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Tendon pathology in long-standing achillodynia: Biopsy findings in 40 patients

We evaluated biopsy specimens from the Achilles tendon in 40 patients with long-standing achillodynia and an ultrasonographic widened tendon with hypoechogenic areas. We used a standardized protocol to assess the general tendon pathology score of paraffin-embedded specimens stained with HE. Stereologic measurement of the volume density of glycosaminoglycan (GAG)-rich areas, stained with the Alcian blue (pH 2.5)/periodic acid Schiff method (AB/PAS) was performed. 14 specimens obtained at autopsy served as reference material. Abnormal fiber structure and arrangement, focal variations in cellularity, rounded nuclei, decreased collagen stainability and increased non-collagenous extracellular matrix were seen in all biopsy specimens. Slight histopathological changes were noted in half of the controls. Increased vascularity was present in two thirds of the patient specimens and in one third of the controls, and signs of perivascular hemorrhage, as evidenced by hemosiderin deposition in 6/40 of the patients, but in none of the controls. The volume density of GAG-rich areas was higher in the patients 0.47 (0-0.86) than in the controls 0 (0-0.07). Changes in the fiber structure and arrangement, as well as increased amounts of interfibrillar GAG, appear to be characteristic morphological features in Achilles tendons with long-standing achillodynia and ultrasonographic widening. These findings may indicate that achillodynia is due to local disturbances in connective tissue metabolism or circulation or to both.

Etiology, Histopathology, and Outcome of Surgery in Achillodynia

Fifty-eight patients suffering from achillodynia for a median of 12 months (range, 4–240 months) were analyzed using history, clinical findings, ultrasound findings, histopathology, and surgical outcome. Surgical criteria were daily pain or inability to perform sports activity and failure of nonoperative treatment. There were 34 men and 24 women, 31% (18 of 58 patients) of whom had no direct association with sports or vigorous physical activity. Ultrasonography was performed in all cases and showed low echogenous areas (N = 48), increased tendon diameter (N = 40), and/or peritendinous fluid (N = 11). Histopathological evaluation of tendon biopsies, obtained from regions showing pathology at surgery (N = 35), revealed altered fiber structure and arrangement, focal variations in cellularity, extracellular glycosaminoglycans, neovascularization, and/or hyalinization. In no case was inflammatory cell infiltration observed. At a median clinical follow-up of 25 months after surgery, symptoms were decreased in 86% of patients, and 76% had reached a higher activity level compared with the level before surgery. Complications occurred in 13% of operations. In conclusion, achillodynia is not always associated with excessive physical activity. Macroscopic pathologic tendons showed marked histopathologic changes, correlating well with ultrasound findings. Surgical treatment was beneficial in most cases, despite a relatively high complication rate. The etiology and reason for the lack of healing response to rest and nonoperative treatment are unclear.

The temporal responses of protein synthesis, gene expression and cell signalling in human quadriceps muscle and patellar tendon to disuse.

We hypothesized that rates of myofibrillar and patellar tendon collagen synthesis would fall over time during disuse, the changes being accompanied in muscle by decreases in focal adhesion kinase (FAK) phosphorylation and in gene expression for proteolytic enzymes. We studied nine men (22 ± 4 years, BMI 24 ± 3 kg m−2 (means ±s.d.) who underwent unilateral lower leg suspension for 23 days; five were studied between 0 and 10 days and four between 10 and 21 days. Muscle and tendon biopsies were taken in the postabsorptive state at days 0, 10 and 21 for measurement of protein synthesis, gene expression and protein phosphorylation. Muscle cross‐sectional area decreased by 5.2% at 14 days and 10.0% (both P < 0.001), at 23 days, i.e. 0.5% day−1, whereas tendon dimensions were constant. Rates of myofibrillar protein synthesis fell (P < 0.01) from 0.047% h−1 at day 0 to 0.022% h−1 at 10 days without further changes. Tendon collagen synthetic rates also fell (P < 0.01), from 0.052 to 0.023% h−1 at 10 days and then to 0.010% h−1 at 21 days. FAK phosphorylation decreased 30% (P < 0.01) at 10 days. No changes occurred in the amounts/phosphorylation of PKB–P70s6k–mTOR pathway components. Expression of mRNA for MuRF‐1 increased ∼3‐fold at 10 days without changes in MAFbx or tripeptidyl peptidase II mRNA, but all decreased between 10 and 21 days. Thus, both myofibrillar and tendon protein synthetic rates show progressive decreases during 21 days of disuse; in muscle, this is accompanied by decreased phosphorylation of FAK, with no marked increases in genes for proteolytic enzymes.

