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.

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.

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.

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 new electrogenic step in the ubiquinol:cytochrome c2 oxidoreductase complex of Rhodopseudomonas sphaeroides.

Myxothiazol, an inhibitor of the ubiquinol oxidase site of the ubiquinol:cytochrome c2 oxidoreductase complex, has been shown in the present work to inhibit a part of the electrogenic process indicated by phase III of the carotenoid change, in addition to the part of the change inhibited by antimycin. This finding shows that there is an antimycin-insensitive, but myxothiazol-sensitive portion of the slow phase, which indicates the existence of an electrogenic event within the ubiquinol:cytochrome c2 oxidoreductase complex, in addition to that linked to oxidation of cytochrome b-561 which has been previously characterized. Redox titrations show that the appearance of the new electrogenic step is correlated with the amount of cytochrome b-561 available in the oxidized form before the flash. The rate of the antimycin-insensitive and myxothiazol-sensitive portion of the carotenoid change correlates well with the rate of reduction of cytochrome b-561. No carotenoid change associated with reduction of cytochrome b-566 was seen. These findings suggest that the newly identified electrogenic process is linked to electron transfer between cytochrome b-566 and b-561. Calculations of the contribution of this new electrogenic step to the total electrogenic event within the complex show that electrons passing from cytochrome b-566 to cytochrome b-561 pass about 35-50% of the distance across the whole membrane.

Nutrition and somatomedin. XVII. Circulating somatomedin C during treatment of diabetic ketoacidosis.

Although somatomedin levels may be low in animals with experimental diabetes, values in humans have generally been normal. Because humans with severely decompensated diabetes have not been studied, we characterized somatomedin C responses during metabolic restoration in 21 patients with diabetic ketoacidosis. Somatomedin C values were compared with those of 25 outpatient controls. Somatomedin C in controls (mean +/- SE) was 0.72 +/- 0.09 U/ml, 69% of the mean sex-adjusted normal level; 28% of patients had values below the lower limit of normal. In ketoacidotic subjects, initial somatomedin C was 0.43 +/- .06 U/ml, 33% of the mean normal level; 52% of subjects had somatomedin C below the lower limit of normal. Initial levels in ketoacidotic subjects were unrelated to presenting levels of glucose, bicarbonate, ketones, or blood urea nitrogen but were significantly lower in patients of less than ideal body weight (0.30 vs. 0.58 U/ml, P less than .03). Presenting levels of somatomedin C in ketoacidotic subjects were significantly lower than in controls (P less than .02). During insulin-infusion therapy, somatomedin C rose to a peak of 1.16 +/- 0.21 U/ml after 28 h, significantly higher than initial levels (P less than .05). With continued subcutaneous insulin, somatomedin C fell to a nadir after an additional 22 h then rose more slowly to a final value of 0.75 +/- 0.12 U/ml, significantly higher than the nadir (P less than .05) but lower than peak values; final values in the ketoacidotic subjects were comparable to outpatient somatomedin C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of mitochondrial presequences with DnaK and mitochondrial hsp70.

Mitochondrial heat shock protein 70 (mt-hsp70) functions as a molecular chaperone in mitochondrial biogenesis. The chaperone in co-operation with its co-proteins acts as a translocation motor pulling the mitochondrial precursor into the matrix. Mt-hsp70s are highly conserved when compared to the bacterial hsp70 homologue, DnaK. Here we have used DnaK as a model to study the interaction of mitochondrial presequences with mt-hsp70 applying a DnaK-binding algorithm, computer modeling and biochemical investigations. DnaK-binding motifs have been analysed on all available, statistically relevant mitochondrial presequences found in the OWL database by running the algorithm. A total of 87 % of mammalian, 97 % of plant, 71 % of yeast and 100 % of Neurospora crassa presequences had at least one DnaK binding site. Based on the prediction, five 13-mer presequence peptides have been synthesized and their inhibitory effect on the molecular chaperone (DnaK/DnaJ/GrpE) assisted refolding of luciferase has been analysed. The peptide with the highest predicted binding likelihood showed the strongest inhibitory effect, whereas the peptide with no predicted binding capacity showed no inhibitory effect. A 3D structure of the pea mt-hsp70 has been constructed using homology modeling. The binding affinities of the 13-mer presequence peptides and additional control peptides to DnaK and pea mt-hsp70 have been theoretically estimated by calculating the buried hydrophobic surface area of the peptides docked to DnaK and to the mt-hsp70 structural model. These results suggest that mitochondrial presequences interact with the mt-hsp70 during or after mitochondrial protein import.

