Lower-limb dominance as a possible etiologic factor in noncontact anterior cruciate ligament tears

The purpose of this study was to determine if lower-limb dominance is a potential etiologic factor in noncontact anterior cruciate ligament (ACL) tears. A multicenter retrospective case analysis was performed. In each of the participating centers, patients were questioned to confirm a noncontact ACL injury and to determine lower-limb dominance. Three hundred and two subjects (149 males and 153 females) who presented with unilateral noncontact ACL tears participated in the study. The relationships between limb dominance, side of injury, and gender were analyzed. There was no significant correlation between the side of injury and the dominant limb for kicking (p = 0.30). There was no significant gender effect of the relationship between side of injury and dominant limb (p = 0.36). When assessing gender types and side of ACL tears, females showed a strong trend toward tearing the left ACL more frequently than the right (p = 0.06). No such trend existed for males. The results of this study indicate that there is no significant relationship between lower-limb dominance and the likelihood of sustaining a noncontact ACL tear. However, the strong trend toward females tearing their left ACLs more often than their right ACLs warrants further investigation to determine what neuromuscular asymmetries may exist between the right and left lower limbs.     

Empirical relationship between lengthening an anterior cruciate ligament graft and increases in knee anterior laxity: a human cadaveric study

Lengthening of an anterior cruciate ligament (ACL) graft construct can occur as a result of lengthening at the sites of tibial and/or femoral fixation and manifests as an increase in anterior laxity. Although lengthening at the site of fixation has been measured for a variety of fixation devices, it is difficult to place these results in a clinical context because the mathematical relationship between lengthening of an ACL graft construct and anterior laxity is unknown. The purpose of our study was to determine empirically this relationship. Ten cadaveric knees were reconstructed with a double-looped tendon graft. With the knee in 25 degrees of flexion, the position of the proximal end of the graft inside the femoral tunnel was adjusted by moving the femoral fixation device until the anterior laxity at an applied anterior force of 134 N matched that of the intact knee. In random order, the graft construct was lengthened 1, 2, 3, 4, and 5 mm by moving the femoral fixation device distally along the femoral tunnel and anterior laxity was measured. The increase in the length of the graft construct was related to the increase in anterior laxity by a simple linear regression model. Lengthening the graft construct from 1 to 5 mm caused an equal increase in anterior laxity (slope=1.0 mmmm, r(2)=0.800, p<0.0001). Because an anterior laxity increase of 3 mm or greater in a reconstructed knee is considered unstable clinically and because many fixation devices in widespread use clinically allow 3 mm or greater of lengthening in in vitro tests, our empirical relationship indicates that lengthening at the site of fixation probably is an important cause of knee instability following ACL reconstructive surgery. Our empirical relation also indicates that an important criterion in the design of future fixation devices is that lengthening at the sites of fixation in in vitro tests should be limited to less than 3 mm.     

Hip and knee joint kinematics during a diagonal jump landing in anterior cruciate ligament reconstructed females

Anterior cruciate ligament (ACL) injury is a common injury encountered by sport medicine clinicians. Surgical reconstruction is the recommended treatment of choice for those athletes wishing to return to full-contact sports participation and for sports requiring multi-directional movement patterns. The aim of ACL reconstruction is to restore knee joint mechanical stability such that the athlete can return to sporting participation. However, knowledge regarding the extent to which lower limb kinematic profiles are restored following ACL reconstruction is limited. In the present study the hip and knee joint kinematic profiles of 13 ACL reconstructed (ACL-R) and 16 non-injured control subjects were investigated during the performance of a diagonal jump landing task. The ACL-R group exhibited significantly less peak knee joint flexion (P=0.01). Significant between group differences were noted for time averaged hip joint sagittal plane (P<0.05) and transverse plane (P<0.05) kinematic profiles, as well as knee joint frontal plane (P<0.05) and sagittal plane (P<0.05) kinematic profiles. These results suggest that aberrant hip and knee joint kinematic profiles are present following ACL reconstruction, which could influence future injury risk.     

