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Aims: Indices of brain volume [grey matter, white matter (WM), lesions] are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology and demyelination. Methods: Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa, the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (× 60) following stereological principles. Grey and WM demyelination was outlined on myelin basic protein immunostained sections, and expressed as percentages of cortex and WM respectively. Results: In MS, the mean number of neurons was 14.9 ± 1.9 billion vs. 24.4 ± 2.4 billion in controls (P < 0.011), a 39% difference. The density of neurons was smaller by 28% (P < 0.001) and cortical volume by 26% (P = 0.1). Strong association was detected between number of neurons and cortical volume (P < 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the WM, however, neither correlated with neuronal loss. Only weak association was detected between number of neurons and WM volume. Conclusion: Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS. [ABSTRACT FROM AUTHOR]

Background and Objectives Autologous platelet-rich fibrin ( PRF®) is prepared by the automatic Vivostat® system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase ( MMP)-9 were quantified using novel analytical methods. Materials and Methods Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. Results The number of leucocytes and erythrocytes was reduced ( P < 0·001), whereas platelets increased ( P < 0·001) in fibrin-I versus whole blood. PRF contained 982 ± 206 × 109 platelets/l representing 3·9-fold ( P < 0·001) enrichment relative to whole blood. Growth factor abundance in Vivostat PRF and serum was in descending order: transforming growth factor-β1 [5·1-fold higher in PRF than serum, P < 0·001] > platelet-derived growth factor ( PDGF)- AB [2·5-fold, P < 0·01] > PDGF- BB [1·6-fold, P < 0·05] > vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P < 0·001]. MMP-9 was reduced 139-fold ( P < 0·001) compared with serum, reflecting leucocyte depletion in PRF. Conclusion The gained knowledge on platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. [ABSTRACT FROM AUTHOR]

Quantitative morphological studies of the healthy epidermis are essential in providing a range of parameter estimates that can be considered within the range of normality. Stereology is a set of statistical tools that provides potentially unbiased and precise estimates of 3-dimensional tissue characteristics from 2-dimensional sections. We set out to establish reference values for the volume of the viable epidermis contained within a four-millimetre punch biopsy (Vepi), the volume of the stratum corneum (VSC) and the surface area of the dermo-epidermal junction(ADEJ) in 4 predetermined body regions by use of stereology. Four-millimetre punch biopsies were taken from 20 freshly diseased corpses, fixed in formalin and embedded in paraffin. Vepi, VSC and ADEJ were established stereologically for all 4 body locations followed by pairwise comparison of means after Bonferroni correction. Vepi was significantly larger in the sole compared to all other body locations (p < 0.01). Furthermore, linear regression analysis showed a strong linear relationship between Vepi and VSC in the sole (r = 0.70). Our results suggest that the viable layers of the epidermis might also serve a mechanical function, either directly or by providing the stratum corneum with keratinocytes to support the hyperkeratosis in the weight-bearing parts of the skin. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Severe brain damage is often followed by serious complications. Quantitative measurements, such as regional volume and surface area under various conditions, are essential for understanding functional changes in the brain and assessing prognosis. The affected brain tissue is variable, hence traditional imaging methods are not always applicable and automatic methods may not be able to match the individual observer. Stereological techniques are alternative tools in the quantitative description of biological structures, and have been increasingly applied to the human brain. In the present study, we applied stereological techniques to representative CT and MRI brain scans from five patients to describe how stereological methods, when applied to scans of trauma patients, can provide a useful supplement to the estimation of structural brain changes in head injuries. The reliability of the estimates was tested by obtaining repeated intra- and interobserver estimates of selected subdivisions of the brain in patients with acute head injury, as well as in an MR phantom. The estimates of different subdivisions showed a coefficient of variation (CV) below 12% in the patients and below 7% for phantom estimation. The validity of phantom estimates was tested by the average deviation from the true geometric values, and was below 10%. The stereological methods were compared with more traditional region-based methods performed on medical imaging, which showed a CV below 7% and bias below 14%. It is concluded that the stereological estimates may be useful tools in head injury quantification. [ABSTRACT FROM AUTHOR]

Hippocampal atrophy and neuron loss are early and reproducible findings in Alzheimer's disease, and recent magnetic resonance imaging studies indicate that hippocampal atrophy may also be present in Parkinson's disease (PD). To determine whether or not cell loss occurs in PD, we estimated the total neuron and glial cell numbers as well as the total volume unilaterally in the hippocampi of eight demented PD patients and eight control subjects. Cell numbers were estimated in the neuron-containing layers of CA1, CA2-(3), CA4, the dentate gyrus, and subiculum using the optical-fractionator technique. The Cavalieri method was used to estimate the volume of the total hippocampus and its subregions. We did not find significant differences in cell numbers or volumes in PD brains when compared with control subjects. Our results thus indicate that hippocampal atrophy and cell loss are not necessarily involved in the memory impairment and dementia observed in PD. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Although the maximum human lifespan has not increased in recent history, average life expectancy has risen dramatically since the beginning of the last century. Lengthening of lifespan has little merit if the quality of life is not preserved. In the elderly, the decline in memory and cognitive abilities is of great concern, as is motor weakening, which increases with age. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. Therefore, the aging of this system has both clinical and vocational aspects. This review includes studies quantitating age-related changes of the nigrostriatal system, with emphasis on the use of stereological methods, and provides tables of stereological studies performed in the nigrostriatal system. [ABSTRACT FROM AUTHOR]

