Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells.

A subset of asthma patients suffer from glucocorticoid (GC) insensitivity. T-helper cell type 17 cells have an emerging role in GC insensitivity, although the mechanisms are still poorly understood. We investigated whether interleukin (IL)-17A induces GC insensitivity in airway epithelium by studying its effects on responsiveness of tumour necrosis factor (TNF)-α-induced IL-8 production to budesonide in human bronchial epithelial 16HBE cells. We unravelled the underlying mechanism by the use of specific pathway inhibitors, reporter and overexpression constructs and a histone deacetylase (HDAC) activity assay. We demonstrated that IL-17A-induced IL-8 production is normally sensitive to GCs, while IL-17A pre-treatment significantly reduced the sensitivity of TNF-α-induced IL-8 production to budesonide. IL-17A activated the p38, extracellular signal-related kinase (ERK) and phosphoinositide-3-kinase (PI3K) pathways, and the latter appeared to be involved in IL-17A-induced GC insensitivity. Furthermore, IL-17A reduced HDAC activity, and overexpression of HDAC2 reversed IL-17A-induced GC insensitivity. In contrast, IL-17A did not affect budesonide-induced transcriptional activity of the GC receptor, suggesting that IL-17A does not impair the actions of the ligated GC receptor. In conclusion, we have shown for the first time that IL-17A induces GC insensitivity in airway epithelium, which is probably mediated by PI3K activation and subsequent reduction of HDAC2 activity. Thus, blockade of IL-17A or downstream signalling molecule PI3K may offer new strategies for therapeutic intervention in GC-insensitive asthma.

[Isolated ruptures of the tendon of the biceps femoris muscle]. / Die isolierte Ruptur der Biceps-femoris-Sehne.

Traumatic ruptures of tendons in the region of the knee joint are often accompanied by substantial degenerative and inflammatory alterations, especially when the patella and quadriceps tendons are affected. Isolated ruptures of the tendon of the distal biceps femoris muscle at the dorsolateral aspect of the knee are rare and result in an acute reduction of flexion capability. However, tears of the biceps femoris tendon are not associated with degenerative changes. This article reports on the diagnosis and treatment of a 27-year-old football player who suffered an acute isolated rupture of the biceps femoris tendon.

Mitochondrial dysfunction increases pro-inflammatory cytokine production and impairs repair and corticosteroid responsiveness in lung epithelium.

COPD is characterized by chronic lung inflammation and irreversible lung tissue damage. Inhaled noxious gases, including cigarette smoke, are the major risk factor for COPD. Inhaled smoke first encounters the epithelial lining of the lungs, causing oxidative stress and mitochondrial dysfunction. We investigated whether a mitochondrial defect may contribute to increased lung epithelial pro-inflammatory responses, impaired epithelial repair and reduced corticosteroid sensitivity as observed in COPD. We used wild-type alveolar epithelial cells A549 and mitochondrial DNA-depleted A549 cells (A549 Rho-0) and studied pro-inflammatory responses using (multiplex) ELISA as well as epithelial barrier function and repair (real-time impedance measurements), in the presence and absence of the inhaled corticosteroid budesonide. We observed that A549 Rho-0 cells secrete higher levels of pro-inflammatory cytokines than wild-type A549 cells and display impaired repair upon wounding. Budesonide strongly suppressed the production of neutrophil attractant CXCL8, and promoted epithelial integrity in A549 wild-type cells, while A549 Rho-0 cells displayed reduced corticosteroid sensitivity compared to wild-type cells. The reduced corticosteroid responsiveness may be mediated by glycolytic reprogramming, specifically glycolysis-associated PI3K signaling, as PI3K inhibitor LY294002 restored the sensitivity of CXCL8 secretion to corticosteroids in A549 Rho-0 cells. In conclusion, mitochondrial defects may lead to increased lung epithelial pro-inflammatory responses, reduced epithelial repair and reduced corticosteroid responsiveness in lung epithelium, thus potentially contributing to the pathogenesis of COPD.

How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models.

Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ(0) cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease.

Ultradian rhythms and temporal coherence in sleep EEG in depressed children and adolescents.