Cross-reconstitution of isolated F1-ATPase from potato tuber mitochondria with F1-depleted beef heart and yeast submitochondrial particles.

Cross-reconstitution of isolated potato mitochondrial F1-ATPase with F1-depleted beef heart and yeast submitochondrial particles is reported. Potato F1 binds to the heterologous membrane and confers oligomycin sensitivity on the ATPase activity of the reconstituted system. Binding of F1 is promoted by the presence of Mg2+ with the maximal stimulatory effect at 20 mM. Mg2+ increase the sensitivity to oligomycin of the reconstituted system consisting of potato F1 and yeast membranes, however, they do not influence oligomycin sensitivity of potato F1 and beef heart membranes.

Bifunctional role of the bc1 complex in plants. Mitochondrial bc1 complex catalyses both electron transport and protein processing.

Nuclear encoded mitochondrial precursor proteins are cleaved to mature size products by the general mitochondrial processing peptidase (MPP). In contrast to non-plant sources where MPP is a matrix enzyme, the plant mitochondrial MPP is localised in the inner membrane and constitutes an integral part of the bc1 complex of the respiratory chain. Core proteins of the complex are immunologically related and show high sequence similarity to the MPP subunits from non-plant sources. The bc1 complex in plants is thus bifunctional, being involved both in respiration and in protein processing.

Reduction of cytochrome b-561 through the antimycin-sensitive site of the ubiquinol-cytochrome c2 oxidoreductase complex of Rhodopseudomonas sphaeroides.

Cytochrome b-561 of the ubiquinol-cytochrome c2 oxidoreductase complex of Rhodopseudomonas sphaeroides is reduced after flash illumination in the presence of myxothiazol in an antimycin-sensitive reaction. Flash-induced reduction was observed over the redox range in which cytochrome b-561 and the Q-pool are both oxidized before the flash. The extent of reduction increased with increasing pH, and was maximal at pH greater than 10.0 where the extent approached that observed in the presence of antimycin following a group of flashes. Reduction of cytochrome b-561 in the presence of myxothiazol showed a lag of approximately 1 ms after the flash, followed by reduction with t 1/2 approximately 6 ms; by analogy with the similar kinetics of the quinol oxidase site, we suggest that the rate is determined by collision with the QH2 produced in the pool on flash excitation.

Morphology and laminar distribution of nonpyramidal neurons in the auditory cortex of the rabbit.

A study of the morphology and laminar distribution of nonpyramidal neurons in Golgi-Nissl preparations of electrophysiologically verified auditory cortex was carried out in the adult rabbit. Nonpyramidal neurons were located primarily within laminae I-IV and were only infrequently seen in lamina V and VI. In lamina I, four nonpyramidal cell types were observed: (1) small, spine-free horizontal neurons, (2) small, sparsely spined multipolar neurons with radiate dendrites, (3) large, multipolar neurons with fusiform somata and vertically aligned, sparsely spined dendrites, and (4) small, spine-free neurogliform neurons. The horizontal and small multipolar neurons had tangentially running axons confined to lamina I. The large, fusiform cells had descending axons which arborized in lamina II and occasionally reached lamina III. In lamina II and the upper part of lamina III, seven nonpyramidal cell types were observed: (1) spine-free bipolar neurons with vertically aligned dendrites and axonal arbors; (2) large, (3) medium, and (4) small, spine-free and sparsely spined multipolar neurons, all with locally ramifying axons; (5) pear-shaped cells with highly oriented dendrites which branched toward the pial surface and vertically arborizing axons; (6) multipolar cells with tangentially and vertically oriented dendrites and ascending axons which entered lamina I, and (7) tufted cells with local axons. Three types of nonpyramidal cells were observed in lamina IV and the lower part of lamina III: (1) large, multipolar cells with radiate, spine-free dendrites and stout axons which arborized locally, (2) spiny multipolar cells with vertically aligned dendrites and ascending axons which arborized in lamina II and III via long horizontal collaterals, and (3) spine-free bipolar cells with vertical dendrites and axons which arborized in a narrow vertical column adjacent to the dendrites. Nonpyramidal neurons in lamina V and VI were primarily multipolar cells with sparsely spined and spine-free dendrites. A comparison of these data with those of other species indicates that the neuronal organization of the rabbit auditory cortex is similar to that of the sensory cortex of the rodent but is strikingly different from that of carnivores and primates.

