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1.
Nature ; 566(7744): 403-406, 2019 02.
Article in English | MEDLINE | ID: mdl-30728499

ABSTRACT

Most tumours have an aberrantly activated lipid metabolism1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.


Subject(s)
Fatty Acids/chemistry , Fatty Acids/metabolism , Metabolic Networks and Pathways , Neoplasms/metabolism , Neoplasms/pathology , Animals , Cell Line, Tumor , Cell Membrane/metabolism , Cell Proliferation , Fatty Acid Desaturases/metabolism , Female , HEK293 Cells , Humans , Male , Mice , Oleic Acids/metabolism , Palmitates/metabolism , Palmitic Acids/metabolism , Stearoyl-CoA Desaturase/metabolism
2.
Acta Oncol ; 63: 542-551, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967220

ABSTRACT

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers. Using the Auria Biobank in Finland, we aimed to identify and characterize patients with these gene fusions, and describe their clinical and tumor characteristics, treatments received, and outcomes. MATERIAL AND METHODS: We evaluated pediatrics with any solid tumor type and adults with colorectal cancer (CRC), non-small cell lung cancer (NSCLC), sarcoma, or salivary gland cancer. We determined tropomyosin receptor kinase (TRK) protein expression by pan-TRK immunohistochemistry (IHC) staining of tumor samples from the Auria Biobank, scored by a certified pathologist. NTRK gene fusion was confirmed by next generation sequencing (NGS). All 2,059 patients were followed-up starting 1 year before their cancer diagnosis. RESULTS: Frequency of NTRK gene fusion tumors was 3.1% (4/127) in pediatrics, 0.7% (8/1,151) for CRC, 0.3% (1/288) for NSCLC, 0.9% (1/114) for salivary gland cancer, and 0% (0/379) for sarcoma. Among pediatrics there was one case each of fibrosarcoma (TPM3::NTRK1), Ewing's sarcoma (LPPR1::NTRK2), primitive neuroectodermal tumor (DAB2IP::NTRK2), and papillary thyroid carcinoma (RAD51B::NTRK3). Among CRC patients, six harbored tumors with NTRK1 fusions (three fused with TPM3), one harbored a NTRK3::GABRG1 fusion, and the other a NTRK2::FXN/LPPR1 fusion. Microsatellite instability was higher in CRC patients with NTRK gene fusion tumors versus wild-type tumors (50.0% vs. 4.4%). Other detected fusions were SGCZ::NTRK3 (NSCLC) and ETV6::NTRK3 (salivary gland cancer). Four patients (three CRC, one NSCLC) received chemotherapy; one patient (with CRC) received radiotherapy. CONCLUSION: NTRK gene fusions are rare in adult CRC, NSCLC, salivary tumors, sarcoma, and pediatric solid tumors.


Subject(s)
Receptor, trkA , Receptor, trkC , Humans , Finland/epidemiology , Male , Child , Female , Adult , Middle Aged , Adolescent , Receptor, trkA/genetics , Child, Preschool , Young Adult , Receptor, trkC/genetics , Aged , Biological Specimen Banks , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Fusion , Sarcoma/genetics , Sarcoma/pathology , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/pathology , Receptor, trkB/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Infant , Oncogene Proteins, Fusion/genetics , Neoplasms/genetics , Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , High-Throughput Nucleotide Sequencing , Membrane Glycoproteins
3.
Eur J Appl Physiol ; 116(9): 1807-17, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27448605

