Virosome-based active immunization targets soluble amyloid species rather than plaques in a transgenic mouse model of Alzheimer’s disease

Active vaccination with amyloid peptides shows promise for the treatment and prevention of Alzheimer's disease (AD). Several studies in transgenic mouse models of AD have revealed the potency of vaccination to prevent or even clear amyloid plaques from mouse brain. However, the idea that soluble oligomeric species of beta-amyloid (Abeta), rather than plaques, trigger the disease has gained momentum, and current active vaccination strategies affect the levels of total or soluble brain Abeta little or not at all. We describe an active vaccination method based on Abeta1-16 presented on the surface of virosomes, which triggered a dramatic decrease in both soluble Abeta40 (75% reduction; p=0.01) and soluble Abeta42 (62% reduction; p=0.03) in a double transgenic mouse model of AD. Whereas Abeta40 and Abeta42 levels in the insoluble fraction tended to be reduced (by 30% and 27%, respectively), the number of thioflavine-S-positive amyloid plaques was not affected. The high specific antibody responses, obtained without eliciting T-cell reactivity, demonstrate that immunostimulating reconstituted influenza virosomes are a promising antigen carrier system against the neuropathology of AD.     

Sonography of a rupture of the tendon of the extensor pollicis longus muscle: initial clinical experience and correlation with findings at cadaveric dissection

OBJECTIVE: The objectives of our study were to report our initial clinical experience with sonography of the wrist for diagnosing a proximal rupture of the tendon of the extensor pollicis longus (EPL) muscle and to perform sonographic-anatomic correlation of the EPL tendon. MATERIALS AND METHODS: Clinical and imaging files of five patients who underwent sonography and subsequent open wrist surgery were reviewed retrospectively. Imaging was performed by four radiologists experienced in musculoskeletal sonography. Tendon retraction was evaluated on sonography and at surgery. In cadavers, sonography was performed in concert by two musculoskeletal radiologists during progressive stages of dissection of four embalmed specimens. One specimen was sliced in the transverse plane. RESULTS: In cadavers, the EPL tendon was located on or adjacent to Lister's tubercle and extended to the base of the thumb. The EPL tendon crossed over the extensor carpi radialis tendons where it exhibited a flattened aspect. In the five patients in the study, a tubular-shaped hypoechoic area was evident at the position of the ruptured EPL tendon on sonograms. At surgery, this area corresponded to fluid, hemorrhage, and scar tissue in the EPL tendon sheath. The assessment of tendon retraction on sonography correlated with findings at surgery. CONCLUSION: Sonography may aid in diagnosing a rupture of the EPL tendon and in the preoperative assessment of gap size and position of the retracted tendon ends. A characteristic tubular hypoechoic area may be seen crossing over the extensor carpi radialis tendons.     

Speech recognition with a cochlear implant using triphasic charge-balanced pulses

OBJECTIVE: Typically, symmetrical charge-balanced biphasic current pulses are used in cochlear implants to ensure biological safety. Theoretically, monophasic pulses are more effective, but potentially noxious, stimuli. In this study we charge-balanced such monophasic pulses during selected non-stimulated intervals, effectively leading to triphasic pulses with a 4:1 amplitude ratio between the cathodic and anodic phases. Apart from ensuring safety, this is also expected to reduce power consumption and channel interaction. MATERIAL AND METHODS: Seven experienced Clarion CII cochlear implant users with a multichannel (12-16 channels) monopolar continuous interleaved sampling (CIS) strategy participated in the study. Three different CIS strategies were fitted using the Clarion Research Interface (CRI-2). The reference was an implementation of each subject's own CIS program. The two strategies tested used triphasic pulses on the same channels, one with half-wave rectification (TP-HWR) and one without rectification (TP-NoR) at the input. Directly after fitting (i.e. without any training), speech perception (phoneme score on consonant-vowel-consonant words) was measured in silence (sound-only) and in speech-shaped background noise with signal:noise ratios (SNRs) of +5 and 0 dB. RESULTS: Speech perception with the reference via the CRI-2 was equal to that of the free-field condition with the subjects' own speech processor. With the TP-NoR strategy, speech perception improved significantly (from 89% to 93%) in silence and in the 0-dB SNR condition (from 43% to 49%). With a SNR of +5 dB, performance was stable at approximately 66%. With the TP-HWR strategy, performance increased significantly in the 0- and +5-dB SNR conditions, to 55% and 74%, respectively. Power consumption was reduced in both strategies, to 30% and 36% for TP-HWR and TP-NoR, respectively. CONCLUSION: The new triphasic strategies are most promising, with respect to both their improved speech perception and reduced power requirements. The optimal parameters will have to be identified following long-term use.     

