A new grading for easy and concise description of functional status after spinal cord lesions.

BACKGROUND: Disability scales do not enable the transmission of concise, meaningful and daily function description for clinical purposes. STUDY DESIGN: Cross-sectional statistical analysis of 328 patients' Spinal Cord Independence Measure (SCIM) III item scores (SIS). OBJECTIVE: To develop a concise and clinically interpretable data-based characterization of daily task accomplishment for patients with spinal cord lesions (SCLs). SETTING: Multi-center study at 13 spinal units in 6 countries. METHODS: Patients were grouped into clusters characterized by smaller differences between the patients' SIS within the clusters than between their centers, using the k-medoides algorithm. The number of clusters (k) was chosen according to the percent of SIS variation they explained and the clinical distinction between them. RESULTS: Analysis showed that k=8 SIS clusters offer a good description of the patient population. The eight functional clusters were designated as A-H, each cluster (grade) representing a combination of task accomplishments. Higher grades were usually (but not always) associated with patients implementing more difficult tasks. Throughout rehabilitation, the patients' functional grade improved and the distribution of patients with similar functional grades within the total SCIM III score deciles remained stable. CONCLUSIONS: A new classification based on SIS clusters enables a concise description of overall functioning and task accomplishment distribution in patients with SCL. A software tool is used to identify the patients' functional grade. Findings support the stability and utility of the grades for characterizing the patients' functional status.

Expected spinal cord independence measure, third version, scores for various neurological levels after complete spinal cord lesions.

STUDY DESIGN: Multicenter international cohort study. OBJECTIVE: The objective of this study was to establish target values for Spinal Cord Independence Measure (SCIM) III scoring in rehabilitation for clinically complete spinal cord lesion (SCL) neurological levels. SETTING: In total, 13 spinal cord units in six countries from North America, Europe and the Middle East were taken. METHODS: Total SCIM III scores and gain at discharge from rehabilitation were calculated for SCL levels in 128 patients with American Spinal Injury Association Impairment Scale (AIS) grade A on admission to rehabilitation. RESULTS: Median, quartiles, mean and s.d., values of discharge SCIM III scores and SCIM III gain for the various SCL levels are presented. Total SCIM III scores and gain were significantly correlated with the SCL level (r=0.730, r=0.579, P<0.001). CONCLUSIONS: Calculated discharge SCIM III scores can be used as target values for functional achievements at various neurological levels in patients after AIS A SCL. They are generally, but not always, inversely correlated with SCL level.

[Spectral domain OCT in patients with unclear uveitis]. / Spectral-domain-OCT bei unklarer Uveitis.

Presented here are two cases of patients with unclear visual loss. A diagnostic assessment with spectral domain optical coherence tomography (Sd-OCT), fluorescein angiography (FLA) and blood analyses was performed due to vitreous clouding. Characteristic FLA findings for papillitis and vasculitis and as yet undescribed morphological Sd-OCT changes in the photoreceptor layer and in the pigment epithelium were found. During the treatment of the diagnosed lues these changes were resolved. The Sd-OCT technique seems to be a useful and effective diagnostic tool for uveitis diagnostics.

[Worsening of vision with apparent changes of the posterior pole]. / Sehstörungen bei auffälligem Fundusbefund.

The choroidal osteoma is a typically unilateral, benign ossifying tumor of the choroid. It is mostly located in the juxtapapillary area and usually found in females in the second or third decade of life. Most patients are asymptomatic. However, some can present with blurred vision, metamorphopsia, and visual field defects. Ultrasonography can show a calcified choroidal plaque with a typical shadowing posterior to the lesion. Fluorescein angiography and optical coherence tomography should be used if choroidal neovascularization is suspected as a possible complication of the choroidal osteoma.

SCIM III is reliable and valid in a separate analysis for traumatic spinal cord lesions.