Scanning electron microscopy study of the meniscus of the knee in patients with anterior cruciate ligament lesions]

In the aim of bringing a contribution to role of the knee menisci and the functional connection between meniscal lesions and knee joint instability, four patients have been studied, who underwent arthroscopy for sub-acute tear of anterior cruciate ligament without clinical or morphological evidence of meniscal pathology. In these patients biopsies have been taken from one of the menisci and processed for the examination by the SEM. As control, meniscal fragments from two healthy knees have been studied from patients who underwent amputation at thigh for accidental trauma with irreparable lesion of femoral artery. In patients affected by ligamentous tear, on the meniscal surface a lot of deposited material appears, as well as many microlesions as clefts or cracking and distortion of superficial collagenous fibers. All described alteration are more evident in the central portion of menisci than in the anterior or posterior horns. The above mentioned patterns suggest a strong correlation of the knee instability due to ligamentous lesions and meniscal degenerative process which would onset before its clinical or macroscopical evidence.     

Consequences of a ligament injury on neuromuscular function and relevance to rehabilitation - using the anterior cruciate ligament-injured knee as model.

The purpose of this article is to survey current knowledge concerning the consequences of a ligament injury on neuromuscular function and its relevance to rehabilitation, in relation to clinical practice. Although it deals with the ACL-injured knee, these views may also apply to other joints. The effects of a ligament injury on neuromuscular function are first considered - i.e., proprioception, postural control, muscle strength, functional performance, movement and activation pattern, central mechanisms, motor control and learning. The treatment and effects of rehabilitation on neuromuscular function are then discussed. The survey is concluded by discussing the clinical significance.     

Development of a traumatic anterior cruciate ligament and meniscal rupture model with a pilot in vivo study

The current study describes the development of a small animal, closed-joint model of traumatic anterior cruciate ligament (ACL) and meniscal rupture. This model can be used in future studies to investigate the roles of these acute damages on the long-term health of an injured knee joint. Forty-two Flemish Giant rabbits received an insult to the left tibiofemoral joint ex vivo in order to document optimal energy and joint orientation needed to generate ACL and meniscal rupture, without gross fracture of bone. Impact energies ranged from 10 J to 22 J, and joint flexion angle ranged from 60 deg to 90 deg. Three in vivo animals were impacted at 13 J with the knee flexed at 90 deg, as this was determined to be the optimal load and joint orientation for ACL and meniscal ruptures, and sacrificed at 12 weeks. Impact data from the ex vivo group revealed that 13 J of dropped-mass energy, generating approximately 1100 N of load on the knee, would cause ACL and meniscal ruptures, without gross bone fracture. Acute damage to the lateral and medial menisci was documented in numerous ex vivo specimens, with isolated lateral meniscal tears being more frequent than isolated medial tears in other cases. The in vivo animals showed no signs of ill health or other physical complications. At 12 week post-trauma these animals displayed marked degeneration of the traumatized joint including synovitis, cartilage erosion, and the formation of peripheral osteophytes. Histological microcracks at the calcified cartilage-subchondral bone interface were also evident in histological sections of these animals. A closed-joint model of traumatic ACL and meniscal rupture was produced, without gross bone fracture, and a pilot, in vivo study showed progressive joint degeneration without any other noticeable physical impairments of the animals over 12 weeks. This closed-joint, traumatic injury model may be useful in future experimental studies of joint disease and various intervention strategies.     

The effects of knee motion and external loading on the length of the anterior cruciate ligament (ACL): a kinematic study

A six-degrees-of-freedom mechanical linkage device was designed and used to study the unconstrained motion of ten intact human cadaver knees. The knees were subjected to externally applied varus and valgus (V-V) moments up to 14 N-m as well as anterior and posterior (A-P) loads up to 100 N. Tests were done at four knee flexion angles; 0, 30, 45, and 90 deg. Significant coupled axial tibial rotation was found, up to 21.0 deg for V-V loading (at 90 deg of flexion) and 14.2 deg for A-P loading (at 45 deg of flexion). Subsequently, the knees were dissected and the locations of the insertion sites to the femur and tibia for the anteromedial (AM), posterolateral (PL), and intermediate (IM) portions of the ACL were identified. The distances between the insertion sites for all external loading conditions were calculated. In the case when the external load was zero, the AM portion of the ACL lengthened with knee flexion, while the PL portion shortened and the intermediate (IM) portion did not change in length. With the application of 14 N-m valgus moment, the PL and IM portions of the ACL lengthened significantly more than the AM portion (p less than 0.001). With the application of 100 N anterior load, the AM portion lengthened slightly less than the PL portion, which lengthened slightly less than the IM portion (p less than 0.005). In general, the amount of lengthening of the three portions of the ACL during valgus and anterior loading was observed to increase with knee flexion angle (p less than 0.001).     