ABSTRACT

PURPOSE: The aim of this study was to describe thigh muscle activation during cycling using intramuscular electromyographic recordings of eight thigh muscles, including the biceps femoris short head (BFS) and the vastus intermedius (Vint). METHODS: Nine experienced cyclists performed an incremental test (start at 170Ā W and increased by 20Ā W every 2Ā min) on a bicycle ergometer either for a maximum of 20Ā min or to fatigue. Intramuscular electromyography (EMG) of eight muscles and kinematic data of the right lower limb were recorded during the last 20Ā s in the second workload (190Ā W). EMG data were normalized to the peak activity occurring during this workload. Statistical significance was assumed at pĀ ≤Ā 0.05. RESULTS: The vastii showed a greater activation during the 1st quadrant compared to other quadrants. The rectus femoris (RF) showed a similar activation, but with two bursts in the 1st and 4th quadrants in three subjects. This behavior may be explained by the bi-articular function during the cycling movement. Both the BFS and Vint were activated longer than, but in synergy with their respective agonistic superficial muscles. CONCLUSION: Intramuscular EMG was used to verify muscle activation during cycling. The activation pattern of deep muscles (Vint and BFS) could, therefore, be described and compared to that of the more superficial muscles. The complex coordination of quadriceps and hamstring muscles during cycling was described in detail.


Subject(s)
Bicycling/physiology , Electromyography/methods , Hamstring Muscles/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Quadriceps Muscle/physiology , Adult , Female , Humans , Knee Joint/physiology , Male , Reproducibility of Results , Sensitivity and Specificity
4.
Gynecol Endocrinol ; 30(1): 38-41, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24219598

ABSTRACT

Endometriosis compromises the quality of life of countless women worldwide and is a leading cause of disability. Clinical symptoms of endometriosis can be very heterogeneous leading to a long interval between onset of symptoms and surgical diagnosis. A noninvasive, rapid diagnostic test is urgently needed. In this prospective study, we evaluated the usefulness of Cytokeratin-19 (CK19) as a biomarker for the diagnosis of endometriosis through urine and serum ELISA. 76 reproductive-aged women undergoing laparoscopy for benign conditions were included to this study and divided into two groups by the presence (n = 44) or absence (n = 32) of endometriosis. There was no statistically significant correlation between the concentration of CK19 in urine (p = 0.51) or in serum (p = 0.77) and the diagnosis of endometriosis. Assigning the samples to the proliferative or secretory cycle stage did not sufficiently lower the p values. In this study, the promising data reported in the recent literature about CK19 serving as a sufficient biomarker for endometriosis could not be verified when tested in a larger sample size. Further studies are warranted to explore the usefulness of CK19 in the diagnosis of endometriosis.


Subject(s)
Biomarkers/blood , Biomarkers/urine , Endometriosis/diagnosis , Keratin-19/blood , Keratin-19/urine , Peritoneal Diseases/diagnosis , Adult , Case-Control Studies , Endometriosis/blood , Endometriosis/urine , Female , Humans , Laparoscopy , Menstrual Cycle/blood , Menstrual Cycle/urine , Peritoneal Diseases/blood , Peritoneal Diseases/urine
5.
HNO ; 62(11): 813-7, 2014 Nov.
Article in German | MEDLINE | ID: mdl-25312591

ABSTRACT

INTRODUCTION: Hamartomas are benign tumor-like lesions resulting from incorrectly differentiated germplasm and can manifest in different organ systems. In the nasal cavity and the sinuses these lesions are rare. Only few data on etiology, epidemiology and clinical significance of these tumors exist to date. MATERIALS AND METHODS: In a retrospective study, material from patients treated in the Clinic for Otorhinolaryngology, Head and Neck Surgery of the Ulm Military Hospital was screened on the incidence and clinical courses of respiratory epithelial adenomatoid hamartomas (REAH) of the nose and nasal cavity. Furthermore, for cases of REAH, formalin-fixated paraffin-embedded tissue samples were re-evaluated and examined for human papillomavirus (HPV) DNA by PCR. RESULTS: Tissue samples from 8145Ā surgical interventions on the nose and nasal sinuses fromĀ 2003 toĀ 2012 were included. A total of 22Ā patients (3Ā female, 19Ā male; median age 57.5Ā years) diagnosed with REAH could be identified. Major complaints were nasal blockage (91 %), sinusitis (82 %), rhinorrhea (36 %) and cephalgia (23 %). Nasal endoscopy showed polyps in 68 % of patients. Native nasal sinus CT scans revealed no indications of REAH. Intraoperatively, hamartomas were found in 12Ā patients originating from the ethmoid bone, in 8Ā from the middle meatus or infundibulum and in 2Ā from the olfactory cleft. Macroscopic and histological examination showed compact lesions sized between 4Ā and 25Ā mm in the largest diameter containing homologous tissue, without signs of dysplasia or malignancy. HPV DNA was not identified in any case. CONCLUSION: REAH of the nasal cavity and sinuses are rare benign local tissue lesions, usually without any autonomous proliferation. Clinical signs and findings correspond to those in polypoid pansinusitis. Only with single-sided or olfactory cleft location might CT scans provide indication of a tumorous lesion. For differentiation from true neoplasms, surgical resection and histopathological clarification is indicated. On the basis of current knowledge, complete surgical resection is adequate therapy.


