Long-term results of arthroscopic and mini-open repair of small- to medium-size full-thickness rotator cuff tears.

BACKGROUND: This retrospective cohort study evaluated functional outcome and structural integrity after arthroscopic- or mini-open repair of small- to medium-size rotator cuff tears assessed at long-term follow-up. METHODS: All patients operated between 2001 and 2004 were invited to participate. Functional outcome was measured by Constant-Murley Score, Disability of Arm, Shoulder and Hand and Oxford Shoulder Score. Quality of life was assessed with EuroQol Health 5 Dimension. Patient satisfaction was assessed in terms of pain and overall result. Structural integrity of the rotator cuff repair was determined using ultrasound. RESULTS: Of the eligible 62 patients, 44 patients were available for follow-up. After a mean of 11.3 years, 76% of the patients had good to excellent functional outcome on the Constant-Murley Score (median 82, range 29-95). The majority of patients reported good results on both Disability of Arm, Shoulder and Hand and Oxford Shoulder Score (median Disability of Arm, Shoulder and Hand 5.0, range 1.0-54; median Oxford Shoulder Score 19, range 13-39). The quality of life was also good (mean EuroQol Health 5 Dimension utility score 0.88, standard deviation 0.12). Eighty per cent was satisfied with the overall result. Ultrasound examination revealed structural integrity in 76% of all cases. CONCLUSION: This study shows that functional outcome is good and structural integrity is high for the majority of patients 11.3 years after repair of small- to medium-size rotator cuff lesions.

Gastro-Intestinal Tolerance and Renal Safety of Protein Oral Nutritional Supplements in Nursing Home Residents: A Randomized Controlled Trial.

BACKGROUND/OBJECTIVE: High protein oral nutritional supplements (ONS) are regularly prescribed to undernourished patients; however usage of these in older adults is being discussed, as their renal function might have declined with age. Therefore, the aim of the current study was to evaluate the effects of 8 week long consumption of high protein ONS on the renal function of nursing home residents in need of supplementation. Furthermore, within the same setup, differences in gastro-intestinal tolerance between a standard and a more concentrated version of an ONS were investigated. DESIGN: Randomized, controlled, single-blind, parallel-group, multi-country trial (NTR2565). SETTING: Nursing home. PARTICIPANTS: 67 nursing home residents in need of ONS (energy-dense, small volume group n=32; standard volume group n=35). INTERVENTION: Protein supplementation was provided by either a standard (200ml, 300kcal, 20g protein) or an energy-dense, small volume (125ml, 300kcal, 18g protein) ONS during the 8 week long study. MEASUREMENTS: Primary outcome was gastro-intestinal tolerance, assessed by daily stool frequency and consistency, and occurrence and intensity of self-reported gastro-intestinal symptoms. Safety was measured via the occurrence of (serious) adverse events, vital signs, as well as liver- and kidney function monitoring. RESULTS: No clinically relevant and, except for flatulence, no statistically significant differences in gastro-intestinal tolerance were observed between groups. No significant difference between groups was found for estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio at baseline and week 8, nor for the changes from baseline. Adverse events and the changes in monitored renal parameters over the study period did not point to a deterioration of renal function. CONCLUSION: High protein ONS seems to be well-tolerated and safe; there is no indication that it affects renal function in nursing home residents, including patients with stage 3 chronic kidney disease, under the conditions tested. Results did not suggest a difference in the effect on renal function between standard and energy-dense small volume ONS format.

Correction of ankle valgus by hemiepiphysiodesis using the tension band principle in patients with multiple hereditary exostosis.

BACKGROUND: Ankle valgus is a common deformity in patients with multiple hereditary exostoses (MHE) and a potential risk factor for early degenerative arthritis. In children, medial hemiepiphysiodesis of the distal tibia is a relatively simple surgical technique used to correct this deformity. We present here the first results of applying this procedure using the eight-Plate guided growth system (eight-Plate) for growth guidance. METHODS: Between 2006 and 2011 we performed hemiepiphysiodesis of the distal medial tibia in 30 ankles of 18 children with MHE using the eight-Plate. Weight-bearing total leg radiographs were obtained preoperatively, during follow-up and at the time of implant removal or when the distal tibial physis had closed. The lateral distal tibia angle (LDTA) was measured and fibular shortening assessed using the Malhotra classification. To evaluate the effect of hemiepiphysiodesis, we correlated the LDTA with age. RESULTS: The mean age at time of surgery was 12.6 (range 9.5-15.0) years, and the mean preoperative LDTA was 76.9° (range 68.5°-83.5°). During follow-up, the implant was removed in 12 extremities and the physis had closed in 18 extremities. The mean LDTA at the time of implant removal or at closure of the physis was 83.6° (range 76.5°-90.0°). Mean correction of LDTA was 6.9° after a mean follow-up period of 22 (range 3-43) months. During follow-up, no changes in the Malhotra classification were found in any of the patients. Correction of the valgus deformity of the ankle was significantly correlated (r = -0.506) (p = 0.004) with age in all patients. CONCLUSION: Temporary medial hemiepiphyseodesis of the distal tibia seems to be an effective strategy for correcting ankle valgus in children with MHE. Timing of the intervention is, however, of importance. Hemiepiphyseodesis alone has no effect on the Malhotra classification. LEVEL OF EVIDENCE: IV, retrospective review.