Postnatal development of lamina III/IV nonpyramidal neurons in rabbit auditory cortex: quantitative and spatial analyses of Golgi-impregnated material.

We have studied the postnatal development of lamina III/IV spine-free nonpyramidal neurons in the auditory cortex of the New Zealand white rabbit. The morphology and dendritic branching pattern of single cells impregnated with a Golgi-Cox variant were analyzed with the aid of camera lucida drawings and three-dimensional reconstructions obtained with a computer microscope. Sample sizes of 20 neurons were obtained at birth (day 0), postnatal day (PD) 3, 6, 9, 12, 15, 21, and 30 days of age. Normative data were also available from PD-60 and young adult rabbits studied previously. At birth, lamina II-IV have not yet emerged from the cortical plate; immature nonpyramidal neurons at the bottom of the cortical plate (presumptive layer IV) are characterized by short, vertically oriented dendrites. Growth-cone-like structures are present along the shafts and at the tips of the dendrites. At birth, soma area and total dendritic length are, respectively, 34 and 10% of adult values. The cortical plate acquires a trilaminar appearance at PD-3. The six-layered cortex is present by PD-6. During the first postnatal week dendritic length increases fourfold and is accompanied by a significant increase in both terminal and preterminal dendritic growth cones. At the onset of hearing at PD-6, there is a significant proliferation of dendrites and branches to 144 and 200% of adult levels, respectively. These supernumerary dendrites are rapidly lost during the second postnatal week, at which time the somata and dendrites become covered with spines. The loss of higher-order dendrites occurs more gradually; the number of dendritic branches is still 116% of adult values at PD-30. Spine density peaks between days PD-12 and PD-15, and then gradually diminishes until the cells are sparsely spined or spine free by PD-30. Total dendritic length increases in a linear fashion up to PD-15, at which time it is 80% of adult values. An analysis of terminal and intermediate branches demonstrated that the increase in total dendritic length after PD-6 is due entirely to the growth of terminal dendrites. Total dendritic length attains adult levels by PD-30. Spatial analyses revealed that a vertical orientation of dendrites is present at birth. Associated with the onset of hearing at PD-6, there is an explosive elaboration of dendrites toward the pial surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Morphometry of spine-free nonpyramidal neurons in rabbit auditory cortex.

A study of the morphometry and laminar distribution of spine-free nonpyramidal neurons in electrophysiologically verified primary auditory cortex was carried out in adult rabbits. By using image-combining computer microscopy, the locations of all impregnated neurons in 300-micrometers Golgi-Cox Nissl sections through the auditory cortex were determined. Spine-free non-pyramidal neurons constitute nearly 72% of the nonpyramidal neurons present. They are distributed in a band extending from 450 to 750 micrometers beneath the pial surface corresponding to laminae III and IV. A combination of dendritic stick, Fourier, and statistical analyses revealed a highly significant spatial orientation of their dendrite systems along a vertical axis parallel to the apical dendrites of pyramidal neurons. A significant tangential orientation of dendrites along a dorsal-ventral axis was also found. A radial analysis of the dendrite systems revealed that the pronounced vertical orientation of spine-free nonpyramidal neurons is due to (1) directed dendritic growth along the vertical axis, (2) decreased branching and rapid termination of tangentially oriented dendrites, and (3) increased branching of vertically growing dendrites. The radial analysis also revealed that the longest branches are those directed toward the white matter.

Neonatal deafening alters nonpyramidal dendrite orientation in auditory cortex: a computer microscope study in the rabbit.