Intercondylar notch width and inner angle of lateral femoral condyle as the risk factors for anterior cruciate ligament injury in female handball players in Herzegovina

The principal purpose of this prospective study was to examine intercondylar notch size and the value of inner angle of lateral femoral condyle as the risk factors for noncontact anterior cruciate ligament ACL injury and than to correlate them to the physical values of the athletes such as body mass index (BMI), hight, wight, etc. There are indentified two type of risk factors, external include shoes-surface interaction, type of playing surface, weather conditions and internal include anatomic, neuromuscular, biomechanical and hormonal factors that may predispose female athlets to noncontact injury of ACL. Among anatomic factors, intercondylar notch stenosis and larger inner angle of lateral condyle of femur as the factors which can cause impigement of ACL, were related to an increased risk of injury of ACL. In this study were included 51 female athlete. In the study group there were 24 female handball players with ACL tear and in control group there were 27 female handball players without any type of injury of the knee, who are practicing handball on a daily basis for at least for two years. In the first step, were gathered clinical data performed by orthopaedic surgeon. In the second step, the femoral notch width and the inner angle of lateral condyle of femur were measured on coronal MR-images. Study has shown that value of inner angle of lateral condyle of femur was significantly higher in athletes with ACL tear compared to those without. Value of width of intercondylar notch was statisticaly smaller in athletes with ACL tear, compared to those without. In the conclusion the inner angle of lateral femoral condyle is better predicting factor for ACL tear in young female handball players compared to intercondylar notch width.     

In vivo calibration of a femoral fixation device transducer for measuring anterior cruciate ligament graft tension: a study in an ovine model

Toward developing a transducer for measuring in vivo tension in anterior cruciate ligament grafts in humans, the objectives of this study were to determine the following: (1) whether the calibration of a previously reported femoral fixation device transducer (FDT) (Ventura et al., 1998) is affected by the presence of the graft when implanted in the tibial metaphysis of an ovine model, (2) whether the FDT remains calibrated at 4 weeks postoperatively, and (3) whether the biological incorporation of the graft occurs prior to a change in the FDT calibration. The FDT was implanted in the hind limb of five sheep using an extra-articular procedure. Both the proximal common digital extensor tendon (i.e., graft) and a Teflon-coated wire were looped around the FDT inside a tunnel in the tibial metaphysis. The FDT was calibrated on three occasions using the loop of wire: once intraoperatively before graft insertion, once intraoperatively after graft insertion, and once postoperatively after the animals had been sacrificed at 4 weeks. Following sacrifice, the load transmitted to the FDT by the graft was also determined. The FDT exhibited linear calibration intraoperatively both before and after graft insertion with an average error relative to the calibration before insertion of the graft of -4.6 percent of full-scale load (150 N) and this average relative error was not significantly different from zero (p = 0.183). After 4 weeks of implantation, the average relative percent error was -5.0 percent and was not significantly different from zero (p = 0.434) indicating that the FDT remained calibrated in the in vivo environment. Because only 15 percent of the graft tension was transmitted to the FDT after 4 weeks, biological incorporation of the graft preceded the loss of calibration. In light of these findings, the FDT offers the capability of measuring the intra-articular ACL graft tension in vivo in animal models and possibly humans before the biological bond develops and also of monitoring the formation and maturation of the biological bond between a graft and bone tunnel.     