Tears of the supraspinatus tendon: assessment with indirect magnetic resonance arthrography in 67 patients with arthroscopic correlation.

BACKGROUND: Magnetic resonance (MR) arthrography is generally regarded as the gold standard for shoulder imaging. As an alternative to direct MR arthrography, the less invasive indirect MR arthrography technique was proposed, offering logistic advantages because fluoroscopic or ultrasonographic guidance for joint injection is not required. PURPOSE: To assess the diagnostic performance of indirect MR arthrography in the diagnosis of full- and partial-thickness supraspinatus tears in a symptomatic population. MATERIAL AND METHODS: Two radiologists with different levels of experience independently and retrospectively interpreted indirect MR (1.5T) arthrograms of the shoulder obtained in 67 symptomatic patients who underwent subsequent arthroscopy. On MR, the supraspinatus tendon was evaluated for full- or partial-thickness tear. With arthroscopy as the standard of reference, sensitivity, specificity, and diagnostic accuracy of indirect MR arthrography in the detection of full- and partial-thickness tears of the supraspinatus tendon was calculated. Kappa (kappa) statistics were used for the assessment of the agreement between arthroscopic and imaging findings and for the assessment of interobserver agreement. RESULTS: For full-thickness tears of the supraspinatus tendon, sensitivities, specificities, and accuracies exceeded 90% for both observers, with excellent interobserver agreement (kappa = 0.910). For partial-thickness tears, sensitivities (38-50%) and accuracies (76-78%) were poor for both reviewers, and interobserver agreement was moderate (kappa = 0.491). Discrepancies between MR diagnosis and arthroscopy were predominantly observed with small partial-thickness tears. CONCLUSION: Indirect MR arthrography is highly accurate in the diagnosis of full-thickness rotator cuff tears. However, the diagnosis of partial-thickness tears with indirect MR arthrography remains faulty, because exact demarcation of degenerative change and partial rupture is difficult. On the basis of the above findings, we do not recommend indirect MR arthrography on patients for whom rotator cuff disease is suspected clinically.

Magnetic resonance imaging after surgery for shoulder instability.

Interpretation of MR imaging of the shoulder after instability repair can be significantly hampered by (susceptibility) artifacts and/or distortion of normal anatomy. Knowledge of the surgical procedures performed including the (ferromagnetic) materials used is important to adjust the imaging protocol, in order to reduce artifacts. MR arthrography is probably the optimal tool for assessment of postoperative capsular-labral structures and rotator cuff defects. More general postoperative complications can be determined or excluded using conventional fast spin echo sequences with or without fat-suppression.

MR arthrography in glenohumeral instability.

The impact of accurate imaging in the work-up of patients with glenohumeral instability is high. Results of imaging may directly influence the surgeon's strategy to perform an arthroscopic or open treatment for (recurrent) instability. Magnetic resonance (MR) imaging, and MR arthrography in particular, is the optimal technique to detect, localize and characterize injuries of the capsular-labrum complex. Besides TI-weighted sequences with fat suppression in axial, oblique sagital and coronal directions, an additional series in abduction and exoroation position is highly advocated. This ABER series optimally depicts abnormalities of the inferior capsular-labrum complex and partial undersurface tears of the spinatus tendons. Knowledge of different anatomical variants that may mimic labral tears and of variants of the classic Bankart lesion are useful in the analysis of shoulder MR arthrograms in patients with glenohumeral instability.

MR arthrography of the rotator cuff.