In order to examine the influence of afferent input on nonpyramidal dendrite development in the auditory cortex, unilateral deafening was carried out in neonatal rabbits at birth, approximately 6 days prior to the onset of hearing. Deafening was produced by surgical removal of the incus and stapes ossicles, aspiration of the cochlear perilymph, and kanamycin injection into the oval window. At 60 days of age, acoustic stimulation of the deafened ear was unable to evoke auditory brainstem responses. The brains of experimental and littermate control rabbits were processed according to the Golgi-Cox Nissl method. The dendritic systems of lamina III/IV spine-free nonpyramidal cells in the auditory cortex contralateral to the deafened ear were digitized from 340-micron-thick coronal sections with the aid of a computer microscope. Three-dimensional spatial and statistical analyses revealed that nonpyramidal dendrite length in neonatally deafened rabbits increased 27% relative to littermate controls. A fan-in projection analysis revealed that the increased dendrite length in the deafened animals was maximum in the tangential direction and toward the white matter. Computer rotation of digitized neurons from neonatally deafened rabbits also revealed evidence of abnormal dendritic growth in the form of recurved dendrites. We interpret our results to indicate that unilateral cochlear destruction early in development causes a reorganization of the ascending auditory pathway which extends to the contralateral cerebral cortex. Because the auditory cortex contralateral to the deafened ear still receives acoustic input from the undamaged ipsilateral ear, normal nonpyramidal dendritic growth in the auditory cortex is, in part, dependent upon afferent activity arising from both ears.

Use of outpatient clinics as a health indicator for communities around a coal-fired power plant.

The permit to operate the first coal fired power plant in Israel was issued with the condition that a comprehensive network to monitor its effects on the environment, health, and agriculture must be installed and operated around the plant. The health monitoring system consists of four studies, which started 1 year prior to the operation of the plant and were carried out for 10 years. In the framework of the health monitoring system, a study of requests for health services was carried out. In this survey, 8 clinics of the Sick Fund, served by 16 physicians, were followed up. The clinics were located as near as possible to air pollution monitoring stations and represent expected different levels of pollution. A health recorder summarized each day's visits to each physician and tabulated the total visits for each day and the visits due to respiratory tract complaints. Multivariate stepwise regressions on total as well as on respiratory complaints were carried out. The independent variables in the regressions were sulfur dioxide, meteorological parameters (such as temperature and humidity), and flu epidemics. Temperature was almost always significantly correlated with respiratory complaints, but less correlated with total visits among, adults and children. Sulfur dioxide, most meterological parameters and flu epidemics were not meaningful explanatory factor in the regressions. Ambient air pollution levels did not exceed the Israeli air quality or the more stringent local air quality standards, the monthly and annual average sulfur dioxide and nitrogen oxides values were very low.

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.

The fan-in projection method for analyzing dendrite and axon systems.

The fan-in projection is a computer graphical method of projecting onto a half plane the branching patterns of dendrites and axons that have already been 3-dimensionally digitized. It is suited for neurons possessing an axis of orientation (or elongation), such as cortical neurons. This axis is taken as the polar axis of a spherical coordinate system whose center is the soma. For cortical neurons, the equatorial plane corresponds to the tangential plane. Co-latitude is measured with respect to the positive polar axis. Longitude is discarded. What results is a projection in which dendrites and axons appear to be growing in a half plane whose boundary is the polar axis. The projection eliminates many of the distorting effects of depth foreshortening seen in conventional projections. In so doing it helps one to visualize branching properties that would otherwise be obscure.

Analysis of thick brain sections by obverse-reverse computer microscopy: application of a new, high clarity Golgi-Nissl stain.

Exceptionally clear Golgi-Nissl sections of 300 micron thickness have been morphometrically studied by light microscopy using oil immersion objectives. The clarity results from a new variation of a staining procedure that combines Golgi and Nissl images in one section. A viewing technique has been developed that permits a histologic preparation to be examined from its obverse (or normally viewed) side and its reverse (or under) side. The technique was designed for use with a computer microscope but can be employed with any light microscope whose stage position can be measured within 100 micron. Sections thicker than 300 micron can be studied dependent on the working distance of the objective lens, provided that the clarity of the material permits it.