BACKGROUND: It has been suggested that a primary ultradian (80-120 minute) rhythm disturbance in EEG underlies sleep abnormalities in adults with depression. The present study evaluated ultradian rhythm disturbances in childhood and adolescent depression. METHODS: Sleep macroarchitecture and temporal coherence in quantitative EEG rhythms were investigated in 50 medication-free outpatients with major depression (25 children and 25 adolescents) and 15 healthy normal controls (5 children and 10 adolescents). RESULTS: Few of the macroarchitectural measures showed significant group effects. In fact, age and sex effects were stronger than disease-dependent components. Temporal coherence of EEG rhythms during sleep did differentiate those with MDD from controls. Both depressed children and adolescents had lower intrahemispheric coherence, whereas interhemispheric was only lower in depressed adolescents in comparison with controls. Gender differences were evident in adolescents, but not children, with MDD with lowest interhemispheric coherence in adolescent girls. CONCLUSIONS: These findings are in keeping with increased risk for depression in females beginning at adolescence and extending throughout adulthood. It was suggested that low temporal coherence in depression reflects a disruption in the fundamental basic rest-activity cycle of arousal and organization in the brain that is strongly influenced by gender.

Delta sleep EEG in depressed adolescent females and healthy controls.

BACKGROUND: Quantitative EEG studies have identified a number of sleep abnormalities in adults with major depressive disorders (MDD), including a reduction in the amplitude of delta activity during NREM sleep. To date, these methodologies have not been used in early onset MDD. METHODS: Delta activity during NREM sleep was compared in eight symptomatic but unmedicated adolescent females with MDD and eight age- and gender-matched healthy controls. RESULTS: The depressed group showed significantly lower delta amplitude and power in the first NREM sleep period. By contrast, standard sleep architecture did not differentiate between groups. LIMITATIONS: Given the sample size, this study is best viewed as tentative. In addition, it has yet to be determined whether adolescent males with MDD also show delta sleep abnormalities. Further, failure to find between-group differences in REM latency or other macroarchitectural measures may be due to the small sample size. CONCLUSIONS: The findings of this study underscore the utility of quantitative sleep EEG techniques in early onset MDD. The results of the present study do, however, diverge from reports in adults with MDD, where delta abnormalities are more prevalent in men. Such findings suggest that the maturational time course of sleep EEG disturbances may differ for males and females with depression. Early emergence of delta abnormalities in depression may be of relevance to clinical course of illness.

Bisegmental rotational fracture dislocation of the pediatric cervical spine. A case report.

STUDY DESIGN: A case of a bisegmental rotational fracture dislocation in the pediatric cervical spine is presented. OBJECTIVES: To highlight the problems in the diagnostics and surgical management of this rare type of injury. SUMMARY OF BACKGROUND DATA: Fractures of the cervical spine are relatively uncommon in childhood. To the authors' knowledge, this is the first reported case of a bisegmental rotational fracture dislocation in the pediatric cervical spine managed by a combined anteroposterior approach. METHODS: A 6-year-old girl was hit by a car as a pedestrian. In addition to an open fracture dislocation of the Lisfranc joint in the right foot, she sustained a bisegmental fracture dislocation at the lower cervical spine (C3-C5) with no neurologic deficit. The complete diagnosis of a locked rotational fracture dislocation could be established only by using computed tomography scans with three-dimensional reconstructions. The injury was managed with a combined anteroposterior open reduction and a bisegmental anterior fusion. RESULTS: Implant removal was performed after bony fusion 6 months after surgery. At follow-up assessment 2.5 years later, the girl had a good radiologic result and a full and pain-free functional recovery. CONCLUSIONS: Bisegmental rotational fracture dislocations in pediatric cervical spines are not easily diagnosed and may require three-dimensional computed tomography scan reconstructions for complete assessment. In such rare cases, a combined anteroposterior surgical procedure may be indicated, with a bisegmental anterior fusion providing a good functional result.

The influence of screw geometry on hamstring tendon interference fit fixation.