STUDY DESIGN: A multi-center international cohort study. OBJECTIVE: To evaluate the reliability and validity of the third version of the Spinal Cord Independence Measure (SCIM III), separately for patients with traumatic spinal cord lesions (SCLs). SETTING: A total of 13 spinal cord units in six countries from North America, Europe and the Middle-East. METHODS: SCIM III and Functional Independence Measure (FIM) were assessed for 261 patients with traumatic SCLs, on admission to rehabilitation and before discharge, by two raters. Conventional statistical measures were used to evaluate the SCIM III reliability and validity. RESULTS: In almost all SCIM III tasks, the total agreement between the paired raters was >80%. The κ coefficients were all >0.6 and statistically significant. Pearson's coefficients of the correlations between the paired raters were >0.9, the mean differences between raters were nonsignificant and the intraclass correlation coefficients (ICCs) were ≥ 0.95. Cronbach's α values for the entire SCIM III scale were 0.833-0.835. FIM and SCIM III total scores were correlated (r=0.84, P<0.001). SCIM III was more responsive to changes than FIM. In all subscales, SCIM III identified more changes in function than FIM, and in 3 of the 4 subscales, differences in responsiveness were statistically significant (P<0.02). CONCLUSION: The results confirm the reliability and validity of SCIM III for patients with traumatic SCLs in a number of countries.

[Anisocoria and nausea]. / Anisokorie und Ubelkeit.

We present the case of a 40-year-old female patient with sudden onset of anisocoria and unilateral ptosis of the left eye. With the exception of several previous episodes of nausea and vomiting, mild headache and tiredness, combined with the early death of the patient's mother following aortic rupture, patient history and clinical condition showed no pathological findings. Following indicative findings on duplex sonography, a dissection of the left internal carotid artery from its origin to its distal section was detected on CT angiography of the brain vessels and the diagnosis of Horner syndrome due to internal carotid artery dissection was made. Since this condition is associated with serious embolic complications, prompt treatment following diagnosis is of utmost importance. Our patient was treated conservatively using PTT (partial thromboplastin time)-effective heparinisation. Regular checks including kidney ultrasound, blood pressure measurement, imaging and continuous therapy with acetylsalicylic acid are recommended.

The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study.

PURPOSE: To examine the third version of the Spinal Cord Independence Measure (SCIM III) for reliability and validity in a multi-center cohort study. METHOD: Four hundred and twenty-five patients with spinal cord lesions from 13 spinal cord units in six countries from three continents were assessed with SCIM III and the Functional Independence measure (FIM) on admission to rehabilitation and before discharge. RESULTS: Total agreement between raters was above 80% in most SCIM III tasks, and all kappa coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.9, and intraclass correlation coefficients were above 0.94. Cronbach's alpha was above 0.7. The coefficient of Pearson correlation between FIM and SCIM III was 0.790 (P<0.01). SCIM III was more responsive to changes than FIM in the subscales of Respiration and sphincter management and Mobility indoors and outdoors. CONCLUSIONS: The results support the reliability and validity of SCIM III in a multi-cultural setup. Despite several limitations of the study, the results indicate that SCIM III is an efficient measure for functional assessment of SCL patients and can be safely used for clinical and research trials, including international multi-center studies.

A multicenter international study on the Spinal Cord Independence Measure, version III: Rasch psychometric validation.

BACKGROUND: A third version of the Spinal Cord Independence Measure (SCIM III), made up of three subscales, was formulated following comments by experts from several countries and Rasch analysis performed on the previous version. OBJECTIVE: To examine the validity, reliability, and usefulness of SCIM III using Rasch analysis. DESIGN: Multicenter cohort study. SETTING: Thirteen spinal cord units in six countries from North America, Europe, and the Middle-East. SUBJECTS: 425 patients with spinal cord lesions (SCL). INTERVENTIONS: SCIM III assessments by professional staff members. Rasch analysis of admission scores. MAIN OUTCOME MEASURES: SCIM III subscale match between the distribution of item difficulty grades and the patient ability measurements; reliability of patient ability measures; fit of data to Rasch model requirements; unidimensionality of each subscale; hierarchical ordering of categories within items; differential item functioning across classes of patients and across countries. RESULTS: Results supported the compatibility of the SCIM subscales with the stringent Rasch requirements. Average infit mean-square indices were 0.79-1.06; statistically distinct strata of abilities were 3 to 4; most thresholds between adjacent categories were properly ordered; item hierarchy was stable across most of the clinical subgroups and across countries. In a few items, however, misfit or category threshold disordering were found. CONCLUSIONS: The scores of each SCIM III subscale appear as a reliable and useful quantitative representation of a specific construct of independence after SCL. This justifies the use of SCIM in clinical research, including cross-cultural trials. The results also suggest that there is merit in further refining the scale.