Eccentric Training of the Gastrocnemius-Soleus Complex in Chronic Achilles Tendinopathy Results in Decreased Tendon Volume and Intratendinous Signal as Evaluated by MRI

Background Satisfactory treatment results have been reported after eccentric calf muscle strength training in patients with chronic Achilles tendinopathy. Hypothesis Magnetic resonance imaging may be a useful adjunct in the evaluation of the effect of 3 months of eccentric calf muscle strength training. Study Design Prospective cohort study. Methods Using magnetic resonance imaging, the Achilles tendons were investigated in 25 patients (16 men and 9 women) ranging in age from 28 to 70 years (median, 51 years) before and after training. Five different magnetic resonance imaging sequences were used. Tendon volume and mean intratendinous signal were calculated using a new seed-growing technique showing 99.3% and 96.6% intraobserver reliability, respectively. The clinical outcome was categorized according to pain level and performance using a questionnaire completed by the patient. Results The eccentric training resulted in a 14% (mean) decrease of tendon volume measured on T1-weighted images, from 6.6 ± 3.1 cm3 to 5.8 ± 2.3 cm3 (P < .05). The intratendinous signal in the symptomatic Achilles tendon measured on proton density-weighted images decreased 23% (mean), from 227 ± 77 signal units to 170 ± 83 signal units (P < .05). The gadolinium contrast agent-enhanced images did not add further value compared with other sequences. Clinical Outcome The clinical outcome was categorized as excellent in 10, good in 3, fair in 5, and poor in 8 patients. The [. Delta]signal correlated significantly with the pain level (P < .05). Conclusions Eccentric training resulted in decreased tendon volume and intratendinous signal and was correlated with an improved clinical outcome. Magnetic resonance imaging techniques can be used as an adjunct to clinical evaluation by monitoring morphologic effects in clinical treatment studies of Achilles tendinopathy.

Poor reproducibility of classification of proximal humeral fractures Additional CT of minor value

Fractures of the proximal humerus can be described using the Neer and AO fracture classifications. To assess the reproducibility and reliability of these classifications, we investigated 26 proximal humeral fractures with both plain radiographs and CT. 5 specialists in orthopedic surgery and 5 specialists in radiology independently classified all radiographs on 2 occasions. There was a moderate agreement between the observers when using the Neer classification, but only a fair agreement with the AO classification. The Neer system had a kappa value of 0.42 and the AO had a value of 0.31 in the first assessment. In the second assessment the kappa values were 0.45 and 0.30, respectively. Intraobserver reproducibility was slight to almost perfect agreement with Neer (kappa range 0.20-0.85) and slight to moderate agreement with AO (kappa range 0.16-0.60). The observers most familiar with shoulder fracture radiographs and shoulder fracture treatment were more consistent in their classifications. We conclude that even with CT, the fracture classifications of Neer and AO have a low consistency. Neither classification system is reproducible enough to allow comparisons of different studies.

Intratendinous Alterations as Imaged by Ultrasound and Contrast Medium-Enhanced Magnetic Resonance in Chronic Achillodynia

Objectives: We performed a comparative study of ultrasonography and gadolinium imaging contrast-enhanced T1-weighted magnetic resonance to evaluate tendon pathology in chronic Achilles tendon disorder. Another main issue was to evaluate the structural basis as defined by histopathology from hypoechoic compared with normoechic areas within the same tendon. Materials and Methods: Twenty patients (16 male, 4 females, median age 40 years) with chronic achillodynia participated in the study. Clinical examination revealed swelling and tenderness localized to the midportion of the Achilles tendon. Contrast medium-enhanced magnetic resonance imaging (CME-MRI) was performed in all patients. Ultrasonography-guided core biopsies were taken from regions with a clear widening of the tendon and a pathologic low-echo signal as well as from normoechoic areas. The specimens were analyzed with a standardized protocol giving a total tendon score (0–24), and a stereologic method for quantification of glycosaminoglycan (GAG)-rich areas. Results: The volume of the intratendinous abnormality was larger in 13 of 20 when imaged by CME-MR (P < 0.05), whereas the shape and enlargement of the tendon per se were similarly imaged by ultrasound (US) and CME-MR. Tendon pathology as imaged by US was graded as severe from hypoechoic regions and moderate from normoechoic regions. The corresponding quantification of GAGs was 0.36 compared with 0.17, respectively (P < 0.001). Conclusion: CME-MR imaging revealed greater sensitivity in demonstrating intratendinous pathology than the ultrasound; this was documented by the larger size of the corresponding lesion and the fact that the pathology was occurring in areas that were considered normal by ultrasonography. US hypoechoic areas showed a markedly abnormal tendon structure including an increased amount of GAG-rich areas. However, moderate pathology was also found in the neighboring normoechogenous areas within the same tendon, indicating a more generalized disorder than depicted by echogenic properties.

3D-radiographic analysis does not improve the Neer and AO classifications of proximal humeral fractures.

