Central motor conduction times using transcranial stimulation and F wave latencies

The purpose of this study was to determine central motor conduction times between the motor cortex and the C8 spinal cord level (MC/C8), the motor cortex and S1 cord level (MC/S1), and C8 and S1 (C8/S1). We stimulated 29 normal subjects with a transcranial high voltage (300-500 V), short duration spike waveform (time constant 50 mu sec) and recorded over the hypothenar or calf muscles. F wave and M response latencies were used to estimate peripheral conduction time. The mean MC/C8 conduction time was 4.4 +/- 0.6 msec. Out of 26 subjects tested, 14 had discernable responses in the calf. The mean MC/S1 conduction time was 13.1 +/- 2.5 msec, and the mean estimated C8/S1 conduction time was 8.5 +/- 2.3 msec. This technique accurately measures conduction time from the motor cortex to the cervical anterior horn cells but is less reliable for monitoring conduction to the sacral cord. These values will facilitate future studies in patients with suspected lesions of the descending motor pathways.     

Quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow and local cerebral glucose utilization using 14C-IAP and 18F-FDG

We have reported a quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using 14C-IAP and 18F-FDG respectively. Six awake normal rats and 3 left middle cerebral artery (MCA) occluded rats were used for this experiments. A 50-hold greater radioactivity of 18F was administered and the first exposure was done for 2 hours to obtain a 18F image. Three days later (39 half-lives of 18F), a second exposure was done for 5 to 6 days to obtain the 14C image. Tissue concentration of 14C was measured relative to the commercially available 14C-methyl methacrylate standards. 18F standards were prepared in each experiment. Cross contamination of 14C in the first exposure was less than 2% in the normal state and less than 4% even in the uncoupling condition. The values obtained by this methods for LCBF and LCGU agreed closely with those obtained by a single tracer technique previously reported in the literature. The technique outlined in this paper also provided local glucose utilization flow ratio (LGFR) for the first time. LGFR was obtained by dividing the LCGU image by LCBF image and was expressed as percent mumol/ml. The mean LGFR of control rats was 76 +/- 8% mumol/ml. In a MCA occlusion group, LGFR of ischemic cortex increased until 2 to 3 times higher than that of contralateral non-ischemic cortex. Oxygen glucose index image which was obtained from the LCGU and A-V differences of O2 showed that approximately half of the glucose was metabolized anerobically.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factor XII, plasma prekallikrein, alpha 2-macroglobulin and C1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A--sequential measurements over four months in 17 patients

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), alpha 2-Macroglobulin (alpha 2-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 +/- 27% and 102 +/- 21%, respectively, mean +/- S.D.) and alpha 2-M and C1-Inh levels were slightly elevated (115 +/- 55% and 129 +/- 32%, respectively, mean +/- S.D.). In the first two weeks after transplantation a significant decrease of F XII to 65 +/- 27%, of PK to 67 +/- 20% and of alpha 2-M to 88 +/- 42%, and a rise of C1-Inh to 201 +/- 44% (mean +/- S.D.) were observed (2 p less than 0.005). F XII levels four month after operation remained significantly (2 p less than 0.05) lower than preoperatively. PK and alpha 2-M values, however, were significantly higher (2 p less than 0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, alpha 2-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and alpha 2-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p less than 0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, alpha 2-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.     

Morphometry of GFA and vimentin positive astrocytes in grafted and lesioned cortex cerebri

The presence and morphology of GFA- and vimentin-positive astrocytes were studied immunohistochemically in rats using smear preparations of single intraocular grafts of the cortex cerebri anlage and of cortex pieces grafted to eyes containing a previously grafted piece of the locus coeruleus area. Similarly, astrocytes were studied in lesioned cortex cerebri in situ. A high number of GFA and vimentin-positive cells were found in smears of both types of cortex grafts as well as in smears of the lesioned cortex cerebri in situ. In contrast, only a limited number of GFA-positive astrocytes were seen in smears of normal cortex. Using computerized image analysis, the two-dimensional cell area and cell perimeter were found to be significantly increased in individual GFA-positive astrocytes in both types of intraocular cortex grafts as well as in the lesioned cortex when compared to GFA-positive astrocytes in normal cortex cerebri.GFA-positive cells in smears of cortex grafts from locus coeruleus-cortex combinations had significantly smaller cell area and cell perimeter values compared to similar cells from single cortex grafts. A similar, although less pronounced difference was observed between vimentin-positive cells from the same type of grafts. This suggests that the presence of the mature locus coeruleus graft in some as yet unknown way influences the development of the adjacent cortex graft towards a more normal astrocytic maturation. An additional finding was the large size difference between GFA- and vimentin-positive cells in the intraocular grafts. Since most evidence indicates that vimentin-positive cells are also GFA-positive, this may indicate that the two intermediate filament systems have a partially different distribution within individual astrocytes.It is concluded that computerized image analysis of smears processed for immunohistochemistry with antisera against GFA and vimentin is a useful technique for studies of astrocyte morphology in normal as well as experimentally perturbed CNS tissue. Cortex tissue that develops in contact with a locus coeruleus graft in the eye chamber show a significantly lesser degree of gliosis than cortex tissue developing in isolation in the eye.     