The symmetry of the medial collateral and anterior cruciate ligament properties: a biochemical study in the rat hind limb

The medial collateral (MCL) and the anterior cruciate ligament (ACL) of the rat's knee are frequently used in biomedical research and occasionally in ligament healing studies. The contralateral normal ligament serves as a control. In this study the presence of symmetry in the biomechanical properties of the MCL and the ACL was investigated. Bilateral femur-MCL-tibia and femur-ACL-tibia preparations were obtained from the hind limbs of sixty rats and were subjected to tensile testing to failure under the same loading conditions. Tensile load to failure, stiffness and energy absorption capacity were measured and the mode of failure was recorded. All biomechanical parameters were not significantly different between the two knees of the same animal, although significant individual variation was evident. The most common mechanism of failure was mid-substance tear. Symmetry seems to exist in the biomechanical properties of the MCL and the ACL in the rat knee. When ligament healing is evaluated, increased group size is necessary and the use of a normal control group may be advisable. The contralateral normal knee ligament may serve as a control when the properties of an injured ligament are evaluated and when the parameters of tensile testing failure under similar load conditions are applied.     

The effect of anterior cruciate ligament rupture on the timing and amplitude of gastrocnemius muscle activation: a study of alterations in EMG measures and their relationship to knee joint stability

Changes in hamstring and quadriceps activity are well known in individuals with anterior cruciate ligament deficiency (ACLD) to potentially compensate for knee joint instability. However, few studies have explored gastrocnemius activity or its relationship to knee stability. The purpose of this study was therefore to examine the activation characteristics of medial gastrocnemius (MG) in ACLD subjects and relate any changes to knee joint laxity. Two subject cohorts were assessed: those with unilateral ACLD (n=15) and uninjured control subjects (n=11). Surface EMG of the left and right MG were recorded during a controlled single leg hop on each limb. Onset and offset of MG activation relative to take-off, during flight and landing were calculated as well as muscle activity (RMS). Passive antero-posterior knee laxity was measured with a KT1000 arthrometer during a maximal manual displacement test. Medial gastrocnemius activity on the injured side of ACLD participants demonstrated significantly prolonged activation in preparation to hop, minimal muscle inactivity prior to take-off, and increased duration of overall muscle activity when compared to the uninjured side and control subjects (p<0.05). Significant positive correlations were found between passive knee joint laxity and prolonged activation prior to knee bend. RMS of the muscle signal was not significantly different between limbs. Overall, MG on the ACLD side demonstrated longer activation, with minimal rest during the hop test, which may be an attempt to maintain knee stability. Furthermore, the strong relationship between knee laxity and prolonged muscle activation suggests that individuals with a loss of knee stability are more reliant on active control of the gastrocnemius muscle.     

The refractometer index as a correction factor for urinary estradiol in rhesus females

Refractometer indexes were standardized and found to be highly correlated (r = 0.831) to actual creatinine levels. Urinary estradiol corrected by creatinine levels and refractometer indexes were found to be highly correlated (r = 0.857). Predicted ovulation was the same day in 86% of the ovulatory cycles predicted by creatinine and refractometer corrected estradiol levels. Refractometer indexes may be used in place of creatinine levels to correct for urine concentration fluctuations when predicting ovulation in the rhesus female.     

Carcinoembryonic antigen expression level as a predictive factor for response to 5-fluorouracil in colorectal cancer

Carcinoembryonic antigen (CEA) expression has been shown to protect cancer cell lines from apoptosis and anoikis. The aim of this study was to further elucidate the role of CEA expression on resistance to anticancer drugs in human colorectal cancer (CRC). We transfected CEA negative CRC cell line SW742 as well as CHO cells to overexpress CEA and their chemoresistance were assessed by MTT assay. In comparison to the parental cell lines, transfected cells had significantly increased resistance to 5-fluorouracil (5-FU). The results also showed a direct correlation between the amount of cellular CEA protein and 5-FU resistance in CEA expressing cells. We found no significant difference in sensitivity to cisplatin and methotrexate between CEA-transfected cells and their counter parental cells. We also compared the association between CEA expression and chemoresistance of 4 CRC cell lines which differed in the levels of CEA production. The CEA expression levels in monolayer cultures of these cell lines did not correlate with the 5-FU resistance. However, 5-FU treatment resulted in the selection of sub-populations of resistant cells that displayed increased CEA expression levels by increasing drug concentration. We analyzed the effect of 5-FU in a 3D multicellular culture generated from the two CRC cell lines, LS180 and HT29/219. Compared with monolayer culture, CEA production and 5-FU resistance in both cell lines were stimulated by 3D growth. In comparison to the 3D spheroids of parental CHO, we observed a significantly elevated 5-FU resistance in 3D culture of the CEA-expressing CHO transfectants. Our findings suggest that the CEA level may be a suitable biomarker for predicting tumor response to 5-FU-based chemotherapy in CRC.     