The Neer and AO fracture classifications for fractures of the proximal humerus have shown poor reproducibility based on plain radiography. We wanted to investigate whether the addition of 3-dimensional (3D) reconstructions would increase the reproducibility of classification. 7 observers independently classified 24 fractures of the proximal humerus using both plain radiographs, CT and 3D and the classification was repeated 2 months later. There was a moderate interobserver agreement when using the Neer classification, but only a fair agreement with the AO classification. The Neer system had a mean kappa value of 0.44 and the AO had a value of 0.32 for the first assessment. In the second assessment, the mean kappa values were 0.49 and 0.34, respectively. Intraobserver reproducibility was fair to substantial agreement for Neer (kappa range 0.27-0.73) and for AO (kappa range 0.29-0.74). In conclusion, the addition of CT and 3D to plain radiographs did not improve the reproducibility of the classifications of Neer and AO of the proximal humerus.

Immediate Achilles tendon response after strength training evaluated by MRI.

PURPOSE To evaluate the tendon response after acute strength training in chronic Achilles tendinosis using magnetic resonance imaging (MRI). METHODS Twenty-two patients (44 Achilles tendons, 15 males, 8 patients with bilateral symptoms) with a median age of 45 yr (range 28-57 yr) were included in the study. In all patients, both Achilles tendons were examined with MRI before and immediately after a standardized training program. The most painful side underwent 6 sets and 15 repetitions of heavy-loaded eccentric training. The contralateral tendons underwent only concentric loading during the training program. The tendon volume and the intratendinous signal were evaluated and calculated by MRI using a seed-growing technique. RESULTS The immediate response of eccentric loading on the symptomatic tendons resulted in a 12% increase of the tendon volume, evident on T2-WI, from 7.8 +/- 2.0 to 8.8 +/- 2.7 cm3 (P < 0.001), and a 31% increase of the intratendinous signal evident on PD-WI, from 221 +/- 74 to 278 +/- 78 signal units (SU) (P < 0.001). The corresponding sequences on the contralateral concentrically loaded tendons showed an increase of 17% of tendon volume, from 6.1 +/- 1.5 to 7.0 +/- 1.6 cm3 (P < 0.001), and an increase of 27% of the intratendinous signal, from 170 +/- 55 to 211 +/-57 SU (P < 0.001). There was no significant difference of the mean of the increased tendon volume and the intratendinous signal between the eccentrically heavily loaded symptomatic tendons and the concentrically loaded contralateral tendons. CONCLUSIONS Both eccentric and concentric loading of the Achilles tendon resulted in increased total tendon volume and intratendinous signal. This increase may be explained by a higher water content and/or hyperemia in the Achilles tendon during and/or immediately after strength training of the gastrocnemius-soleus complex.

MR imaging in chronic achilles tendon disorder

Objectives: the primary objective was to compare 4 imaging sequences (T1-weighted, T2-weighted, proton density, and T1-weighted with gadolinium contrast agent enhancement) with regard to intratendinous signal abnormality in patients with achillodynia. the secondary objective was to relate the images to the clinical symptoms and histopathological findings Material and Methods: Twenty patients (16 men, 4 women, median age 40 years) with chronic achillodynia participated in the study. the symptoms prohibited activity and clinical examination revealed swelling and tenderness 1.5–6 cm proximal to the Achilles tendon insertion. of the 20 patients: 5 had bilateral achillodynia, 4 had had previous contralateral Achilles tendon disorder, and 11 had never had symptoms in the contralateral tendon region. These 11 tendons served as controls for comparison MR imaging was performed on a superconductive 1.5 T unit. Both Achilles tendons were examined (n=40) at the same time, and multiple sagittal and transversal images were obtained. the corresponding sections on these images were visually graded according to both extension and level of MR signal intensity. Tissue was obtained for microscopic examination from the most symptomatic side in all patients (n=20) Results: T1-weighted images following gadolinium contrast medium enhancement proved to be the best method by which to visualize intratendinous signal abnormality. This sequence revealed signal abnormality in 24/25 symptomatic tendons and in 1/11 control tendons (p>0.001). Histopathological examination showed an increased noncollagenous extracellular matrix and altered fiber structure in the lesions corresponding to the contrast-enhanced areas Conclusion: Gadolinium enhancement improved the imaging of intratendinous signal abnormality on T1-weighted images. There was a high level of extracellular glycosaminoglycans, which are highly-fixed negatively-charged macromolecules with extreme water-retaining capacity and which may have contributed to the enhancement by the gadolinium contrast agent

PATHOLOGY OF THE ACHILLES TENDON IN ASSOCIATION WITH CIPROFLOXACIN TREATMENT

Achilles tendon pain or rupture after fluoroquionolone treatment has been described as an uncommon adverse effect. We report two patients with ciprofloxacin-associated Achilles tendon disease, one with histopathological examination. Microscopic evaluation showed irregular collagen fiber arrangement, hypercellularity, and increased interfibrillar glycosaminoglycans. These pathological features are also seen in tendon overuse injuries in athletes.