We used a standardized model of calf tibial bone to investigate the influence of screw diameter and length on interference fit fixation of a three-stranded semitendinosus tendon graft for anterior cruciate ligament reconstruction. Biodegradable poly-(L-lactide) interference screws with a diameter of 7, 8, and 9 mm and a length of 23 and 28 mm were used. We examined results in three groups of 10 specimens each: group 1, screw diameter equaled graft diameter and screw length was 23 mm; group 2, screw diameter equaled graft diameter plus 1 mm and screw length was 23 mm; group 3, screw diameter equaled graft diameter and screw length was 28 mm. The mean pull-out forces in groups 1, 2, and 3 were 367.2+/-78 N, 479.1+/-111.1 N, and 537.4+/-139.1 N, respectively. The force data from groups 2 and 3 were significantly higher than those from group 1. These results indicate that screw geometry has a significant influence on hamstring tendon interference fit fixation. Increasing screw length improves fixation strength more than oversizing the screw diameter. This is important, especially for increasing tibial fixation strength because the tibial graft fixation site has been considered to be the weak link of such a reconstruction.

Biodegradable interference screw fixation exhibits pull-out force and stiffness similar to titanium screws.

Recently, increased interest in biodegradable interference screws for bone-tendon-bone graft fixation has led to numerous screws becoming available. The implants are made from different polymers and have different designs, which might influence their mechanical properties. Several studies have reported a wide range of mechanical results for these screws using different biomechanical models. The aim of the present study is to compare reliable biomechanical data for six different biodegradable interference screws, consisting of five different polymers, with a conventional titanium screw in a standardized model. Seventy proximal calf tibias were used to determine maximal pull-out force, stiffness of fixation, and insertion torque for interference screw fixation of bone-tendon-bone grafts. Additionally, maximal torque at failure was determined. Data were analyzed with respect to aspects of screw design, such as drive and thread shape. Five of the six biodegradable screws provided initial pull-out force and stiffness of fixation comparable with that of a conventional titanium screw. Torque at failure can be greatly increased by adapting the drive design to the mechanical properties of the polymeric raw material. A correlation between pull-out force and thread height indicates that fixation rigidity depends on screw design, even in a biodegradable implant.

Developmental changes in human infant visual-evoked potentials to patterned stimuli recorded at different scalp locations.

Visual-evoked potentials (VEPs) to patterned stimuli were recorded from 4 different scalp locations in 2 groups of infant subjects (ages 6 weeks and 10 weeks). Seven VEP components were identified that changed in amplitude as a function of changes in the amount of contour in the stimuli presented. Developmental shifts in these effects were interpreted to indicate a change in the physiological locus of control of infant visual preferences from a subcortical to a cortical locus over the age range examined.

The electrophysiological correlates of dream recall and nonrecall from stage 2 sleep.

This research examined the relationship between cortical activation, defined by electroencephalographic (EEG) measures, and the ability to recall dreams following awakenings from Stage 2 sleep. Period-analyzed EEG data from 40 subjects were examined for the preawakening, postawakening, and preawakening-to-postawakening time intervals. Recall differed from nonrecall at the postawakening and preawakening-to-postawakening periods on measures of muscle activity and time spent in the sigma (12-16 Hz) frequency band. There were no distinctions in recall ability on EEG hemispheric asymmetry measures. Generally, the findings do not support the hypothesis linking increased recall ability to increases in cortical activation prior to awakening. However, the recall groups depicted a different pattern of arousal in their transition from sleep to wakefulness.

A multivariate comparison between two EEG analysis techniques: period analysis and fast Fourier transform.

The present study investigated the statistical correspondence between two frequently used methods of analysing tonic EEG activity: (1) period analysis and (2) Fast Fourier Transforms (FFTs). For replication purposes, independent statistical analyses were carried out on the EEG of sleeping subjects and of awake subjects performing a cognitive task. From the results of two canonical correlations, the first two canonical variates were sufficient to account for 97% (awake group) and 99% (sleeping group) of the variance between the separate linear composites of all FFT and period analysis variables. Linear regressions of the 3 dependent measures generated by period analysis onto each respective FFT measure gave high and significant multiple correlations for all frequencies. Zero-order correlations were also gathered and discussed. It is concluded that period analytic and FFT analysed EEG share similar types of information and that period analysis can be used more often in EEG research.