Quantitative evaluation of tongue atrophy on midsagittal magnetic resonance images (MRIs)]

This study was undertaken mainly to establish the quantitative parameter to evaluate the tongue atrophy on midsagittal MRIs and to show the clinical usefulness of such quantitative evaluation. Midsagittal MRIs of the tongue of consecutive 103 patients were analyzed. They were classified into 67 patients showing normal size (group without atrophy), 11 patients showing atrophy (group with atrophy) and 25 patients showing unsatisfactory MRIs with artefacts based on the routine evaluation. The patients in the group without atrophy did not show any pathologic processes to produce tongue atrophy on clinical findings. The area and perimeter of tongue and oral cavity, and the ratio of tongue area to oral cavity area and the ratio of tongue perimeter to oral cavity perimeter on midsagittal MRIs were obtained in each patient of groups with and without atrophy by using quantitative image analysis system. In the group without atrophy, regression analysis of the data on age was made and the 95% confidence interval of the data for age was obtained. No evidence that the tongue becomes atrophic with aging was obtained in the group without atrophy. Patients in the group with atrophy were best separated from those in the group without atrophy statistically when the ratio of tongue area to oral cavity area was regressed on age. Among 11 patients in the group with atrophy, 6 patients were not regarded as having tongue atrophy on clinical neurological examinations. Therefore, the evaluation of midsagittal MRIs is clinically useful.     

Computerized morphometric analysis of human leukemic and lymphomatous cells in various histological environments of central nervous system

The leukemic and lymphomatous cells appear within the central nervous system (CNS) in 5 different environments: in CNS vessels, perivascular spaces, meninges, nervous tissue and in CNS hemorrhages. A computerized analysis of geometric and densitometric parameters of neoplastic cells in these compartments were done for better recognition of penetration and spreading of leukemia and lymphoma within the CNS. A post-mortem neuropathological investigations were carried out on 16 patients deceased due to acute myeloblastic leukemias (M1, M2), blastic phase of chronic myelogenous leukemia, lymphoblastic lymphoma and acute lymphoblastic leukemia. Following nuclear parameters of neoplastic cells were analyzed: area, "form factor", mean, minimal and maximal density. An evident differentiation of nuclear parameters within the CNS environments was found. The nuclei within the perivascular spaces and especially in CNS hemorrhages were significantly shrunken and dense (p < 0.01), but not evidently deformed. The intracerebral infiltrates appeared to be most differentiated group (p < 0.01). Morphometric values of leukemic and lymphomatous cells show regressive changes of neoplastic cells within the CNS perivascular spaces, nervous tissue and in CNS hemorrhages. These changes depend on unfavorable factors in the mentioned CNS environments, and also on time of cell persistence in these regions. Meninges were found to be the only CNS structure facilitating the survival and proliferation of leukemic and lymphomatous cells.     