Subject(s)
Adenomatoid Tumor/pathology , Hamartoma/pathology , Nasal Polyps/pathology , Nose Neoplasms/pathology , Adult , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Rare Diseases/pathology , Reproducibility of Results , Sensitivity and Specificity
6.
Oncotarget ; 15: 106-116, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38329731

ABSTRACT

Selective tropomyosin receptor kinase (TRK) inhibitors are approved targeted therapies for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. Country-specific estimates of NTRK gene fusion frequency, and knowledge on the characteristics of affected patients, are limited. We identified patients with histologically-confirmed papillary thyroid cancer (PTC) from Finland's Auria Biobank. TRK protein expression was determined by pan-TRK immunohistochemistry. Immuno-stained tumor samples were scored by a certified pathologist. Gene fusions and other co-occurring gene alterations were identified by next generation sequencing. Patient characteristics and vital status were determined from linked hospital electronic health records (EHRs). Patients were followed from 1 year before PTC diagnosis until death. 6/389 (1.5%) PTC patients had an NTRK gene fusion (all NTRK3); mean age 43.8 years (and none had comorbidities) at PTC diagnosis. Gene fusion partners were EML4 (n = 3), ETV6 (n = 2), and RBPMS (n = 1). Of 3/6 patients with complete EHRs, all received radioactive iodine ablation only and were alive at end of follow-up (median observation, 9.12 years). In conclusion, NTRK gene fusion is infrequent in patients with PTC. Linkage of biobank samples to EHRs is feasible in describing the characteristics and outcomes of patients with PTC and potentially other cancer types.


Subject(s)
Biological Specimen Banks , Receptors, Amino Acid , Thyroid Neoplasms , Humans , Adult , Thyroid Cancer, Papillary/genetics , Finland , Iodine Radioisotopes , Thyroid Neoplasms/genetics , Gene Fusion
7.
Int J Sports Med ; 34(2): 176-82, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22972247

ABSTRACT

This study aimed to evaluate biomechanics during seated double-poling exercises in individuals with spinal cord injury (SCI) and to compare these with those of able-bodied persons (AB). 26 participants volunteered for the study; 13 with SCI (injury levels C7-T12), and 13 AB. A seated double-poling ergometer (SDPE) was developed. 3-dimensional kinematics was measured and piezoelectric force sensors were used to register force in both poles for calculation of power during incremental intensities. Significantly lower power outputs, (143.2 Ā± 51.1 vs. 198.3 Ā± 74.9 W) and pole forces (137.1 Ā± 43.1 vs. 238.2 Ā± 81.2 N) were observed during maximal effort in SCI compared to AB. Sagittal upper trunk range of motion increased with intensity and ranged from 6.1-34.8Ā° for SCI, and 6.9-31.3Ā° for AB, with larger peak amplitudes in flexion for AB (31.4 Ā± 12.9Ā°) compared to SCI (10.0 Ā± 8.0Ā°). All subjects with SCI were able to exercise on the SDPE. Upper body kinematics, power and force outputs increased with intensity in both groups, but were in general, lower in SCI. In conclusion, the SDPE could be successfully used at low to high work intensities enabling both endurance and strength training for individuals with SCI.