Biological rhythm disturbance in depression: temporal coherence of ultradian sleep EEG rhythms.

BACKGROUND: Recent studies have suggested that major depressive disorders are associated with a breakdown in the organization of ultradian rhythm in sleep EEG. The present study used cross-spectral analysis of sleep EEG to confirm this finding, in a larger-scale study, evaluating the influence of gender and age on ultradian rhythms in depression. METHODS: Temporal coherence of ultradian (80-120 min) rhythms in beta, theta and delta, recorded from central and parietal sites, were compared in 120 symptomatic, unmedicated, depressed outpatients and 59 healthy normal controls. RESULTS: Few macro-architectural differences were noted between patients and controls. However, interhemispheric beta and theta coherence and intrahemispheric coherence between beta and delta rhythms were significantly lower in depressed patients. Coherence measures were lowest in women with depression and highest in men in the control group, but were not strongly influenced by age. Over 65% of depressed patients were > or = 2 standard deviations below normal on at least one coherence measure, in sharp contrast to less than 10% of patients on macro-architectural variables. CONCLUSIONS: It was concluded that dysregulation of ultradian rhythms characterizes the majority of depressed out-patients, primarily women, even when macro-architecture did not differentiate groups. The outcome of this study supports the view that the pathophysiology of depression is strongly influenced by gender. It was suggested that low temporal coherence in depression reflects a breakdown in the organization of sleep EEG rhythms within and between the two hemispheres.

The management of polytraumatized patients in Germany.

Polytrauma care in Germany is well organized and follows clear-cut demands: (1) to reduce the therapy-free interval, (2) to ensure qualified and sufficient preclinical treatment, (3) to minimize transportation time, and (4) to immediately transport the patient to an adequate level trauma center. These concepts include wide use of rescue helicopters that are based in 51 stations and cover the entire country. In addition, there is a countrywide system of emergency physician ambulances. All rescue forces are coordinated by special rescue coordination centers to ensure maximum efficacy. Specially trained emergency physicians are taken to the scenes of accidents in the helicopters or emergency physician ambulances and provide aggressive and advanced shock and trauma treatment at the scene. The patients then are carried to high level trauma centers by air transport. In the trauma centers, standardized diagnostic and treatment protocols are applied by trauma surgery teams who care for the entire trauma, including orthopaedic trauma. In addition to stopping mass bleeding, basic concepts include aggressive infusion shock therapy, early machine oxygenation, and instant stabilization of all open, all major pelvic, and all lower limb long bone fractures. These management concepts have decreased the lethality numbers in polytrauma from 40% in 1972 to 18% in 1991. Most polytrauma survivors can be rehabilitated socially to an excellent to acceptable degree.

Changes in direct current potentials during sleep deprivation.

Previous research reported changes in steady-state brain electrical activity during sleep. However, due to the quasi-linear nature of the Direct Current (DC) changes, artifact contamination was a potential confound. The present study was performed to further explore DC potentials and to help establish its validity. Twenty-five male university students (13 control and 12 sleep-deprived; mean age 19 y (range 17-27 y) served as subjects. During wakefulness, subjects were tested every hour while standard EEG activity recordings were made, as well as DC measurement. Split plot analyses of variance (ANOVAs) revealed that changes in DC activity levels differed between the two groups. The control subjects showed the same pattern of decreasing DC observed previously with a return to baseline levels during waking hours. The sleep-deprived subjects showed a smaller decrease in DC level through the night, followed by a rise in DC level that continued until the end of the 24 h study. It was concluded that DC measurement reflects changes in brain state associated with fatigue that are not attributable to artifactual processes.

Biodegradable implants in sports medicine: the biological base.