Comments on the shortcomings of predicting the precision of Cavalieri volume estimates based upon assumed measurement functions.

It is well known that the estimation of an object's volume by means of serial cross-sections, the so-called Cavalieri method, yields an unbiased estimate. But by itself it provides no means by which to estimate how precise this estimate is unless the shape of the volume is fully known beforehand. This knowledge can only be partially determined from the serial section information that is collected. Methods have been developed that claim to surmount this difficulty by using the serial section data to create a mathematical model of the volume's shape properties. The model then is used to estimate (predict) the precision of the volume estimate (its CE) from the single set of data available. Unfortunately, the theory underlying the model is flawed and so the model itself amounts to no more than an unsubstantiated guess about the shape of the volume. Therefore, the precision of the volume estimates that one obtains from the method is only as good as the model and this cannot be ascertained from the single set of acquired data. In this letter I explain the inadequacies of the modelling method. I suggest that it be used only with caution, if at all. Instead I suggest two alternative ways to predict the CE, one that is based upon a rule-of-thumb approach to the object's shape, and another that is based upon spectral analysis of the measurement function and that is easy to implement with available computer software.

Mutagenesis and computer modelling approach to study determinants for recognition of signal peptides by the mitochondrial processing peptidase.

Determinants for the recognition of a mitochondrial presequence by the mitochondrial processing peptidase (MPP) have been investigated using mutagenesis and bioinformatics approaches. All plant mitochondrial presequences with a cleavage site that was confirmed by experimental studies can be grouped into three classes. Two major classes contain an arginine residue at position -2 or -3, and the third class does not have any conserved arginines. Sequence logos revealed loosely conserved cleavage motifs for the first two classes but no significant amino acid conservation for the third class. Investigation of processing determinants for a class III precursor, Nicotiana plumbaginifolia F1beta precursor of ATP synthase (pF1beta), was performed using a series of pF1beta presequence mutants and mutant presequence peptides derived from the C-terminal portion of the presequence. Replacement of -2 Gln by Arg inhibited processing, whereas replacement of either the most proximally located -5 Arg or -15 Arg by Leu had only a low inhibitory effect. The C-terminal portion of the pF1beta presequence forms a helix-turn-helix structure. Mutations disturbing or prolonging the helical element upstream of the cleavage site inhibited processing significantly. Structural models of potato MPP and the C-terminal pF1beta presequence peptide were built by homology modelling and empirical conformational energy search methods, respectively. Molecular docking of the pF1beta presequence peptide to the MPP model suggested binding of the peptide to the negatively charged binding cleft formed by the alpha-MPP and beta-MPP subunits in close proximity to the H111XXE114H115X(116-190)E191 proteolytic active site on beta-MPP. Our results show for the first time that the amino acid at the -2 position, even if not an arginine, as well as structural properties of the C-terminal portion of the presequence are important determinants for the processing of a class III precursor by MPP.

[Prevention of thromboembolism in spinal fractures with spinal cord injuries. Standard heparin versus low-molecular-weight heparin in acute paraplegia]. / Thromboembolieprophylaxe bei Wirbelsäulenfrakturen mit Rückenmarkverletzungen. Standard-Heparin versus niedermolekulares Heparin bei frischen Querschnittsyndromen.

In a prospective, randomized, open study, the therapeutic efficacy of a long-term prophylaxis with standard heparin (SH) was compared with that of low-molecular-weight heparin (LMWH) Dalteparin in 166 patients who had spinal fractures with spinal cord injury. 86 patients were treated with SH 2 x 7500 U s.c. and 80 patients were treated with LMWH 1 x 5000 anti-Xa U s.c. once daily. The screening was implemented by daily bedside-examination. In case of clinical thromboembolism-symptoms patients had confirmatory venography or lung scans. In the SH-group 12 (14.0%) patients had deep vein thrombosis and in the LMWH-group 6 (7.5%). Pulmonary embolism was detected two times in the SH-group (2.33%) and only one time in the LMWH-group (1.25%). A significant difference could not be shown, but is descriptive evident.