Prediction of recurrence in meningiomas after surgical treatment

Summary The prognostic significance of nuclear count, nuclear area fraction, and mean nuclear area estimated by automatic image analysis was evaluated in benign meningiomas. One hundred thirty-two meningiomas without recurrences, 39 meningiomas that recurred, and 40 first recurrences were examined. The tumors were classified according to age and eex of patients, localization, and histology; and the correlation between these parameters and the recurrence rate was assessed.The nuclear counts were identical in paraffin sections from meningiomas without recurrences (6.1 nuclei per 1,000 m²) and in meningiomas that recurred (6.4 nuclei per 1,000 m²). The cell count in the recurrences (7.4 nuclei per 1,000 m²) was higher than in the primary tumors. The same relationship was found for the nuclear area fractions, which were identical in primary meningiomas without recurrences and in meningiomas that recurred. The nuclear area fraction was increased in recurrences. The mean nuclear areas were identical in all groups. The histological type was of little significance in prediction of recurrence rate, although bone invasion and necrosis were of some significance. We found a higher recurrence rate in parasagittal meningiomas. Meningiomas that recurred appeared in a younger age group than other meningiomas, and the recurrence rate was higher for males than for females.Supported by grant no. 512-10141 from the Danish Medical Research Council     

Conditional entropy as an indicator of pleomorphism in astrocytic tumors

The entropies of nuclear arrangements as an indicator of pleomorphism are assessed using a morphometric method. Sixty astrocytic tumors (grades I, II, III and IV; 15 cases each) were reviewed and analyzed. All slides were stained with HE and MIB‐1 antibody. The MIB‐1 labeling index (LI) was assessed by counting nuclei under a microscope. Images of HE‐stained slides were digitized and segmented using the watershed algorithm. Then, six nuclear parameters were measured automatically: (i) the number of total nuclei in the image, (ii) percentage of total nuclear area in the image, (iii) the mean area of the nucleus, (iv) the standard deviation of the area of the nucleus, (v) the entropy of nuclear arrangement (Entropy_simple), and (vi) conditional entropy of nuclear arrangement (Entropy_conditional). Entropy_simple was defined according to the area of the nucleus and Entropy_conditional was defined according to both the area of the nucleus and the area of its neighboring nuclei. Image processing and image analysis were performed with public domain software developed in the laboratory. Segmentation of the images resulted in inappropriate segmentation in a few percent of the images. The measurements obtained for each parameter were classified using discriminant analysis. The percentage of correct classification with Entropy_conditional was 62%, which was the highest value among all the measurements. Classification based on the combination of all measurements resulted in a rate of correct classification of 88%. Thus, conditional entropy of nuclear arrangement is useful for grading of astrocytic tumors and it is proposed as an indicator of pleomorphism.     

DAPI-DNA cytofluorometric study of glioma cells--application of DAPI-DNA cytofluorometry to paraffin embedded archival glioma tissue for nuclear DNA content analysis]

Using DAPI-DNA cytofluorometry, the author analyzed nuclear DNA content of formalin fixed, paraffin embedded, glioma material obtained from 14 glioma cases at surgery. Sections of 10 microns were deparaffinized. Following simultaneous DAPI (4,6-diamidino-2-phenylindole dihydroporphyrin chloride)/HP (hematoporphyrin) staining, DAPI binds DNA and DNA-DAPI complexes emit blue fluorescence when exited by ultraviolet (UV) light. Through Zeiss fluorescence microscope, the author measured nuclear fluorescence intensity with histological verification of glioma cells. A DNA histogram was obtained with fluorescence intensity recorded on the abscissa and number of cells plotted on the ordinate. Samples of 20 normal non-neoplastic astrocytes taken from apparently normal brain tissue included in the histological slide were used as diploid (2 C) control. Based on DNA content, tumor cells were classified into 4 groups: N-group composed of cells with 2 C DNA content (normoploid), S-group with less than 2 C (hypoploid), L-group more than 4 C (hypertetraploid), I-group between 2 C and 4 C (intermediate ploidy). Intermediate ploidy was significantly higher and normoploid was significantly lower in glioblastoma compared with those of benign astrocytoma. Thus, DNA content and histological malignancy were well correlated. Due to limitation of measuring diaphragm of turret in the microscope, some extra large cell could not be included in it and was excluded from the measurement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microscopic morphometry of the spinal cord with cervical spondylotic myelopathy