Biodegradable implants are increasingly used in the field of operative sports medicine. Today, a tremendous variety of implants such as interference screws, staples, sutures, tacks, suture anchors, and devices for meniscal repair are available. These implants consist of different biodegradable polymers that have substantially different raw material characteristics such as in vivo degradation, host-tissue response, and osseous replacement. Because these devices have become the standard implant for several operative procedures, it is essential to understand their biological base. The purpose of this report is to provide a comprehensive insight into biodegradable implant biology for a better understanding of the advantages and risks associated with using these implants in the field of operative sports medicine. In particular, in vivo degradation, biocompatibility, and the osseous replacement of the implants are discussed. A standardized classification system to document and treat possible adverse tissue reactions is given, with special regard to extra-articular and intra-articular soft-tissue response and to osteolytic lesions.

Initial fixation strength of modified patellar tendon grafts for anatomic fixation in anterior cruciate ligament reconstruction.

Recently it has been shown that anatomic tibial graft fixation in anterior cruciate ligament (ACL) reconstruction is preferable in order to increase isometry and knee stability. To facilitate anatomic patellar tendon graft fixation, customized graft length shortening is necessary. The purpose of this study was to compare the initial fixation strength of four different shortened patellar tendon grafts including three bone plug flip techniques and direct patellar tendon-to-bone interference fit fixation in a model with standardized bone density. Ninety calf tibial plateaus (22 to 24 weeks old) with adjacent patella and extensor ligaments were used. Tendon grafts were shortened by flipping the bone plug over the tendon leaving a tendon-tendon-bone (TTB) construct and, as the first modification in the opposite direction resulting in a tendon-bone-tendon (TBT) construct. The second modification consisted of the TBT construct with interference screw position at the lateral aspect of the bone plug (TBTlat). As the fourth modification the tendon graft was directly fixed (Tdirect) with an interference screw. In addition, a round-threaded titanium (RCI; Smith & Nephew DonJoy, Carlsbad, CA), a round-threaded biodegradable screw (Sysorb; Sulzer Orthopedics, Münsingen, Switzerland), and a conventional titanium interference screw (Arthrex Inc, Naples, FL) were compared. We found that TTB (mean 441 N for biodegradable screw, 357 N for RCI screw, 384 N for conventional screw) and TBT (mean 407 N for biodegradable screw, 204 N for RCI screw, 392 N for conventional screw) construct fixation achieves comparable fixation strength, although failure in the TTB was due to tendon strip off at its ligamentous insertion. The highest failure load was found in TBTlat fixation (mean 610 N for biodegradable screw, 479 N for RCI screw). Therefore, this technique should be recommended when using a tendon flip technique. The failure load for Tdirect fixation (mean 437 N for biodegradable screw, 364 N for RCI screw) was similar to that of TTB and TBT fixation, which may indicate that a patellar-tendon graft harvested without its patellar bone plug and directly fixed with an interference screw is equivalent to a flipped graft. This may additionally reduce harvest site morbidity and eliminates the risk of patellar fracture. The fixation strength of round-threaded biodegradable and conventional titanium interference screws was similar, whereas that of round-threaded titanium screws was significantly lower in the patellar tendon flip-techniques. However, it should be taken into consideration that round-threaded titanium screws are proposed for direct tendon-to-bone fixation.

[Replacement of the anterior cruciate ligament. Biomechanical studies for patellar and semitendinosus tendon fixation with a poly(D,L-lactide) interference screw]. / Ersatz des vorderen Kreuzbands. Biomechanische Untersuchungen zur Patellar- und Semitendinosussehnenverankerung mit einer Poly (D,L-Laktid)-Interferenzschraube.