L and D presequence peptides derived from the precursor of F1beta subunit of the ATP synthase inhibit mitochondrial protein import by interaction with import machinery.

We investigated the effect of L and D enantiomers of a 25-residue peptide derived from the N-terminal region of the presequence of Nicotiana plumbaginifolia F1beta subunit of the ATP synthase, pF1beta(1, 25), on import into spinach leaf mitochondria. Three in vitro synthesized precursor proteins using different import pathways were used. Import of the precursor proteins of F1beta subunit of the ATP synthase, pre-F1beta, and the alternative oxidase, pre-AOX, required addition of external ATP. whereas the chimeric precursor containing the N-terminal 84 amino acids of the cytochrome b2 precursor protein linked to dihydrofolate reductase, pre-b2(1, 84)-DHFR was not dependent on ATP. Import of pre-F1beta, and pre-AOX was inhibited already at 1 microM and 3 microM concentration of the L and D enantiomers, whereas inhibition of import of pre-b2(1, 84)-DHFR, occurred at concentrations >10 microM of both enantiomers. Binding efficiency of the precursor proteins was not affected by addition of the L and D enantiomers. There was no correlation between inhibition of import of pre-F1beta and pre-AOX and dissipation of membrane potential measured as a decrease of Rhodamine 123 fluorescence quenching. The inhibitory effect of the L and D presequence enantiomers on import of pre-F1beta and pre-AOX was concluded to occur within the outer membrane translocase machinery beyond the initial precursor receptor interaction. Furthermore, the fact that the D enantiomer had the same effect as the natural peptide showed that interaction of the presequence with the import machinery was not dependent on chiral properties of the presequence.

Biomarker assays in nipple aspirate fluid.

The noninvasive technique of nipple aspiration as a potential source of biomarkers of breast cancer risk was evaluated. The feasibility of performing mutagenesis assays, amplifying DNA, and performing protein electrophoresis on nipple aspirate fluid was explored. A tool was developed to measure the level of discomfort, if any, from this procedure. Twenty-five healthy women (20 premenopausal and 5 postmenopausal) were enrolled. Fluid was obtained using a modified breast pump. Premenopausal women were scheduled for four to six weekly aspirations, and postmenopausal women were scheduled for one to two weekly aspirations. Mutagenesis assays were performed using the Salmonella (Ames) assay. DNA amplification of several microsatellite regions was carried out using polymerase chain reaction. Protein was quantified, and two-dimensional protein electrophoresis was performed. Overall, fluid was obtained from 80% of the women, and the level of discomfort was minimal. Acid hydrolysis of one sample resulted in mutagenicity; all six nonhydrolyzed samples were not mutagenic. The ability to amplify DNA ranged from 34% to 96%, depending on length of the microsatellite region examined. The average protein concentration was 71 microg/mL. Two-dimensional protein electrophoresis was successfully performed on samples from two subjects. Nipple aspiration is a simple technique and is easily learned and well tolerated, which yields a reagent useful for a variety of investigations. This technique may facilitate the identification and application of biomarkers for future breast cancer risk assessment and chemopreventive protocols.

Studies on the topology of the protein import channel in relation to the plant mitochondrial processing peptidase integrated into the cytochrome bc1 complex.

The mitochondrial processing peptidase (MPP) specifically cleaves N-terminal targeting signals from hundreds of nuclear-encoded, matrix-targeted precursor proteins. In contrast to yeast and mammals, the plant MPP is an integral component of the respiratory cytochrome bc1 complex. The topology of the protein import channel in relation to MPP/bc1 in plants was studied using chimeric precursors containing truncated cytochrome b2 (cyt b2) proteins of 55-167 residues in length, fused to dihydrofolate reductase (DHFR). The DHFR domain could be tightly folded by methotrexate (MTX), generating translocation intermediates trapped in the import channel with only the cyt b2 pre-sequence/mature domain protruding into the matrix. Spinach and soybean mitochondria imported and processed unfolded precursors. MTX-folded intermediates were not processed in spinach but the longest (1-167) MTX-folded cyt b2-DHFR construct was processed in soybean, while yeast mitochondria successfully processed even shorter MTX-folded constructs. The MTX-folded precursors were cleaved with high efficiency by purified spinach MPP/bc1 complex. We interpret these results as indicating that the protein import channel is located distantly from the MPP/bc1 complex in plants, and that there is no link between protein translocation and protein processing.