Quantitative studies with morphometric assessments were carried out on the slpinal cord of four cases (aged 71–88 years) with cervical spondylotic myelopathy (CSM), and compared with four normal spinal cords from age-matched cadaver specimens (aged 76–84 years). The histological preparation of the slpinal cord was made after embedding in celloidin and staining with luxol fast blue-periodic acid-Schiff-hematoxylin and Klüver-Barrera methods. the number, average transverse area and perimeter of the anterior horn cells (AHC) in the Rexed's lamina IX at C3, C5, C6 and L1 levels were counted and measured; the number, average transverse area and perimeter of axon in the posterior funiculus at C3 level and in the lateral corticospinal tracts at L1 level were also counted and measured under high magnification with oil immersion (1340 times), using a combination of an electronic optical planimeter, a microscope with a drawing tube, and a personal computer. The results can be summarized as: (i) The numbers of AHC in CSM at C5, C6 and L1 levels were significantly decreased compared with normal controls, and the average transverse area of AHC at C6 and L1 levels showed a decrease in varying degrees (p<0.05 or P<0.01, respectively). However, the number and average area of AHC in CSM at C3 level did not show any difference. (ii) The number and average transverse area of axons in the posterior funiculus with CSM at C3 level showed a significant reduction compared with normal controls (P<0.01 and P<0.05, respectively). (iii) There was an obvious decrease in the number of axons in the lateral corticospinal tracts of CSM at L1 level (P<0.01), but the average area of axons showed no statistical reduction. It can be deduced from these results that there were ascending degeneration of the posterior funciculus and descending degeneration of the lateral corticospinal tracts above and below the segments of comparession caused by CSM. The loss in number and reduction in transverse area of AHC mainly occurred in those segments involved with compression. However, the result of AHC at L1 level revealed that CSM may have a distal influence on AHC below thesegments of compression.     

Significance of the factors in wound healing for the origin of chronic subdural hematoma--fibronectin and its related substances]

The role of substances for wound healing in chronic subdural hematoma was investigated. Fibronectin, blood coagulation factor XIII (F X III), alpha 2 -plasmin inhibitor (alpha 2-PI) and alpha 2-PI plasmin complex (PIC) in hematoma fluid were measured, sixty cases of hematoma fluid (15 cases were bilateral chronic subdural hematomas) were used for analysis. The levels of fibronectin in hematoma fluid ranged widely from 40 to 1068 micrograms/ml. The levels of F XIII (except 1 case) in the hematoma fluid were less than 70% (normal plasma level 72-144%). And also the levels of alpha 2-PI in the hematoma fluid were lower than that in normal blood plasma (85-115%). Fibrin, fibronectin, alpha 2-PI and collagen crosslinks to these proteins by the catalytic action of the activated F XIII. These substrate proteins (except fibronectin) and F XIII were extremely low levels for wound healing. Histological analysis of the membrane with dura mater obtained from 13 patients was performed by Abidin-Biotin peroxidase Complex Method. Fibronectin was identified in outer membrane especially in sinusoidal layer. In normal wound healing, fibronectin appears early with the invading fibroblast and disappeares within 5 weeks from injury. But in chronic subdural hematoma it was not disappeares in 8 weeks after the head injury. The fact indicates the neomembrane of the chronic subdural hematoma is not in healing stage. This condition in chronic subdural hematoma is unfavorable for wound healing. Thus, author suspected that in early phase of wound healing after the head injury fibronectin and its related substances may play a role in the formation of chronic subdural hematoma.     

Effect of anticonvulsants on pentylenetetrazol-induced power spectrum changes in electroencephalograms in rats

The effect of anticonvulsants on pentylenetetrazol (PTZ)-induced EEG power spectrum changes was examined. When the minimum dose of PTZ (15 mg/kg) was administered intravenously twice, with an interval of 80 min, a clear EEG power spectrum change was observed after the second PTZ administration, irrespective of whether or not the first PTZ administration evoked marked EEG changes. We defined the values F/N, S/N and S/F. The value F/N, obtained by dividing the power spectrum area after the first PTZ administration by the normal power spectrum area, was 1.06 +/- 0.05 (mean +/- S.E.). The value S/N, obtained by dividing the power spectrum area after the second PTZ administration by the normal power spectrum area, was 2.00 +/- 0.21. The value S/F, obtained by dividing S/N by F/N, was 1.86 +/- 0.16. The S/F value was almost constant regardless of whether or not the first PTZ administration could evoke marked EEG changes. The effect of anticonvulsants was examined by S/F value changes, and 100 mg/kg of PHT completely inhibited the double PTZ effect. Phenobarbital, ethosuximide and sodium valproate also inhibited the double PTZ effect. Using the S/F value of the EEG power spectrum with minimum dose double PTZ administration, quantitative evaluation is possible for anticonvulsant drugs.     