Subject(s)
Ergometry/instrumentation , Exercise Therapy/instrumentation , Spinal Cord Injuries/therapy , Upper Extremity/physiology , Adult , Aged , Biomechanical Phenomena , Case-Control Studies , Cervical Vertebrae , Exercise Therapy/standards , Female , Humans , Male , Middle Aged , Movement , Physical Exertion , Range of Motion, Articular , Shoulder Joint/physiology , Spinal Cord Injuries/physiopathology , Thoracic Vertebrae
8.
ESMO Open ; 8(5): 101628, 2023 10.
Article in English | MEDLINE | ID: mdl-37713929

ABSTRACT

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 andĀ 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Laboratories , Retrospective Studies , Pandemics , Mutation , ErbB Receptors/genetics , Europe
9.
Cancer Treat Res Commun ; 33: 100623, 2022.
Article in English | MEDLINE | ID: mdl-36041373

ABSTRACT

INTRODUCTION: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. Limited data exist on the overall survival (OS) of patients with tumors with NTRK gene fusions and on the co-occurrence of NTRK fusions with other oncogenic drivers. MATERIALS AND METHODS: This retrospective study included patients enrolled in the Genomics England 100,000 Genomes Project who had linked clinical data from UK databases. Patients who had undergone tumor whole genome sequencing between March 2016 and July 2019 were included. Patients with and without NTRK fusions were matched. OS was analyzed along with oncogenic alterations in ALK, BRAF, EGFR, ERBB2, KRAS, and ROS1, and tumor mutation burden (TMB) and microsatellite instability (MSI). RESULTS: Of 15,223 patients analyzed, 38 (0.25%) had NTRK gene fusions in 11 tumor types, the most common were breast cancer, colorectal cancer (CRC), and sarcoma. Median OS was not reached in both the NTRK gene fusion-positive and -negative groups (hazard ratio 1.47, 95% CI 0.39-5.57, PĀ =Ā 0.572). A KRAS mutation was identified in two (5%) patients with NTRK gene fusions, and both had hepatobiliary cancer. High TMB and MSI were both more common in patients with NTRK gene fusions, due to the CRC subset. While there was a higher risk of death in patients with NTRK gene fusions compared to those without, the difference was not statistically significant. CONCLUSION: This study supports the hypothesis that NTRK gene fusions are primary oncogenic drivers and the co-occurrence of NTRK gene fusions with other oncogenic alterations is rare.


Subject(s)
Neoplasms , Receptor, trkA , Humans , Receptor, trkA/genetics , Protein-Tyrosine Kinases/genetics , Retrospective Studies , Proto-Oncogene Proteins/genetics , Neoplasms/genetics
10.
Cancer Treat Res Commun ; 25: 100260, 2020.
Article in English | MEDLINE | ID: mdl-33310366

ABSTRACT

OBJECTIVES: We aimed to describe mesothelin (MSLN) and programmed cell death 1 ligand 1 (PD-L1) tumour overexpression amongst patients with malignant mesothelioma (MM), and their associations with survival, amongst a cohort of patients with MM in Finland. METHODS: Between 2004 and 2017, 91 adults with histologically confirmed MM were identified from the Auria Biobank in Finland and followed-up using linked data from electronic health records and national statistics. Biomarker content in tumour cell membranes was determined using automated Immunohistochemistry on histological sections. Stained tumour sections were scored for MSLN and PD-L1 intensity. Adjusted associations between MSLN/PD-L1 co-expression and mortality were evaluated by estimating hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression. RESULTS: Biomarker overexpression occurred in 52 patients for MSLN and 34 patients for PD-L1 and was associated with tumour histology and certain comorbidities. Fifteen per cent of patients had a tumour that overexpressed both biomarkers; r =-0.244, p-value: 0.02. Compared with MSLN+/PD-L1+ patients, HRs (95% CIs) for death were 4.18 (1.71-10.23) for MSLN-/PD-L1+ patients, 3.03 (1.35-6.77) for MSLN-/PD-L1- patients, and 2.13 (0.97-4.67) for MSLN+/PD-L1- patients. CONCLUSIONS: Both MSLN and PD-L1 markers were independent prognostic indicators in patients with MM. Overexpression of MSLN was associated with longer survival; yet their combined expression gave a better indication of survival. The risk of death was four times higher amongst MSLN-/PD-L1+ patients than in MSLN+/PD-L1+ patients.


