Improvement of thigh muscles by neuromuscular electrical stimulation in patients with refractory heart failure: a single-blind, randomized, controlled trial

OBJECTIVE: To determine the impact of an 8-wk neuromuscular stimulation program of thigh muscles on strength and cross-sectional area in patients with refractory heart failure listed for transplantation. DESIGN: Forty-two patients with a stable disease course were assigned randomly to a stimulation group (SG) or a control group (CG). The stimulation protocol consisted of biphasic symmetric impulses with a frequency of 50 Hz and an on/off regime of 2/6 sec. RESULTS: Primary outcome measures were isometric and isokinetic thigh muscle strength and muscle cross-sectional area. Our results showed an increase of muscle strength by mean 22.7 for knee extensor and by 35.4 for knee flexor muscles. The CG remained unchanged or decreased by -8.4 in extensor strength. Cross-sectional area increased in the SG by 15.5 and in the CG by 1.7. CONCLUSIONS: Activities of daily living as well as quality of life increased in the SG but not in the CG. Subscales of the SF-36 increased significantly in the SG, especially concerning physical functioning by +7.5 (1.3-30.0), emotional role by +33.3 (0-66.6), and social functioning by +18.8 (0-46.9), all P < 0.05. Neither a change nor a decrease was observed in the CG. Neuromuscular electrical stimulation of thigh muscles in patients with refractory heart failure is effective in increasing muscle strength and bulk and positively affects the perception of quality of life and activities of daily living.     

Maturation of early visual processing investigated by a pattern-reversal habituation paradigm is altered in migraine

Evidence for a disturbed maturation of information processing in migraine came recently from evoked and event-related potential studies during childhood. In adult migraineurs, deficient habituation is proposed as principal interictal abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This study investigated response and habituation to pattern-reversal VEPs and its maturation in 102 children with primary headache (migraine with and without aura, tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of N180 latency from pre- to postpubertal age reflects maturation and was clearly present in controls but lessened in migraineurs. N180 latency was prolonged in migraineurs without aura from 12 years onwards. Habituation did not differ between groups. In conclusion, diminished N180 latency reduction with age in migraineurs gives further evidence that maturation of visual information processing is altered in migraine. Deficient habituation to pattern-reversal VEPs could not be confirmed during childhood migraine.     

Effects of LDL-immunoapheresis on plasma concentrations of vitamin E and carotenoids in patients with familial hypercholesterolemia

Recently very potent extracorporeal cholesterol-lowering treatment options have become available for patients with hypercholesterolemia. LDL immunoapheresis treatment selectively removes LDL and lipoprotein(a) from the circulation. Since LDL is the major carrier of lipophilic antioxidants in plasma, the purpose of the present study was to assess the effects of a single LDL apheresis treatment on plasma concentrations of tocopherols (alpha- and gamma-tocopherol) and carotenoids (alpha- and beta-carotene, zeaxanthin, cryptoxanthin, canthaxanthin, lycopene, and retinol). Plasma antioxidant concentrations were determined by HPLC in 7 patients with familial hypercholesterolemia before and after LDL immunoapheresis treatment. Plasma concentrations of both alpha- and gamma-tocopherol and the different carotenoids were significantly reduced by LDL apheresis. However, when standardized for cholesterol to adjust for cholesterol removal, alpha- and gamma-tocopherol, retinol, and the more polar carotenoids lutein and zeaxanthin increased in response to apheresis treatment, while the more unpolar carotenoids such as beta-carotene and lycopene did not change. These data demonstrate that a single LDL immunoapheresis treatment affects tocopherols and individual carotenoids differently. This may be explained by differences in chemical structure and preferential association with different lipoproteins. These results further imply that tocopherols, lutein, zeaxanthin, and retinol, are associated in part with lipoproteins and other carriers such as retinol-binding protein that are not removed during apheresis treatment.     

The stabilizing potential of anterior, posterior and combined techniques for the reconstruction of a 2-level cervical corpectomy model: biomechanical study and first results of ATPS prototyping

Clinical studies reported frequent failure with anterior instrumented multilevel cervical corpectomies. Hence, posterior augmentation was recommended but necessitates a second approach. Thus, an author group evaluated the feasibility, pull-out characteristics, and accuracy of anterior transpedicular screw (ATPS) fixation. Although first success with clinical application of ATPS has already been reported, no data exist on biomechanical characteristics of an ATPS-plate system enabling transpedicular end-level fixation in advanced instabilities. Therefore, we evaluated biomechanical qualities of an ATPS prototype C4–C7 for reduction of range of motion (ROM) and primary stability in a non-destructive setup among five constructs: anterior plate, posterior all-lateral mass screw construct, posterior construct with lateral mass screws C5 + C6 and end-level fixation using pedicle screws unilaterally or bilaterally, and a 360° construct. 12 human spines C3–T1 were divided into two groups. Four constructs were tested in group 1 and three in group 2; the ATPS prototypes were tested in both groups. Specimens were subjected to flexibility test in a spine motion tester at intact state and after 2-level corpectomy C5–C6 with subsequent reconstruction using a distractable cage and one of the osteosynthesis mentioned above. ROM in flexion–extension, axial rotation, and lateral bending was reported as normalized values. All instrumentations but the anterior plate showed significant reduction of ROM for all directions compared to the intact state. The 360° construct outperformed all others in terms of reducing ROM. While there were no significant differences between the 360° and posterior constructs in flexion–extension and lateral bending, the 360° constructs were significantly more stable in axial rotation. Concerning primary stability of ATPS prototypes, there were no significant differences compared to posterior-only constructs in flexion–extension and axial rotation. The 360° construct showed significant differences to the ATPS prototypes in flexion–extension, while no significant differences existed in axial rotation. But in lateral bending, the ATPS prototype and the anterior plate performed significantly worse than the posterior constructs. ATPS was shown to confer increased primary stability compared to the anterior plate in flexion–extension and axial rotation with the latter yielding significance. We showed that primary stability after 2-level corpectomy reconstruction using ATPS prototypes compared favorably to posterior systems and superior to anterior plates. From the biomechanical point, the 360° instrumentation was shown the most efficient for reconstruction of 2-level corpectomies. Further studies will elucidate whether fatigue testing will enhance the benefit of transpedicular anchorage with posterior constructs and ATPS.     