A quantitative morphometrical study of neuron degeneration in the substantia nigra in Parkinson''s disease

We studied the pigmented neurons of the substantia nigra (SN) from 8 controls and 20 patients with Parkinson's disease (PD) using a computerized morphometric methodology. On the basis of neuronal topography, several anatomic regions were outlined in the SN. In these subrogions the area, perimeter, diameter of the cell bodies and cell numbers were measured and were counted in the controls and PD patients. The measurements were made at the level of the exit of the third cranial nerve from the brain stem. In PD patients, when the whole SN was considered, the mean area, mean perimeter and diameter of the pigmented cell bodies were significantly reduced by 35%, 20% and 21% respectively from the control mean values. Regionally, the pigmented neuron area in the medial ventral part (VM), medial dorsal part (DM), lateral ventral part (VL), lateral dorsal part (DL) and pars lateralis part (PL) showed a significant reduction of 33–41% as compared to controls. In these subregions, a significant decrease in PD patients from the control mean values was seen both in the pigmented neuron perimeter, by 19–26%, and the diameter by 19–25%. This decrease in cell size suggests that, in PD patients, the remaining pigmented neurons in the SN are in a process of degeneration and atrophy. In PD patients the number of pigmented neurons in the whole SN decreased about 76% from control values. Evaluation of the influence of cell size on the apparent quantity of cells in sections indicates, however, that in PD patients the impact of true loss of pigmented neurons is far more dramatic than the impact of their decrease in size.     

Morphometry of astrocyte and oligodendrocyte ultrastructure after portocaval anastomosis in the rat

Summary The ultrastructure of astrocytes and oligodendrocytes was investigated in rats 10 days, 30 days, and 10 weeks after portocaval anastomosis (PCA). Cell and nuclear sizes were measured by planimetry on randomly sampled cells magnified×24,000. The volume fractions of mitochondria, glia fibrils, and lipofuscin granules were measured in astrocytes by electronic image analysis. The mitochondrial profile area distribution and oligodendrocyte mitochondrial content were likewise estimated. All PCA animals had an increased astrocyte cell and cytoplasmic area, and after correction for cytoplasmic edema all groups had an enhanced mitochondrial fraction and mitochondrial number. The mitochondrial sizes were increased in all PCA groups. The mitochondrial profile area distribution curves did not suggest more than one group of mitochondria. All PCA groups had increased fractions of lipofuscin granules and glia fibrils. The oligodendrocytes had a slight fall in cell, nuclear, and cytoplasmic area after 30 days of shunting, and the mitochondrial fraction was diminished. After 10 weeks of PCA, all changes were reversed to normal values. It is concluded that the astrocytes are the active cells in the brain metabolism of ammonium. The oligodendrocytes seem to be dependent on neuronal integrity and do not contribute to the brain ammonium metabolism. The increase in astrocyte lipofuscin granules content may be explained by a beginning neuronal loss.Abbreviation (PCA) Portocaval anastomosis     

Triple stimulation technique (TST) in amyotrophic lateral sclerosis.

OBJECTIVE: The authors studied amyotrophic lateral sclerosis (ALS) patients using triple stimulation technique (TST) to detect upper motor neuron (UMN) involvement. METHODS: Nineteen ALS patients (aged 45-72 years) were enrolled in the study. According to the El Escorial criteria, 6 diagnoses were suspected or possible, 6 probable, and 7 definite. Patients were examined clinically, with conventional (single-pulse) transcranial magnetic stimulation (TMS), and with TST (on one side only). RESULTS: Among the whole group of patients, TST appeared to be more sensitive than conventional TMS techniques. In particular among suspected/possible ALS patients, TST area ratio was pathologic in 100%, while single-pulse TMS was abnormal only in 50% of cases. Overall, the use of TST area ratio was more sensitive than the analysis of TST amplitude ratio. CONCLUSIONS: The results suggest that TST might be more sensitive and useful in the diagnosis of subclinical UMN involvement than conventional TMS techniques, even if TST is performed on one side only.     

A Golgi and morphometric study of the ectopic granule cells in the molecular layer of the rat cerebellum

The morphological types of isolated ectopic granule cells (EGCs) were examined with Golgi-Rio Hortega staining in the cerebellar molecular layer of adult normal rats. The EGCs showed a significant reduction in the number of dendrites (mean 2.42 +/- 0.07) with respect to the controls (mean 3.97 +/- 0.09), and they usually exhibited poorly developed dendritic terminals. The karyometric analysis on semithin sections indicated that the average nuclear area in EGCs was significantly smaller (16.62 +/- 0.20 micron 2) than in normally positioned granule cells (21.08 +/- 0.24 micron 2).     