This article addresses the role of MR arthrography in the evaluation of the rotator cuff, including impingement, tendon degeneration and rotator cuff tears. Additionally, pathologic conditions of the long head of the biceps tendon, and mimickers of rotator cuff pathology are discussed as well. The drawbacks of conventional MR imaging and indirect MR arthrography, compared to the merit of direct MR arthrography are emphasized. The manuscript focusses on the potential clinical consequences of each finding and summarizes which relevant imaging findings should be reported by the radiologist.

Chronic quercetin exposure affects fatty acid catabolism in rat lung.

Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by the long-term quercetin intervention. Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR. In addition, free fatty acid levels were decreased in rats fed the quercetin diet, confirming that quercetin affects fatty acid catabolism. This in vivo study demonstrates for the first time that fatty acid catabolism is a relevant process that is affected in rats by chronic dietary quercetin.

Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua.

An important group of antimalarial drugs consists of the endoperoxide sesquiterpene lactone artemisinin and its derivatives. Only little is known about the biosynthesis of artemisinin in Artemisia annua L., particularly about the early enzymatic steps between amorpha-4,11-diene and dihydroartemisinic acid. Analyses of the terpenoids from A. annua leaves and gland secretory cells revealed the presence of the oxygenated amorpha-4,11-diene derivatives artemisinic alcohol, dihydroartemisinic alcohol, artemisinic aldehyde, dihydroartemisinic aldehyde and dihydroartemisinic acid. We also demonstrated the presence of a number of biosynthetic enzymes such as the amorpha-4,11-diene synthase and the--so far unknown--amorpha-4,11-diene hydroxylase as well as artemisinic alcohol and dihydroartemisinic aldehyde dehydrogenase activities in both leaves and glandular trichomes. From these results, we hypothesise that the early steps in artemisinin biosynthesis involve amorpha-4,11-diene hydroxylation to artemisinic alcohol, followed by oxidation to artemisinic aldehyde, reduction of the C11-C13 double bond to dihydroartemisinic aldehyde and oxidation to dihydroartemisinic acid.

Alveolar soft-part sarcoma responding to interferon alpha-2b.

A 23-year-old woman with an alveolar soft-part sarcoma of her calf with pulmonary metastases unresponsive to chemotherapy is described. Interferon (IFN) alpha-2b induced an impressive tumour response still ongoing after IFN treatment had to be stopped because of a psychosis. An explanation of this effect is still speculative.

[Non-traumatic myositis ossificans circumscripta in the teres major muscle]. / Niet-traumatisch ontstane myositis ossificans circumscripta in de M. teres major.

A 49-year-old male presented with a painful progressive swelling in his right axillar region, without further complaints, which had been present for 2 weeks. On radiological examination a peripheral circumferential zone of mineralisation was seen in the right teres major muscle. An incision biopsy specimen showed a lesion of fibroblastic tissue in which areas of osteoid and fragmented lamellar bone tissue, without signs of malignancy. The diagnosis was myositis ossificans circumscripta. This is a rare benign ossifying lesion in skeletal muscles, mostly caused by a trauma and with an average age of occurrence between 20 and 30 years old. It must be differentiated from extra-skeletal osteosarcoma. The pathogenesis is unknown. Because it is a benign and self-limiting disorder, surgical excision is only necessary in case of mechanical hindrance. The patient's swelling partially regressed and he had no further complaints.

Dry powder inhalation of antibiotics in cystic fibrosis therapy, part 1: development of a powder formulation with colistin sulfate for a special test inhaler with an air classifier as de-agglomeration principle.

The aim of this study was to investigate the pulmonary administration of antibiotics as dry powder to patients with cystic fibrosis (CF), as an alternative for nebulization. This part of the study describes the development of a powder formulation with colistin sulfate as model substance. The aim of the new dosage form was to increase pulmonary deposition, therapeutic efficiency and, by that, compliance by the CF patients. A physical powder mixture of colistin and a size fraction of lactose (106-150 microm) was prepared and the mixture was optimized with respect to colistin content (83.3%) for use in a special test inhaler. A laser diffraction apparatus with special inhaler adapter was applied for analysis of the size distribution of the aerosol cloud from the inhaler. The size distributions of the aerosol clouds from the test inhaler at flow rates between 30 and 60 l/min for the optimized formulation showed nearly the same median diameter as that for the primary drug particles. But the X(100)-value was much lower, because of an effective large particle separation from the inspiratory air by an air classifier in the test inhaler. The results suggest that dry powder inhalation might be a suitable and highly efficient alternative for nebulization of antibiotic drugs in CF therapy.

Unaltered perception of dyspnoea during treatment with long-acting beta2-agonists.