Individual and occupational risk factors for knee osteoarthritis: results of a case-control study in Germany

Introduction

A number of occupational risk factors are discussed in relation to the development and progress of knee joint diseases (for example, working in a kneeling or squatting posture, lifting and carrying heavy weights). Besides the occupational factors, a number of individual risk factors are important. The distinction between work-related and other factors is crucial in assessing the risk and in deriving preventive measures in occupational health.

Methods

In a case-control study, patients with and without symptomatic knee osteoarthritis (OA) were questioned by means of a standardised questionnaire complemented by a semi-standardised interview. Controls were matched and assigned to the cases by gender and age. Conditional logistic regression was used in analysing data.

Results

In total, 739 cases and 571 controls were included in the study. In women and men, several individual and occupational predictors for knee OA could be described: obesity (odds ratio (OR) up to 17.65 in women and up to 12.56 in men); kneeling/squatting (women, OR 2.52 (>8,934 hours/life); men, 2.16 (574 to 12,244 hours/life), 2.47 (>12,244 hours/life)); genetic predisposition (women, OR 2.17; men, OR 2.37); and sports with a risk of unapparent trauma (women, OR 2.47 (≥1,440 hours/life); men, 2.58 (≥3,232 hours/life)). In women, malalignment of the knee (OR 11.54), pain in the knee already in childhood (OR 2.08), and the daily lifting and carrying of loads (≥1,088 tons/life, OR 2.13) were related to an increased OR; sitting and smoking led to a reduced OR.

Conclusions

The results support a dose-response relationship between kneeling/squatting and symptomatic knee OA in men and, for the first time, in women. The results concerning general and occupational predictors for knee OA reflect the findings from the literature quite well. Yet occupational risks such as jumping or climbing stairs/ladders, as discussed in the literature, did not correlate with symptomatic knee OA in the present study. With regards to occupational health, prevention measures should focus on the reduction of kneeling activities and the lifting and carrying of loads as well as general risk factors, most notably the reduction of obesity. More intervention studies of the effectiveness of tools and working methods for reducing knee straining activities are needed.     

Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study

Background

The pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated.

Methods

Factors related to the presence of atopy (positive phadiatop) in 1277 mild-to-moderate COPD patients participating in EUROSCOP were analysed using regression analysis. Incidence and remission of respiratory symptoms during 3-year follow-up were analysed using generalised estimating equations models, and association of atopy with lung function decline using linear mixed effects models.

Results

Independent predisposing factors associated with the presence of atopy were: male gender (OR: 2.21; 95% CI: 1.47–3.34), overweight/obese (OR: 1.41; 95% CI: 1.04–1.92) and lower age (OR: 0.98; 95% CI: 0.96–0.99). Atopy was associated with a higher prevalence of cough (OR: 1.71; 95% CI: 1.26–2.34) and phlegm (OR: 1.50; 95% CI: 1.10–2.03), but not with lung function levels or FEV₁ decline. Atopic COPD patients not treated with budesonide had an increased incidence of cough over time (OR: 1.79, 95% CI: 1.03–3.08, p = 0.038), while those treated with budesonide had increased remission of cough (OR: 1.93, 95% CI: 1.11–3.37, p = 0.02) compared to non-atopic COPD patients.

Conclusions

Atopic COPD patients are more likely male, have overweight/obesity and are younger as compared with non-atopic COPD patients. Atopy in COPD is associated with an increased incidence and prevalence of respiratory symptoms. If atopic COPD patients are treated with budesonide, they more often show remission of symptoms compared to non-atopic COPD patients who are treated with budesonide. We recommend including atopy in the diagnostic work-up and management of COPD.     