Subject(s)
Antigens, Neoplasm/therapeutic use , B7-H1 Antigen/metabolism , GPI-Linked Proteins/therapeutic use , Mesothelioma, Malignant/drug therapy , Aged , Aged, 80 and over , Antigens, Neoplasm/pharmacology , Cohort Studies , Female , Finland , GPI-Linked Proteins/pharmacology , Humans , Male , Mesothelin , Prognosis
11.
Head Neck ; 42(4): 625-635, 2020 04.
Article in English | MEDLINE | ID: mdl-31919967

ABSTRACT

BACKGROUND: MET has emerged as target in head and neck squamous cell carcinoma (HNSCC). However, clinical data on MET inhibition in HNSCC are limited. METHODS: HNSCC biopsies and cell lines were tested for MET activity. The response of cell lines to BAY-853474 was tested in proliferation assays. The prognostic value of MET expression was also analyzed. RESULTS: HNSCC cell lines do not respond to MET inhibition. MET-dependent gastric cancer cell lines have much higher levels of MET expression and phosphorylation than HNSCC cell lines. Clinical samples of HNSCC contain much less MET than responsive models. CONCLUSIONS: No clinical response to MET inhibitors in monotherapy may be expected in unselected cases of HNSCC. Only selected patients with MET amplifications should be treated with MET inhibitors. Patients with increased MET immunoreactivity have shorter overall survival. MET might be useful as marker for the detection of patients with more aggressive types of HNSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Humans , Proto-Oncogene Proteins c-met/genetics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/genetics
12.
Cancers (Basel) ; 12(2)2020 Feb 12.
Article in English | MEDLINE | ID: mdl-32059441

ABSTRACT

Evidence has accumulated asserting the importance of cullin-RING (really interesting new gene) ubiquitin ligases (CRLs) and their regulator Cullin-associated neural-precursor-cell-expressed developmentally down-regulated 8 (NEDD8) dissociated protein 1 (Cand1) in various cancer entities. However, the role of Cand1 in prostate cancer (PCa) has not been intensively investigated so far. Thus, in the present study, we aimed to assess the relevance of Cand1 in the clinical and preclinical setting. Immunohistochemical analyses of radical prostatectomy specimens of PCa patients showed that Cand1 protein levels are elevated in PCa compared to benign areas. In addition, high Cand1 levels were associated with higher Gleason Scores, as well as higher tumor recurrence and decreased overall survival. In line with clinical findings, in vitro experiments in different PCa cell lines revealed that knockdown of Cand1 reduced cell viability and proliferation and increased apoptosis, therefore underlining its role in tumor progression. We also found that the cyclin-dependent kinase inhibitor p21 is significantly upregulated upon downregulation of Cand1. Using bioinformatic tools, we detected genes encoding for proteins linked to mRNA turnover, protein polyubiquitination, and proteasomal degradation to be significantly upregulated in Cand1high tumors. Next generation sequencing of PCa cell lines resistant to the anti-androgen enzalutamide revealed that Cand1 is mutated in enzalutamide-resistant cells, however, with little functional and clinically relevant impact in the process of resistance development. To summarize the present study, we found that high Cand1 levels correlate with PCa aggressiveness.

13.
Gait Posture ; 28(1): 93-100, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18096389

ABSTRACT

The aim of this work was to use bone anchored external markers to describe the kinematics of the tibia, fibula, talus, calcaneus, navicular, cuboid, medial cuneiform, first and fifth metatarsals during gait. Data were collected from six subjects. There was motion at all the joints studied. Movement between the talus and the tibia showed the expected predominance of sagittal plane motion, but the talocalcaneal joint displayed greater variability than expected in its motion. Movement at the talonavicular joint was greater than at the talocalcaneal joint and motion between the medial cuneiform and navicular was far greater than expected. Motion between the first metatarsal and the medial cuneiform was less than motion between the fifth metatarsal and cuboid. Overall the data demonstrated the complexity of the foot and the importance of the joints distal to the rearfoot in its overall dynamic function.


