Ultrastructural mitochondrial alterations in Equine myopathies of unknown origin.

Background: Very few mitochondrial myopathies have been described in horses. Objective: To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin. Materials & methods: Biopsies of vastus lateralis of the Musculus quadriceps femoris were taken predominantly immediately post mortem and processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses. Results: Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance. Conclusions: Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed. Practical applications: The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

Proximal Femoral Osteotomies with the Paediatric Hip Plate (LCP): Valgus osteotomy.

OBJECTIVE Proximal femoral osteotomy with stable fixation and sufficient correction. Low complication rates due to exact preoperative planning. INDICATIONS Congenital or traumatic femoral neck pseudarthrosis. Coxa vara. CONTRAINDICATIONS None. In severe deformities, a single femoral osteotomy may not solve the problem; thus, additional correction, e.g., a pelvic osteotomy, is required. SURGICAL TECHNIQUE Correct planning of the correction angle. Lateral approach. Subperiosteal detachment of vastus lateralis muscle. Place guide wire on the femoral neck to judge anteversion. Insert positioning wire 5 mm distal to trochanteric physis. Insert 2.8 mm Kirschner wire in the femoral neck. Osteotomy of the femur after marking the rotation by Kirschner wires or oscillating saw. Slide LC plate over Kirschner wires. Replace Kirschner wires with screws. Reduction of the femoral shaft to the plate with bone forceps. Definitive fixation of the plate to the femoral shaft by cortex or locking screws. Readaptation of vastus lateralis muscle over the plate. POSTOPERATIVE MANAGEMENT Partial weightbearing for 4-6 weeks depending on the age of the patient without any external fixation (e. g. cast) is possible. RESULTS Recent studies support the authors' findings of sufficient correction and stable fixation after proximal femoral osteotomy with the LCP pediatric hip plate. Low complication rates and stable fixation.

Angiogenesis-related ultrastructural changes to capillaries in human skeletal muscle in response to endurance exercise

The ultrastructure of capillaries in skeletal muscle was morphometrically assessed in vastus lateralis muscle (VL) biopsies taken before and after exercise from 22 participants of two training studies. In study 1 (8 wk of ergometer training), light microscopy revealed capillary-fiber (C/F) ratio (+27%) and capillary density (+16%) to be higher (P ≤ 0.05) in postexercise biopsies than in preexercise biopsies from all 10 participants. In study 2 (6 mo of moderate running), C/F ratio and capillary density were increased (+23% and +20%; respectively, P ≤ 0.05) in VL biopsies from 6 angiogenesis responders (AR) after training, whereas 6 nonangiogenesis responders (NR) showed nonsignificant changes in these structural indicators (-4%/-4%, respectively). Forty capillary profiles per participant were evaluated by point and intersection counting on cross sections after transmission electron microscopy. In study 1, volume density (Vv) and mean arithmetic thickness (T) of endothelial cells (ECs; +19%/+17%, respectively) and pericytes (PCs; +20%/+21%, respectively) were higher (P ≤ 0.05), whereas Vv and T of the pericapillary basement membrane (BM) were -23%/-22% lower (P ≤ 0.05), respectively, in posttraining biopsies. In study 2, exercise-related differences between AR and NR-groups were found for Vv and T of PCs (AR, +26%/+22%, respectively, both P ≤ 0.05; NR, +1%/-3%, respectively, both P > 0.05) and BM (AR, -14%/-13%, respectively, both P ≤ 0.05; NR, -9%/-11%, respectively, P = 0.07/0.10). Vv and T of ECs were higher (AR, +16%/+18%, respectively; NR, +6%/+6%, respectively; all P ≤ 0.05) in both groups. The PC coverage was higher (+13%, P ≤ 0.05) in VL biopsies of individuals in the AR group but nonsignificantly altered (+3%, P > 0.05) in those of the NR group after training. Our study suggests that intensified PC mobilization and BM thinning are related to exercise-induced angiogenesis in human skeletal muscle, whereas training per se induces EC-thickening.

Capillary growth, ultrastructure remodelling and exercise training in skeletal muscle of essential hypertensive patients

AIM The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. METHODS To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. RESULTS At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 μm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). CONCLUSION Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.

[Medium-term results after m. vastus medialis obliquus-plasty for lateral patellar dislocation]

