43 and Permite C.

Pre-operative assessment and management of the patient with ischaemic coronary artery disease in non-cardiac surgery.

Peri-operative cardiac events are the leading cause of death following anaesthesia and surgery. We attempt to put into perspective the various methods of pre-operative assessment of patients at risk, and suggest a logical sequence for the use of potentially costly investigations such as 12-lead ECG, exercise stress ECG, ambulatory ECG monitoring, myocardial perfusion imaging, radionuclide ejection fraction, and coronary angiography. Important principles are given for the management of patients at risk of peri-operative cardiac incidents if the decision is made to proceed with non-cardiac surgery despite the potential risk or because of inoperable coronary disease.