Treatment of a metastasis of a rectal carcinoma in the greater trochanter with the AO/ASIF Proximal Femoral Nail. A case report

A 48-year-old patient was referred to our department because of a solitary metastasis of a rectal carcinoma, localized in the left greater trochanter. Since the risk of pathological fracture was higher than acceptable for radiation therapy alone and because of the young age of the patient, radical debulking and reconstruction using the AO/ASIF Proximal Femoral Nail and cement augmentation was performed. Solitary bone metastases of colorectal adenocarcinomata are rare, as discussed. The prognosis of a primary colorectal carcinoma in the presence of a bone metastasis, even a solitary one, is poor. In patients with these metastases with poor overall prognosis, the treatment objectives, which we could define as 'safe, short and simple' are stringent, although there most certainly remains an indication for palliative surgery.     

Occult fracture of the trapezoid bone: a report on two cases

The authors report two cases of isolated, undisplaced, fractures of the trapezoid bone. Because of its well-protected position in the wrist, traumatic lesions of the trapezoid bone are rare. Dislocation of the trapezoid has been reported in 30 patients; fractures are seen even less frequently and usually go with dorsal displacement. To our knowledge and based on a Medline literature review, only two cases of acute and isolated, undisplaced or minimally displaced fractures of the trapezoid have been previously described. We believe that the lesion has often been missed in the past and modern diagnostic tools will make its diagnosis far more frequent.     

Factors determining the final outcome of treatment of idiopathic scoliosis with the Boston brace: a longitudinal study

This study tries to determine factors influencing the final outcome of treatment of idiopathic scoliosis with the Boston brace and to compare the results with the natural history. One hundred and fifty-one patients, 130 girls and 21 boys, treated between 1982 and 1991, were reviewed. A series of continuous and categorical variables were measured, allowing for the construction of a multiple regression equation. Continuous variables were age at discovery of the curve, time of interval between discovery and treatment and age at the beginning of treatment. Furthermore age of menarche, duration of treatment, duration of weaning and age and time of follow-up were noted. Continuous numerical variables were the Cobb angle, the apical vertebral rotation, and the Risser stage. Categorical variables consisted of the results of a questionnaire and the King's classification of the curve. Good results are achieved in older children, with low Cobb angles and advanced maturity, who are, however, the very ones not expected to progress, as also indicated in studies on natural history. Brace treatment seems not to alter the natural history in general, and especially not in the older child; this is the case from age 12 years and Risser stage 2 onwards. In the younger child, a brace is probably still indicated, because it has been proved that a scoliosis is more prone to progress and that a possible positive result can still not be ruled out, as long as randomized control trials are not conducted.     

Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability

BACKGROUND AND PURPOSE: Patients who experience pain, a symptom of chronic fatigue syndrome (CFS), often exhibit kinesiophobia (irrational fear of movement). The purpose of this study was to examine whether pain-related fear of movement is associated with exercise capacity, activity limitations, or participation restrictions in patients with CFS who experience widespread pain. SUBJECTS AND METHODS: Sixty-four subjects met the inclusion criteria. All subjects fulfilled the 1994 Centers for Disease Control and Prevention case definition for CFS and experienced widespread myalgias or arthralgias. The subjects completed the Tampa Scale for Kinesiophobia-Dutch Version (TSK-DV) and the Dutch Chronic Fatigue Syndrome-Activities and Participation Questionnaire (CFS-APQ). They then performed a maximal exercise test on a bicycle ergometer. Heart rate was monitored continuously by use of an electrocardiograph. Ventilatory factors were measured through spirometry. Correlations between the TSK-DV scores and both the exercise capacity data and the CFS-APQ scores were assessed using the Spearman rank correlation coefficient. Using the Mann-Whitney U test, the TSK-DV scores were compared between subjects who performed a maximal exercise stress test and those who did not perform the test. RESULTS: Forty-seven subjects (73.4%) attained a total score of greater than 37 on the TSK-DV, indicating high fear of movement. Neither the exercise capacity data nor the CFS-APQ scores indicated a correlation with the TSK-DV scores (n=64). Subjects who did not perform a maximal exercise capacity test had more fear of movement (median TSK-DV score=43.0, interquartile range=10.3) compared with those who did perform a maximal exercise capacity test (median TSK-DV score=38.0, interquartile range=13.2; Mann-Whitney U-test score=322.5, z=-1.974, P=.048), but the correlation analysis was unable to reveal an association between exercise capacity and kinesiophobia in either subgroup. DISCUSSION AND CONCLUSION: These results indicate a lack of correlation between kinesiophobia and exercise capacity, activity limitations, or participation restrictions, at least in patients with CFS who are experiencing widespread muscle or joint pain.     

Treatment of a Humeral Metastasis with a Composite Allograft-Prosthetic Reconstruction

Abstract Background: The treatment of impending pathological fractures and symptomatic metastases involving the upper extremity articulations remains a challenge for the trauma surgeon. While the goals of treatment of bony metastases are clearly defined (early restoration of function, excellent pain control and minimal surgical trauma), these are not always easy to realize in upper extremity periarticular metastases. Case Study: A patient with a metastasis of a mediastinal nerve sheet tumor, involving the proximal 12 cm of the right humerus, including the whole head and both the tubercles, is described. A complete resection up to the level of the deltoid insertion was performed. In order to restore maximal function, the shoulder joint was reconstructed using a reversed total shoulder prosthesis. A fresh frozen cadaver proximal humerus was used as an allograft to obtain a secure stabilization of the prosthesis. Short-term results were very promising with restoration of ADL (activities of daily living) functionality within 3 months. Abduction and elevation > 100°, exorotation up to 20° and gluteal endorotation could be performed at that time. Conclusion: To the authors knowledge, this report is the first to describe reconstruction of the shoulder joint using a reversed shoulder prosthesis-allograft construction in case of a resection for malignancy.     

Does hip strength analysis explain the lower incidence of hip fracture in the People's Republic of China?

To explore whether there are ethnic differences in calculated hip strength that might explain the low incidence of hip fracture in China, we used Lunar DPX 'beta' version of hip strength analysis (HAS) and hip axis length (HAL) programs to compare hip geometry, calculated strength and densitometric values from Chinese subjects in Shenyang to those of Caucasian subjects in Oslo and Leuven participating in the European Prospective Osteoporosis Study (EPOS). Subjects were 210 Chinese and 403 Caucasian men and women aged 53-77 years. Parameters investigated included bone mineral density (BMD), bone mineral content (BMC), bone area (BA), cross-sectional moment of inertia (CSMI) and section modulus (both indicating strength and rigidity of the femoral neck), HAL, neck length (NL), neck diameter, tensile stress (Tstress) and compressive stress (Cstress) (indicating the stress in the femoral neck at its weakest cross section arising from walking or a standard fall, respectively), safety factor (SF, indicating the resistance to fracture for forces generated during walking) and fall index (FI, indicating the resistance to fracture from force generated during a fall in the greater trochanter). The Chinese men and women were significantly shorter and lighter than their Caucasian counterparts (P<0.01) and had significantly lower BMD, BMC and BA of the femoral neck (P<0.01). After adjusting for BA, weight and height, there was no significant ethnic difference in either gender in BMC. CSMI and section modulus were significantly lower, and HAL, NL and neck diameter were significantly shorter in the Chinese men and women (P<0.01). These differences all remained after adjusting for weight and height. There were no significant differences in Tstress, Cstress, SF and FI between ethnic groups in either gender. Most of the parameters of calculated hip strength in the Chinese subjects were similar to or poorer than those in the Caucasian subjects. There was no evidence to indicate that Shenyang Chinese have superior BMD or BMC or better calculated hip strength. The short HAL and NL of the population, however, could be an independent factor contributing to the low incidence of hip fracture.