Anterior cruciate ligament (ACL) reconstruction using autologous hamstring tendons are being performed more frequently and satisfactory results have been reported. Advantages such as low donor site morbidity and ease of harvest as well as disadvantages like low initial construct stiffness have been described. Recently, it has been demonstrated that graft fixation close to the original ACL insertion sites increases anterior knee stability and graft isometry. Hamstring tendon fixation techniques using interference screws offer this possibility. To reduce the risk of graft laceration, a round threaded titanium interference screw (RCI) was developed. To improve initial fixation strength, fixation techniques for hamstring tendons with separate or attached tibial bone plugs were introduced. However, data on fixation strength do not yet exist. With respect to the proposed advantages of biodegradable implants, like undistorted magnetic resonance imaging, uncompromised revision surgery and a decreased potential of graft laceration during screw insertion, we performed pullout tests of round threaded biodegradable and round threaded titanium interference screw fixation of semitendinosus (ST) grafts with and without distally attached tibial bone plugs. Data were compared with bone-tendon-bone (BTB) graft fixation using biodegradable and conventional titanium interference screws. We used 56 proximal calf tibiae to compare maximum pullout force, screw insertion torque, and stiffness of fixation for biodegradable direct ST tendon and bone plug fixation (group I: without bone plug, group II: with bone plug) versus titanium interference screw fixation (group III: without bone plug, group IV: with bone plug). A round threaded biodegradable poly-(D, L-lactide) (Sysorb) and a round threaded titanium interference screw (RCI) were used. As a control calf bone-tendon-bone (BTB) grafts fixed with either poly-(D, L-lactide) (group V) or conventional titanium (group VI) interference screws were used. ST tendons were harvested either with or without their distally attached tibial bone plugs from human cadavers and were folded to a three-stranded graft. Specimen were loaded in a material testing machine with the applied load parallel to the long axis of the bone tunnel. Maximum pullout force of ST bone plug (group III: 717 N +/- 90, group IV: 602 N +/- 117) fixation was significantly higher than that of direct tendon (group I: 507 N +/- 93, group III: 419 N +/- 77) fixation. Maximum pullout force of biodegradable screw ST fixation was higher than that of titanium screw fixation in both settings. There was no significant difference in pullout force between biodegradable (713 N +/- 210) and titanium (822 N +/- 130) BTB graft fixation or between ST fixation with bone plug and biodegradable screw with BTB fixation. Pullout force of hamstring tendon interference screw fixation can be improved by using a biodegradable implant. In addition, initial pullout force can be greatly improved by harvesting the hamstring tendon graft with its distally attached tibial bone plug. This may be important, especially in improving tibial graft fixation. This study encourages further research in tendon-bone healing with direct interference screw fixation to confirm the potential of this advanced method.

Conceptual and methodological considerations towards the development of computer-controlled research on the electro-physiology of sleep.

A critical discussion of the visual scoring approach to the measurement of sleep electrophysiology details some theoretical shortcomings of that procedural model. An alternative approach employing high-speed, general purpose digital computers is then presented. It is argued that the measurement potential of computers is barely tapped by using computers to score sleep stages and the advantages of collecting data which are suitable for parametric and multivariate statistical analysis are described. Researchers are urged to include detailed reports on their procedural choices along with a discussion of the methodological implications of these procedures. Examples of computer collected data are presented along with a description of some simple data reduction strategies.

Hamstring tendon fixation using interference screws: a biomechanical study in calf tibial bone.

It has recently been shown that graft fixation close to the ACL insertion site is optimal in order to increase anterior knee stability. Hamstring tendon fixation using interference screws offers this possibility and a round threaded titanium interference screw has been previously developed. The use of a round threaded biodegradable interference screw may be equivalent. In addition, to increase initial fixation strength, graft harvest with a distally attached bone plug may be advantageous, but biomechanical data do not exist. This study compares the initial pullout force, stiffness of fixation, and failure modes of three strand semitendinosus grafts in 36 proximal calf tibiae using either biodegradable poly-(D,L-lactide) (Sysorb; Sulzer Orthopaedics Ltd, Münsingen, Switzerland) or round threaded titanium (RCI; Smith & Nephew DonJoy, Carlsbad, CA) interference screws, harvested either without (biodegradable: group I, titanium III) or with (biodegradable: group II, titanium: group IV) attached tibial bone plugs. Maximum pullout force in group I (507 +/- 93 N) was significantly higher than in group III (419 +/- 77 N). Pullout force of bone plug fixation was significantly higher than that of direct tendon fixation (717 +/- 90 N in group II and 602 +/- 117 N in group IV). Pullout force of biodegradable fixation was significantly higher in both settings. These results indicate that initial pullout force of hamstring-tendon graft interference screw fixation can be increased by using a biodegradable interference screw. In addition, initial pullout force of hamstring-tendon graft fixation with an interference screw can be greatly increased by harvesting the graft with its distally attached tibial bone plug.