There is the possibility that during treatment with inhaled long-acting beta2-agonists that a loss of perception of dyspnoea might occur and that the forced expiratory volume in one second (FEV1) might fall precipitously during bronchial provocation. This study investigated these possibilities during methacholine provocation, continued until there was > or =30% fall in FEV1, mimicking a moderate asthma attack. Nineteen asthmatic patients were asked to score their dyspnoea as a Borg score during provocation with methacholine. One hour prior to this provocation, the patients used the last morning dose of 14 days treatment with either formoterol (twice daily 24 microg by Turbuhaler), salmeterol (twice daily 100 microg by Diskhaler) and placebo in a double-blind, randomized, double-dummy, cross-over design. The perception of dyspnoea, expressed as the Borg score divided by the change in FEV1 at > or =30% fall in FEV1, was similar on the three test days at 0.067, 0.076 and 0.074%(-1) after formoterol, salmeterol and placebo treatment, respectively (p=0.16). The slope of the methacholine dose response curve did not differ (p=0.52). In conclusion, no suggestion was found for an abnormal perception of dyspnoea or an exaggerated fall in forced expiratory volume in one second during provocation with methacholine under long-acting beta2-agonist treatment.

Compliance with inhaled glucocorticoids and concomitant use of long-acting beta2-agonists.

We investigated whether treatment with a long-acting beta2-agonist (LAbeta2) is associated with a decrease in patient compliance with regard to inhalation corticosteroids (ICS). Date on prescriptions collected by 15,760 patients suffering from airways disease were provided by 69 Dutch pharmacies. All prescriptions of ICS and LAbeta2 were analysed and divided in four groups by LAbeta2 use during 1997 and 1998. Date from 15,760 patients were available. In the 10,929 patients not treated with LAbeta2, compliance decreased slightly but not significantly. In 3281 patients receiving LAbeta2 compliance also decreased slightly but not significantly. In 404 patients, who used a LAbeta2 in 1997 and discontinued treatment in 1998, the compliance fell significantly (P<0.05). In 1147 patients who started to use a LAbeta2 in 1998, compliance with ICS significantly improved (P<0.05). These results suggest that the regular use of LAbeta2 improves compliance with ICS. Therefore, the concern that compliance with inhaled corticosteroid therapy will decrease under concomitant use of LAbeta2 appear to be unfounded.

Decreased bronchodilating effect of salbutamol in relieving methacholine induced moderate to severe bronchoconstriction during high dose treatment with long acting beta2 agonists.

BACKGROUND: In vitro the long acting beta2 agonist salmeterol can, in contrast to formoterol, behave as a partial agonist and become a partial antagonist to other beta2 agonists. To study this in vivo, the bronchodilating effect of salbutamol was measured during methacholine induced moderate to severe bronchoconstriction in patients receiving maintenance treatment with high dose long acting beta2 agonists. METHODS: A randomised double blind crossover study was performed in 19 asthmatic patients with mean forced expiratory volume in one second (FEV1) of 88.4% predicted and median concentration of methacholine provoking a fall in FEV1 of 20% or more (PC(20)) of 0.62 mg/ml at entry. One hour after the last dose of 2 weeks of treatment with formoterol (24 microg twice daily by Turbuhaler), salmeterol (100 microg twice daily by Diskhaler), or placebo a methacholine provocation test was performed and continued until there was at least a 30% decrease in FEV1. Salbutamol (50 microg) was administered immediately thereafter, followed by ipratropium bromide (40 microg) after a further 30 minutes. Lung function was monitored for 1 hour after provocation. RESULTS: There was a significant bronchodilating and bronchoprotective effect after 2 weeks of active treatment. The dose of methacholine needed to provoke a fall in FEV1 of > or = 30% was higher after pretreatment with formoterol (2.48 mg) than with salmeterol (1.58 mg) or placebo (0.74 mg). The difference between formoterol and salmeterol was statistically significant: 0.7 doubling dose steps (95% CI 0.1 to 1.2, p=0.016). The immediate bronchodilating effect of subsequently administered salbutamol was significantly impaired after pretreatment with both drugs (p<0.0003 for both). Three minutes after inhaling salbutamol the increase in FEV1 relative to the pre-methacholine baseline was 15.8%, 7.3%, and 5.5% for placebo, formoterol and salmeterol, respectively (equivalent to increases of 26%, 14%, and 12%, respectively, from the lowest FEV1 after methacholine). At 30 minutes significant differences remained, but 1 hour after completing the methacholine challenge FEV1 had returned to baseline values in all three treatment groups. CONCLUSION: Formoterol has a greater intrinsic activity than salmeterol as a bronchoprotective agent, indicating that salmeterol is a partial agonist compared with formoterol in contracted human airways in vivo. Irrespective of this, prior long term treatment with both long acting beta2 agonists reduced the bronchodilating effect of an additional single dose of salbutamol equally, indicating that the development of tolerance or high receptor occupancy overshadowed any possible partial antagonistic activity of salmeterol. Patients on regular treatment with long acting beta2 agonists should be made aware that an additional single dose of a short acting beta2 agonist may become less effective.