A biomechanical rationale for C1-ring osteosynthesis as treatment for displaced Jefferson burst fractures with incompetency of the transverse atlantal ligament

Nonsurgical treatment of Jefferson burst fractures (JBF) confers increased rates of C1–2 malunion with potential for cranial settling and neurologic sequels. Hence, fusion C1–2 was recognized as the superior treatment for displaced JBF, but sacrifies C1–2 motion. Ruf et al. introduced the C1-ring osteosynthesis (C1–RO). First results were favorable, but C1–RO was not without criticism due to the lack of clinical and biomechanical data serving evidence that C1–RO is safe in displaced JBF with proven rupture of the transverse atlantal ligament (TAL). Therefore, our objectives were to perform a biomechanical analysis of C1–RO for the treatment of displaced Jefferson burst fractures (JBF) with incompetency of the TAL. Five specimens C0–2 were subjected to loading with posteroanterior force transmission in an electromechanical testing machine (ETM). With the TAL left intact, loads were applied posteriorly via the C1–RO ramping from 10 to 100 N. Atlantoaxial subluxation was measured radiographically in terms of the anterior antlantodental interval (AADI) with an image intensifier placed surrounding the ETM. Load–displacement data were also recorded by the ETM. After testing the TAL-intact state, the atlas was osteotomized yielding for a JBF, the TAL and left lateral joint capsule were cut and the C1–RO was accomplished. The C1–RO was subjected to cyclic loading, ramping from 20 to 100 N to simulate post-surgery in vivo loading. Afterwards incremental loading (10–100 N) was repeated with subsequent increase in loads until failure occurred. Small differences (1–1.5 mm) existed between the radiographic AADI under incremental loading (10–100 N) with the TAL-intact as compared to the TAL-disrupted state. Significant differences existed for the beginning of loading (10 N, P = 0.02). Under physiological loads, the increase in the AADI within the incremental steps (10–100 N) was not significantly different between TAL-disrupted and TAL-intact state. Analysis of failure load (FL) testing showed no significant differences among the radiologically assessed displacement data (AADI) and that of the ETM (P = 0.5). FL was Ø297.5 ± 108.5 N (range 158.8–449.0 N). The related displacement assessed by the ETM was Ø5.8 ± 2.8 mm (range 2.3–7.9). All specimens succeeded a FL >150 N, four of them >250 N and three of them >300 N. In the TAL-disrupted state loads up to 100 N were transferred to C1, but the radiographic AADI did not exceed 5 mm in any specimen. In conclusion, reconstruction after displaced JBF with TAL and one capsule disrupted using a C1–RO involves imparting an axial tensile force to lift C0 into proper alignment to the C1–2 complex. Simultaneous compressive forces on the C1-lateral masses and occipital condyles allow for the recreation of the functional C0–2 ligamentous tension band and height. We demonstrated that under physiological loads, the C1–RO restores sufficient stability at C1–2 preventing significant translation. C1–RO might be a valid alternative for the treatment of displaced JBF in comparison to fusion of C1–2.     

A stable phage lysin (Cpl-1) dimer with increased antipneumococcal activity and decreased plasma clearance

Bacteriophages (phages) produce endolysins (lysins) as part of their lytic cycle in order to degrade the peptidoglycan layer of the infected bacteria for subsequent release of phage progeny. Because these enzymes maintain their lytic and lethal activity against Gram-positive bacteria when added extrinsically to the cells, they have been actively exploited as novel anti-infectives, sometimes termed enzybiotics. As with other relatively small peptides, one issue in their clinical development is their rapid inactivation through proteolytic degradation, immunological blockage and renal clearance. The antipneumococcal lysin Cpl-1 was shown to escape both proteolysis and immunological blockage. However, its short plasma half-life (20.5 min in mice) may represent a shortcoming for clinical usefulness. Here we report the construction of a Cpl-1 dimer with a view to increasing both the antipneumococcal specific activity and plasma half-life of Cpl-1. Dimerisation was achieved by introducing specific cysteine residues at the C-terminal end of the enzyme, thus favouring disulphide bonding. Compared with the native monomer, the constructed dimer demonstrated a two-fold increase in specific antipneumococcal activity and a ca. ten-fold decrease in plasma clearance. As several lysins are suspected to dimerise on contact with their cell wall substrate to be fully active, stable pre-dimerised enzymes may represent a more efficient alternative to the native monomer.     

Optimisation of multiple W/O/W nanoemulsions for dermal delivery of aciclovir

In the present study multiple W/O/W nanoemulsions were optimised for the dermal application of the antiviral drug aciclovir. The phase inversion temperature method was employed to prepare the formulations without the input of high pressure. During formulation design the ethoxylated surfactants were varied and if possible partly replaced by natural sugar surfactants. Multiple nanoemulsions with mean droplet sizes around 100 nm and polydispersity indices below 0.1 were prepared. At room temperature, they exhibited excellent physicochemical stability over an observation period of 6 months. Furthermore, cryo electron microscopy gave an insight into the microstructure of the multiple nanoemulsions. Moreover, the formulations' interaction with skin was analysed by ATR-FTIR. In Franz-type diffusion cell and tape stripping experiments aciclovir showed satisfying skin permeation from the novel nanoemulsions.