Subject(s)
Forefoot, Human/physiology , Walking/physiology , Adult , Biomechanical Phenomena , Foot Joints/physiology , Humans , Male , Middle Aged , Movement/physiology
14.
Gait Posture ; 28(3): 434-41, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18378454

ABSTRACT

Functional units in the human foot provide a meaningful basis for subdivisions of the entire foot during gait analysis as well as justified simplifications of foot models. The present study aimed to identify such functional units during walking and slow running. An invasive method based upon reflective marker arrays mounted on intracortical pins was used to register motion of seven foot bones. Six healthy subjects were assessed during walking and four of them during slow running. Angle-angle diagrams of corresponding planar bone rotations were plotted against each other and used to establish functional units. Individual functional units were accepted when the joints rotated temporally in phase and either (i) in the same direction, (ii) in the opposite direction, or (iii) when one of the two joints showed no rotation. A functional unit was generalized if all available angle-angle diagrams showed a consistent pattern. A medial array from the navicular to the first metatarsal was found to perform as a functional unit with parts rotating in the same direction and larger rotations occurring proximally. A rigid functional unit comprised the navicular and cuboid. No other functional units were identified. It was concluded that the talus, navicular, and medial cuneiform should neither be regarded as one rigid unit nor as one segment during gait analysis. The first and fifth metatarsals should also be considered separately. It was further concluded that a marker setup for gait analysis should consist of the following four segments: calcaneus, navicular-cuboid, medial cuneiform-first metatarsal, fifth metatarsal.


Subject(s)
Foot/physiology , Gait/physiology , Adult , Calcaneus/physiology , Humans , Male , Middle Aged , Rotation , Talus/physiology , Tarsal Bones/physiology
16.
J Biomech ; 40(12): 2672-8, 2007.
Article in English | MEDLINE | ID: mdl-17368465

ABSTRACT

An accurate kinematic description of the intrinsic articulations of the foot during running has not previously been presented, primarily due to methodological limitations. An invasive method based upon reflective marker arrays mounted on intracortical pins drilled into the bones was used in this study. Four male volunteers participated as subjects. Pins (1.6mm diameter) were inserted under local anaesthetic in the tibia, fibula, calcaneus, talus, navicular, cuboid, medial cuneiform and metatarsals I and V. A 10 camera motion analysis system was used for kinematic data capture and the ground reaction force was simultaneously measured. Segment motion relative to adjacent proximal segments was determined using helical axes projected into the coordinate system of the proximal segment. Coefficients of multiple correlation calculated to determine the strength of association between running style with and without the pins inserted indicated that the subjects had little restriction due to the inserted pins. Individual and mean results were presented for rotations defined in the planes of the proximal segment's coordinate system and showed frontal plane rotation of the talocrural joint (12.2+/-7.1 degrees ), which exceeded that of the subtalar joint (8.9+/-3.2 degrees ). Considerable mobility of the talonavicular joint was found (6.5+/-2.9 degrees , 13.5+/-4.1 degrees and 8.7+/-1.4 degrees in the sagittal, frontal and transverse planes, respectively). Furthermore, little, but non-negligible motion between the fibula and tibia was found (3.3+/-2.4 degrees in the sagittal plane). The presented data are of interest as input for future biomechanical modelling and clinical decision making in particular, concerning joint fusion.