Stereology, morphometry, and mapping: the whole is greater than the sum of its parts.

The latest developments in computer-based stereology build upon the similarities of classical stereology and computer microscopy to provide refined and effective spatial analyses that also permit mapping of anatomical regions. Classical stereology and computer microscopy have developed along independent pathways as methodologies to provide a quantitative understanding of the structure of the brain. They approach brain morphology and brain morphometry from different points of view. On one hand, stereology has concentrated upon the unbiased numerical estimation of parameters, such as length, area, volume, and population size that characterize entire regions of the brain, e.g. hippocampus, as well as individual elements within them, e.g. cell volume. On the other hand, computer microscopy has concentrated upon providing accurate three-dimensional maps of the morphology of entire regions of the brain as well as of individual elements within them, e.g. neuronal dendrite and axon systems. The differences in point of view are not so extensive as to keep the two methodologies separate. They share, after all, a similar manner of controlling microscope data input and analyzing the images the microscope provides. The incorporation of data archiving permits easier access to previous studies, as well as the sharing of stereological findings and their related maps throughout the scientific community. Some of the stereological systems now integrate spatial mapping with stereological analyses to provide more comprehensive methods to analyze brain tissue.

Rapid degradation of the presequence of the f1beta precursor of the ATP synthase inside mitochondria.

We have investigated the fate of the presequence of an overexpressed protein derived from the precursor of the F(1)beta subunit of ATP synthase after import and processing in mitochondria. Our studies revealed a rapid degradation of the presequence inside mitochondria catalysed by matrix-located protease(s). In contrast, the mature portion of the precursor was not degraded. This is the first experimental evidence of the rapid degradation of a mitochondrial presequence in organello after in vitro import and processing.

[Malignant non-Hodgkin's lymphoma presenting with arrhythmia and conduction defects. Report of 2 cases]. / Troubles du rythme et de la conduction révélateurs d'une localisation cardiaque de lymphome malin non hodgkinien. A propos de 2 cas.

Primary cardiac lymphoma is very rare. Secondary localisations are more common, observed in 15 to 30% of autopsy series. Clinical symptoms of cardiac involvement are rare, explaining the usual post-mortem diagnosis. The presentation of cardiac involvement by arrhythmias and conduction defects is very uncommon. The authors report two cases, the first of a 35 year old man in whom primary cardiac lymphoma presented with ventricular tachycardia complicated secondarily by complete atrioventricular block (AVB) with pseudo-inferior wall infarction. The second case was a 37 year old man with a cutaneous T cell lymphoma in whom complete AVB was the first sign of a secondary cardiac localisation of his disease. The finding of cardiac lymphoma should lead to aggressive chemotherapy as soon as possible.

Integration of the mitochondrial-processing peptidase into the cytochrome bc1 complex in plants.

The plant mitochondrial cytochrome bc1 complex, like nonplant mitochondrial complexes, consists of cytochromes b and c1, the Rieske iron-sulfur protein, two Core proteins, and five low-molecular mass subunits. However, in contrast to nonplant sources, the two Core proteins are identical to subunits of the general mitochondrial processing peptidase (MPP). The MPP is a fascinating enzyme that catalyzes the specific cleavage of the diverse presequence peptides from hundreds of the nuclear-encoded mitochondrial precursor proteins that are synthesized in the cytosol and imported into the mitochondrion. Integration of the MPP into the bc1 complex renders the bc1 complex in plants bifunctional, being involved both in electron transport and in protein processing. Despite the integration of MPP into the bc1 complex, electron transfer as well as translocation of the precursor through the import channel are independent of the protein-processing activity. Recognition of the processing site by MPP occurs via the recognition of higher-order structural elements in combination with charge and cleavage-site properties. Elucidation of the three-dimensional (3-D) structure of the mammalian cytochrome bc1 complex is highly useful for understanding of the mechanism of action of MPP.