Distribution of nuclear pores and chromatin organization in neurons and glial cells of the rat cerebellar cortex

Nuclear pores were assessed on freeze-fracture replicas from different neuronal and glial cell types of the rat cerebellar cortex. Nuclear diameter and perimeter were measured on semithin sections, and nuclear surface area and volume were calculated from these data. The proportion of inner nuclear membrane in apposition to condensed chromatin was measured on thin sections. The values of nuclear pore numerical density (number/micron2) were as follows (mean +/- S.D.): Purkinje cells, 22 +/- 3; Golgi cells 17 +/- 3; granule cells, 6 +/- 4; stellate and basket cells, 6 +/- 1; protoplasmic astrocytes, 11 +/- 1; Bergmann glia, 10 +/- 1; oligodendrocytes, 6 +/- 1. The total number of nuclear pores per nucleus varied from 18,451 +/- 2,336 (Purkinje cells) to 621 +/- 394 (granule cells) among neurons, and from 1,782 +/- 162 (protoplasmic astrocytes) to 402 +/- 67 (oligodendrocytes) among glial cells. The number of nuclear pores per unit nuclear volume (number/micron3), a parameter related to nucleocytoplasmic transport capacity, varied from 15 +/- 2 in Purkinje cells to 6 +/- 4 in granule cells. The proportion of nuclear membrane free of condensed chromatin was significantly (P less than 0.01) correlated to pore numerical density and total number of pores per nucleus. Some nuclear pores were associated in clusters of two or more pores. The amount of pore clustering was measured by counting the proportion of pores associated in clusters. This proportion varied among the different cell types from 82% in Purkinje cells to 44% in stellate and basket cells. The amount of pore clustering showed a positive linear correlation to pore numerical density and pore number per nucleus. However, the proportion of pores in clusters was not significantly correlated with the amount of condensed chromatin applied against the inner nuclear membrane.     

Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length

Summary A prospective study was undertaken to select mentally normal old subjects and patients with senile dementia of the Alzheimer type (SDAT). The test score of Blessed et al. (1968) (BTS) was used to determine the severity of mental impairment. A pathologic study confirmed the diagnosis of either SDAT or normal brain aging at postmortem examination in 12 cases. The cortical area and the cortical perimeter of the different cerebral lobes were measured on 1-cm-thick coronal sections using a semiautomatic image analyzer. Cortical length and thickness were calculated using perimeter and area values. BTS was significantly correlated with both the area (r=0.7695,P=0.003) and the length (r=0.7421,P=0.006) of the temporal cortex. There was no significant correlation between BTS and thickness of the temporal cortex (r=0.559,P=0.059). These results show that reduction of length is one of the major determinants of cortical atrophy. Although this has to be confirmed by histological study, they favor the hypothesis of a column-selective atrophy in SDAT which should be considered in the interpretation of the microscopic data.Supported by INSERM (PRC Santé Mentale et Cerveau no. 13 3015) and FRMF     

Comparison of different prothrombin complex concentrates--in vitro and in vivo studies

The potency and tests for thrombogenicity were studied prospectively in 7 different (two lots of each brand, A-G) prothrombin complex concentrates (PCC). Human albumine (H) and a factor IX concentrate (I), served as controls. The potency of coagulation factors and inhibitors varied considerably. Two brands (E, F) contained no protein S, additionally one brand contained no protein C. Two preparations exhibited high amidolytic activities, especially towards the thrombin-sensitive chromogenic substrate S-2238, in vitro. These activities could be quenched in part by the addition of hirudin or antithrombin III. The heparin and antithrombin III content of the PCCs was significantly different, and, after addition of antithrombin III an increase of thrombin-antithrombin III complexes in 2 preparations (B, D) was observed in vitro. Additionally, three brands (B, D, F) caused more severe cardio-pulmonary reactions in rabbits, associated with an increase of fibrin split products for brands B and D. We conclude that the use of these preparations in patients, in whom an acquired protein C or S defect, or a hypercoagulable state, can be suspected, cannot be recommended.