Subject(s)
Fibula/physiology , Foot Bones/physiology , Foot Joints/physiology , Foot/physiology , Running/physiology , Tibia/physiology , Adult , Biomechanical Phenomena , Humans , Male , Middle Aged , Models, Biological
17.
J Biomech ; 40(2): 296-304, 2007.
Article in English | MEDLINE | ID: mdl-16530774

ABSTRACT

Improvement of joint prostheses is dependent upon information concerning the biomechanical properties of the joint. Radiostereometric analysis (RSA) and electromagnetic techniques have been applied in previous cadaver and in vivo studies on the elbow joint to provide valuable information concerning joint motion axes. However, such information is limited to mathematically calculated positions of the axes according to an orthogonal coordinate system and is difficult to relate to individual skeletal anatomy. The aim of this study was to evaluate the in vivo application of a new fusion method to provide three-dimensional (3D) visualization of flexion axes according to bony landmarks. In vivo RSA data of the elbow joint's flexion axes was combined with data obtained by 3D computed tomography (CT). Results were obtained from five healthy subjects after one was excluded due to an instable RSA marker. The median error between imported and transformed RSA marker coordinates and those obtained in the CT volume was 0.22 mm. Median maximal rotation error after transformation of the rigid RSA body to the CT volume was 0.003 degrees . Points of interception with a plane calculated in the RSA orthogonal coordinate system were imported into the CT volume, facilitating the 3D visualization of the flexion axes. This study demonstrates a successful fusion of RSA and CT data, without significant loss of RSA accuracy. The method could be used for relating individual motion axes to a 3D representation of relevant joint anatomy, thus providing important information for clinical applications such as the development of joint prostheses.


Subject(s)
Elbow Joint/diagnostic imaging , Imaging, Three-Dimensional , Tomography, Emission-Computed , Tomography, X-Ray Computed , Adult , Biomechanical Phenomena , Female , Humans , Male , Middle Aged
18.
J Biomech ; 40(15): 3412-23, 2007.
Article in English | MEDLINE | ID: mdl-17631298

ABSTRACT

The aim was to compare kinematic data from an experimental foot model comprising four segments ((i) heel, (ii) navicular/cuboid (iii) medial forefoot, (iv) lateral forefoot), to the kinematics of the individual bones comprising each segment. The foot model was represented using two different marker attachment protocols: (a) markers attached directly to the skin; (b) markers attached to rigid plates mounted on the skin. Bone data were collected for the tibia, talus, calcaneus, navicular, cuboid, medial cuneiform and first and fifth metatarsals (n=6). Based on the mean differences between the three data sets during stance, the differences between any two of the three kinematic protocols (i.e. bone vs skin, bone vs plate, skin vs plate) were >3 degrees in only 35% of the data and >5 degrees in only 3.5% of the data. However, the maximum difference between any two of the three protocols during stance was >3 degrees in 100% of the data, >5 degrees in 73% of the data and >8 degrees in 23% of the data. Differences were greatest for motion of the combined navicular/cuboid relative to the calcaneus and the medial forefoot segment relative to the navicular/cuboid. The differences between the data from the skin and plate protocols were consistently smaller than differences between either protocol and the kinematic data for each bone comprising the segment. The pattern of differences between skin and plate protocols and the actual bone motion showed no systematic pattern. It is unlikely that one rigid body foot model and marker attachment approach is always preferable over another.


Subject(s)
Bones of Lower Extremity/physiology , Foot/physiology , Skin , Walking/physiology , Adult , Biomechanical Phenomena , Humans , Male , Middle Aged
19.
J Bone Joint Surg Br ; 89(9): 1140-3, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17905947

ABSTRACT

The early designs of hip resurfacing implants suffered high rates of early failure, making it impossible to obtain valuable mid-term radiostereophotogrammetric (RSA) results. The metal-on-metal Birmingham Hip Resurfacing arthroplasty has shown promising mid-term results and we present here the first mid-term RSA analysis of a hip resurfacing implant. The analysis was performed in 19 hips at five years post-operatively. The mean acetabular component translation and rotation, and femoral component translation were compared with the previous RSA measurements at two and six months, and one and two years. There was no statistical significance (t-test, p < or = 0.05) between these consecutive movements, indicating the mid-term stability of the implant.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Hip Joint/diagnostic imaging , Hip Prosthesis , Postoperative Complications/diagnostic imaging , Arthroplasty, Replacement, Hip/standards , Follow-Up Studies , Hip Joint/physiopathology , Hip Prosthesis/standards , Humans , Male , Prosthesis Failure , Radiography , Rotation
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