Mos as a tool for genome-wide insertional mutagenesis in Caenorhabditis elegans: results of a pilot study

The sequence of the Caenorhabditis elegans genome contains approximately 19 000 genes. Available mutants currently exist for <20% of these genes. The existence of a Mos-based inducible transposon system in C.elegans could theoretically serve as a tool to saturate the genome with insertions. We report here the results of a pilot study aimed at assaying this strategy. We generated 914 independent random Mos insertions and determined their location by inverse PCR. The distribution of the insertions throughout the genome does not reveal any gross distortion, with the exception of a major hotspot on chromosome I (rDNA locus). Transposons are evenly distributed between the genic and intergenic regions. Within genes, transposons insert preferentially into the introns. We derived the consensus target site for Mos in C.elegans (ATATAT), which is common to Tc1, another mariner element. Finally, we assayed the mutagenic properties of insertions located in exons by comparing the phenotype of homozygous strains to that of known mutations or RNAi of the same gene. This pilot experiment shows that a Mos-based approach is a viable strategy that can contribute to the constitution of genome-wide collections of identified C.elegans mutants.     

Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls. Eight SNPs showed nominally significant association with BD and were introduced to a meta-analysis of the GWAS and the first follow-up samples. Genetic variation in the neurocan gene (NCAN) showed genome-wide significant association with BD in 2411 patients and 3613 controls (rs1064395, p = 3.02 × 10⁻⁸; odds ratio = 1.31). In a second follow-up step, we replicated this finding in independent samples of BD, totaling 6030 patients and 31,749 controls (p = 2.74 × 10⁻⁴; odds ratio = 1.12). The combined analysis of all study samples yielded a p value of 2.14 × 10⁻⁹ (odds ratio = 1.17). Our results provide evidence that rs1064395 is a common risk factor for BD. NCAN encodes neurocan, an extracellular matrix glycoprotein, which is thought to be involved in cell adhesion and migration. We found that expression in mice is localized within cortical and hippocampal areas. These areas are involved in cognition and emotion regulation and have previously been implicated in BD by neuropsychological, neuroimaging, and postmortem studies.     

Depression as a risk factor for ischaemic heart disease in men: population based case-control study

Objective: To determine the relation between depression, anxiety, and use of antidepressants and the onset of ischaemic heart disease. Design: Population based case-control study. Setting: All 5623 patients registered with one general practice. Subjects: 188 male cases with ischaemic heart disease matched by age to 485 male controls without ischaemic heart disease; 139 female cases with ischaemic heart disease matched by age to 412 female controls. Main outcome measure: Adjusted odds ratios calculated by conditional logistic regression. Results: The risk of ischaemic heart disease was three times higher among men with a recorded diagnosis of depression than among controls of the same age (odds ratio 3.09; 95% confidence interval 1.33 to 7.21; P=0.009). This association persisted when smoking status, diabetes, hypertension, and underprivileged area (UPA(8)) score were included in a multivariate model (adjusted 2.75; 1.13 to 6.69; P=0.03). Men with depression within the preceding 10 years were three times more likely to develop ischaemic heart disease than were the controls (3.13; 1.27 to 7.70; P=0.01). Men with ischaemic heart disease had a higher risk of subsequent ischaemic heart disease than men without ischaemic heart disease (adjusted 2.34; 1.34 to 4.10; P=0.003). Depression was not a risk factor for ischaemic heart disease in women on multivariate analysis (adjusted 1.34; 0.70 to 2.56; P=0.38). Anxiety and subsequent ischaemic heart disease were not significantly associated in men or women. Conclusion: Depression may be an independent risk factor for ischaemic heart disease in men, but not in women.

Key messages

• So far, research into whether depression precedes myocardial infarction has been limited
• This case-control study examined the relation between ischaemic heart disease and depression and the differences in this relation between men and women
• Depression may be a risk factor for ischaemic heart disease in men but not women
• This is independent of diabetes, hypertension, deprivation score, and smoking status