Progressive retropatellar arthrosis is often seen in dated rigid distal realignment (i.e. osteotomy of tuberositas) at long-term follow-ups. Therefore, operations for lateral dislocation of the patella are still discussed controversially. Dynamic, proximal realignments seem to have lower rates of arthrosis but higher rates of redislocation. Recently, in anatomic and biomechanic studies, the m. vastus medialis obliquus (vmo) was found to be one of the most important proximal restraints to lateral dislocation of the patella.A total of 28 patients (mean age 21.5 years) were treated between 1994 and 2003 with a plasty of the vmo for lateral patellar dislocation. The technique was performed for most etiologies of femoropatellar instability.For this proximal soft tissue technique, the muscle tendon is detached from its patellar insertion. Subsequently, the tendon is reinserted at the patella 10-15 mm more distally and fixed with Mitek anchors. Full weight bearing in extension is possible immediately after surgery. An active vastus medialis training is started after 6 weeks.Of the patients, 27 were evaluated clinically and radiologically in 2004 (a mean of 5 years postoperatively). A total of 83% of the patients estimated the result to be good or excellent, 10% were satisfied and 7% were discontent. The mean Lysholm-Knee-Score was 83.1 points. Two patients suffered a patella redislocation (7%). A statistically significant improvement of the congruence angle was noted in the radiographs, even in medium-term controls. In 89% of the cases no or only little retropatellar arthrosis was observed. These 5 year results are comparable to those of other techniques for distal or proximal realignments. The rate of redislocation was below average. Compared to the rate of retropatellar arthrosis in long-term results of rigid distal realignment, our patients demonstrated a relative low rate after 5 years. We attribute this to the minimal interference in physiological joint mechanics and to the restored anatomy. In terms of future long-term results, our findings are promising. The idea of a proximal dynamic stabilization and the causal operative approach at the origin of pathology using vmo-plasty was confirmed in recent anatomic and biomechanic studies. Over or under correction of soft tissues could be adapted. More rigid techniques of distal realignment do not allow an adaptation to this extent and can lead to prearthrotic hyperpression in the medial femoropatellar and femorotibial joints.

Neuromechanical gait adaptations in women with joint hypermobility - an exploratory study

BACKGROUND Joint hypermobility is known to be associated with joint and muscle pain, joint instability and osteoarthritis. Previous work suggested that those individuals present an altered neuromuscular behavior during activities such as level walking. Therefore, the aim of this study was to explore the differences in ground reaction forces, temporal parameters and muscle activation patterns during gait between normomobile and hypermobile women, including symptomatic and asymptomatic hypermobile individuals. METHODS A total of 195 women were included in this cross-sectional study, including 67 normomobile (mean 24.8 [SD 5.4] years) and 128 hypermobile (mean 25.8 [SD 5.4] years), of which 56 were further classified as symptomatic and 47 as asymptomatic. The remaining 25 subjects could not be further classified. Ground reaction forces and muscle activation from six leg muscles were measured while the subjects walked at a self-selected speed on an instrumented walkway. Temporal parameters were derived from ground reaction forces and a foot accelerometer. The normomobile and hypermobile groups were compared using independent samples t-tests, whereas the normomobile, symptomatic and asymptomatic hypermobile groups were compared using one-way ANOVAs with Tukey post-hoc tests (significance level=0.05). FINDINGS Swing phase duration was higher among hypermobile (P=0.005) and symptomatic hypermobile (P=0.018) compared to normomobile women. The vastus medialis (P=0.049) and lateralis (P=0.030) and medial gastrocnemius (P=0.011) muscles showed higher mean activation levels during stance in the hypermobile compared to the normomobile group. INTERPRETATION Hypermobile women might alter their gait pattern in order to stabilize their knee joint.

Standardized protocol for a depletion of intramyocellular lipids (IMCL)

Intramyocellular lipids (IMCL) are flexible fuel stores that are depleted by physical exercise and replenished by fat intake. IMCL or their degradation products are thought to interfere with insulin signaling thereby contributing to insulin resistance. From a practical point of view it is desirable to deplete IMCL prior to replenishing them. So far, it is not clear for how long and at which intensity subjects have to exercise in order to deplete IMCL. We therefore aimed at developing a standardized exercise protocol that is applicable to subjects over a broad range of exercise capacity and insulin sensitivity and allows measuring reliably reduced IMCL levels.Twelve male subjects, including four diabetes type 2 patients, with wide ranges of exercise capacity (VO(2)peak per total body weight 27.9-55.8 ml x kg(-1) x min(-1)), insulin sensitivity (glucose infusion rate per lean body mass 4.7-15.3 mg x min(-1) x kg(-1)), and BMI (21.7-31.5 kg x m(-2)), respectively, were enrolled. Using (1)H magnetic resonance spectroscopy ((1)H-MRS), IMCL was measured in m.tibialis anterior and m.vastus intermedius before and during a depletion protocol of a week, consisting of a moderate additional physical activity (1 h daily at 60% VO(2)peak) and modest low-fat (10-15%) diet.Absolute IMCL-levels were significantly reduced in both muscles during the first 3 days and stayed constant for the next 3 days of an identical diet/exercise-scheme. These reduced IMCL levels were independent of insulin sensitivity, yet a tendency to lower depleted IMCL levels has been observed in subjects with higher VO(2)peak.The proposed protocol is feasible in subjects with large differences in exercise capacity, insulin sensitivity, and BMI, leading to reduced IMCL levels that neither depend on the exact duration of the depletion protocol nor on insulin sensitivity. This allows for a standardized preparation of IMCL levels either for correlation with other physiological parameters or for replenishment studies.