To understand the dynamics of islet population, especially during conditions with growth of the total islet mass, it is important to have reliable estimators of parameters describing the quantitative appearance of the islet population. We describe a stereological estimator of the volume-weighted mean islet volume based on unbiased assumption-free stereological principles. The volume-weighted mean islet volume is the mean islet volume if the islets are weighted (sampled) proportional to their volume. This method allows simultaneously unbiased estimation of the total islet mass. With use of this method, 22 male Sprague-Dawley rats within the age span of 34-102 days old were investigated. We found a linear correlation (P < 0.001) between total islet mass and the volume-weighted mean islet volume. The results support models demonstrating that the physiological growth of the total islet mass in the period studied is totally or mainly caused by proportional growth of existing islets. The functional meaning of the volume-weighted mean islet volume is discussed, and previous methods to study the mean islet volume and islet number are critically evaluated. We propose the volume-weighted mean islet volume to be a biologically useful parameter when describing the mean volume of the pancreatic islets and investigating the differences between experimental groups. [ABSTRACT FROM AUTHOR]

Volume measurements were carried out on 29 brains from institutionalised, chronic schizophrenic patients and 30 age and sex-matched controls using a stereological method. The volumes of the total fixated brain, the hemispheres, the cortex, and the central grey matter of the schizophrenic brains were significantly reduced while the volumes of the ventricles were significantly enlarged compared with the control group. The patients had been diagnosed by a psychiatrist on the basis of their case records as having either a Type I or Type II syndrome according to the symptoms they presented in the first years of their disease. The Type II patients were found to have significantly enlarged ventricles compared with the Type I patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to estimate the volume of the ventricular system comprising lateral plus third ventricles in patients with Gilles de la Tourette's syndrome on computed tomographic (CT) scannings using unbiased stereological principles and to compare that volume with a control group. We found a significantly reduced ventricular volume in 24 patients with Gilles de la Tourette's syndrome (GTS) compared with 28 controls. [ABSTRACT FROM AUTHOR]

Using an unbiased stereological technique, the total numbers of pigmented and non-pigmented neurons were estimated in the substantia nigra of seven patients with Parkinson's disease and seven control patients. Compared with the controls, in which the average total number of pigmented neurons was 550,000, the number of neurons was reduced by 66% in the patients. The average total number of non-pigmented neurons was 260,000 in controls and reduced by 24% in the patients. A significant correlation (r = 0.81) existed between the total numbers of pigmented and non-pigmented neurons in the controls, whereas a similar correlation (r = 0.72) in the patients fell just short of statistical significance. The stereological estimates made in this study are unbiased, in that they are independent of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. The stereological method is considerably more efficient than previous conventional methods. [ABSTRACT FROM AUTHOR]

Volume measurements were carried out on 19 brains from leucotomised schizophrenic patients and 20 age- and sex-matched controls using a stereological method. The volume of the total fixed brain, hemispheres, cortex, white matter, and central grey matter were all significantly reduced compared with controls. White matter and central grey structures were significantly reduced compared with a group of non-leucotomised schizophrenic brains. No difference was found in the size of the lesions in patients who improved compared with the patients who remained unchanged and the outcome was unrelated to lesional asymmetry. Morphometric measurements were correlated to a number of clinical parameters. [ABSTRACT FROM AUTHOR]

During the last seven years 65 patients with Gilles de la Tourette's syndrome have been treated. Pimozide was used as the preferred drug because of our experience of treating other hyperkinesias which indicated fewer side-effects than with haloperidol. Of the 65 patients with Gilles de la Tourette's syndrome, 59 were treated with pimozide alone or in combination with tetrabenazine or clonidine. The dose ranges of pimozide were 0.5-9 mg per day. Eighty-one percent experienced a good clinical response without side-effects. The side-effects seen in our patients were sedation, gain in weight, depression, pseudoparkinsonism and akathisia; acute dystonic reactions, blurred vision, slurred speech and xerostomia did not occur. No cases of tardive dyskinesia were seen. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of the study was to test the hypothesis that the total number of cells in the cortical part of the cerebral wall is the same in intrauterine growth-restricted (IUGR) fetuses, compared with normally grown fetuses. STUDY DESIGN: The total cell number in the cerebral wall was estimated in 9 severely affected IUGR fetuses and 15 controls using the optical fractionator. Cell numbers were estimated within 4 developmental zones. The gestational ages were 19-41 weeks. RESULTS: The total cell number in the future cortex was significantly reduced in the IUGR fetuses, compared with controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth and a significant decrease in cell number in the future cortex. [ABSTRACT FROM AUTHOR]