Contrast-enhanced magnetic resonance imaging of bone marrow.

In the assessment with magnetic resonance (MR) imaging of bone marrow disorders, the use of contrast agents is usually not critical because T1-weighted spin-echo and fat-suppressed sequences (STIR or fat-sat intermediate weighted) are robust and largely available techniques for depiction of neoplastic and non-neoplastic lesions of the bone marrow. This article discusses the characteristics of dynamic contrast-enhanced MR imaging of bone marrow edema, ischemia, and neoplasm. It emphasizes its value in staging and in monitoring of response to chemotherapy of several bone tumors. These fast dynamic contrast-enhanced techniques do not allow differentiation between benign and malignant primary osseous tumors because the biologic behavior rather than the malignant potential of these lesions is reflected.

Malignant progression in multiple enchondromatosis (Ollier's disease): an autopsy-based molecular genetic study.

Multiple enchondromatosis (Ollier's disease) is a nonhereditary disease characterized by multiple central (medullary) cartilaginous bone tumors of unknown pathogenesis. It usually involves the extremities with a unilateral predominance, and sarcomatous transformation may occur. We report an autopsy-based genetic study of a 34-year-old man presenting in early adolescence with multiple enchondromas of the extremities, predominantly left-sided, compatible with Ollier's disease. Twelve years after presentation, malignant transformation to a high grade chondrosarcoma occurred in a tibial enchondroma. The patient died after widespread metastatic disease. Loss of heterozygosity (LOH), in the tibial chondrosarcoma and its metastases, was identified exclusively on chromosome bands 13q14 and 9p21, while being absent in the femoral enchondroma analyzed. Similarly, p53 overexpression was identified immunohistochemically in the tibial chondrosarcoma and its metastases, while being absent in the femoral enchondroma; LOH at 17p13 however, was not demonstrable. It is hypothesized that inactivation of putative tumor suppressor genes at 9p21 and 13q14, and overexpression of p53, identified in the chondrosarcoma and its metastases, but absent in enchondroma, may be related to sarcomatous transformation in Ollier's disease.

Detection of areas with viable remnant tumor in postchemotherapy patients with Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokinetic modeling.

An approach is presented for monitoring the effects of neoadjuvant chemotherapy in patients with Ewing's sarcoma using dynamic contrast-enhanced perfusion magnetic resonance (MR) images. For that purpose, we modify the three-compartment pharmacokinetic permeability model introduced by Tofts et al. (Magn Reson Med 1991;17:357-67) to a two-compartment model. Perfusion MR images acquired using an intravenous injection with Gadolinium (Gd-DTPA) are analyzed with this two-compartment pharmacokinetic model as well as the with an extended pharmacokinetic model that includes the (local) arrival time t(0) of the tracer as an endogenous (estimated) parameter. For each MR section, a wash-in parameter associated with each voxel is estimated twice by fitting each of the two pharmacokinetic models to the dynamic MR signal. A comparison of the two wash-in parametric images (global versus local arrival time) with matched histologic macroslices demonstrates a good correspondence between areas with viable remnant tumor and a high wash-in rate. This can be explained by the high number and permeability of the (leaking) capillaries in viable tumor tissue. The novel pharmacokinetic model based on a local arrival time of tracer results in the best fit of the wash-in rate, the most important factor discerning viable from nonviable tumor components. However, parameter estimates obtained with this model are also more sensitive to noise in the MR signal. The novel pharmacokinetic model resulted in a sensitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The model based on a global arrival time gave sensitivities between 0.33 and 0.77 and specificities between 0.58 and 0.99. Both statistics are computed as the fraction of correctly labeled voxels (viable or nonviable tumor) within a specified ROI, which delineates the tumor. We conclude that the added value of estimating the local arrival time of tracer first manifests itself for moderate noise levels in the MR signal. The novel pharmacokinetic model should moreover be preferred when pharmacokinetic modeling is applied on the average signal intensity within a ROI, where noise has less effect on the fitted parameters.