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Objective: To describe structural and biochemical evidence from postmortem brains that implicates the reciprocal connections between the mediodorsal thalamic nucleus and the prefrontal cortex in cognitive symptoms of schizophrenia. Method: The estimation of the regional volumes and cell numbers was obtained using stereological methods. The biochemical analyses of molecular expression in postmortem brain involve quantitative measurement of transcripts and proteins by in-situ (RNA) or Western blot/autoradiography in brains from patients with schizophrenia and comparison subjects. Results: Stereological studies in postmortem brain from patients with schizophrenia have reported divergent and often opposing findings in the total number of neurons and volume of the mediodorsal (MD) thalamic nucleus, and to a lesser degree in its reciprocally associated areas of the prefrontal cortex. Similarly, quantitative molecular postmortem studies have found large inter-subject and between-study variance at both the transcript and protein levels for receptors and their interacting molecules of several neurotransmitter systems in these interconnected anatomical regions. Combined, large variation in stereological and molecular studies indicates a complex and heterogeneous involvement of the MD thalamic-prefrontal loop in schizophrenia. Conclusion: Based on a considerable heterogeneity in patients suffering from schizophrenia, large variation in postmortem studies, including stereological and molecular postmortem studies of the MD thalamus and frontal cortex, might be expected and may in fact partly help to explain the variable endophenotypic traits associated with this severe psychiatric illness. [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]

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]

Abstract: The Göttingen minipig (G-mini) is increasingly used as a non-primate model for human neurological diseases. We applied design-based stereology on five groups of G-minis aged 1 day, 14 days, 30 days, 100 days, and 2 years or older to estimate the pattern of postnatal neuron number development in the neocortex. Two time periods for the postnatal increase of neocortical neuron number were observed from the time of birth to day 14 (P=0.013) and from day 30 to day 100 (P<0.001). No significant change in neuron number was found from day 14to 30 (P=0.58) and day 100 onward (P=0.39). The average estimated total number of neurons in the neocortex was 236, 274, 264, 338, and 353 million, respectively. Since neurogenesis and neuronal migration in the human neocortex are generally accepted to be complete before term, the application of G-mini as human disease models may be inappropriate before day 100. However, G-mini may serve as a valuable model for the studies of ongoing neurogenesis in the living brain. [Copyright &y& Elsevier]

Abstract: White matter changes have been reported as part of Alzheimer dementia. To investigate this, the total subcortical myelinated nerve fiber length was estimated in postmortem brains from eight females (age 79–88 years) with severe Alzheimer''s disease (AD) and compared with brains from 10 female control subjects (age 74–92 years). A stereological method for estimating myelinated brain fibers includes sampling systematically, randomly from the white matter, and counting fibers in unbiased counting frames using light microscopy at approximately 6000× magnification. The diameter of each counted fiber was measured to obtain the diameter distribution of myelinated fibers in both groups. The mean total myelinated fiber length was 81,554 km in the AD group and 78,896 km in the control group (P=0.63). All other measured parameters were also unaffected in the AD brains: The mean fiber length density was 248 km/cm3 in the AD group and 247 km/cm3 in the control group; the volume of white matter was 329 cm3 (AD) and 321 cm3 (control) and the volume density of myelinated fibers to white matter tissue volume was 0.30 in AD group and 0.31 in the control group. This is the first study of subcortical brain white matter fiber length using a stereological method on postmortem brains from AD patients and control subjects. [Copyright &y& Elsevier]

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]

The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69 years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small neurons, oligodendrocytes, and astrocytes) were estimated using the optical fractionator technique. The DS brains had an average of 3.41 × 10 6 total neurons in the MDT nucleus in contrast to 5.97 × 10 6 in the controls, with no overlap (2 p = 0.004), affecting large (projecting) and small (local inhibitory) neurons nearly equally. In contrast, we observed no significant differences in either glial cell population. The cortical structures of the same four DS brains were previously estimated to be half the normal size of controls with a reduction in cell numbers whereas the basal ganglia were unaffected. As DS brains are affected by developmental delay, premature aging, and Alzheimer-like pathology, the finite cause of the reduced number of cells in MDT nucleus cannot be determined; however, these findings provide stereological evidence for a local reduction in neuron numbers in the MDT nucleus, which could affect the cognitive capacity of patients with DS. [ABSTRACT FROM AUTHOR]

The pathogenesis of hidradenitis suppurativa (HS) is not clearly understood. The nomenclature suggests an important role for the apocrine glands but recent evidence implicates the pilosebaceous unit as a more likely candidate to play a central role in the pathogenesis. Our aim was to estimate the volume of the follicular epithelium, the follicular lumen and the sebaceous glands of patients with HS and healthy controls by means of stereology. Four-millimetre punch biopsies were taken from 21 patients with HS and nine healthy controls, fixed in formalin, embedded in paraffin and stained with haematoxylin and eosin prior to volume estimation using the Cavalieri principle. Sebaceous gland tissue could be visualized in only 10 of 15 suitable hair follicle biopsies from patients with HS but was present in all biopsies from healthy controls ( P = 0·05) and the mean sebaceous gland volume per follicle was one-seventh of that of healthy controls ( P = 0·03). There was no significant difference between patients with HS and healthy controls with regard to follicular epithelium and follicle lumen volume. Our results suggest that the absence or reduced volume of the sebaceous gland may play a role in the pathogenesis of HS. The presence of fibrosis suggests that sebaceous glands are obliterated early in the pathogenesis of HS. [ABSTRACT FROM AUTHOR]

The 3D spatial arrangement of particles or cells, for example glial cells, with respect to other particles or cells, for example neurons, can be characterized by the radial number density function, which expresses the number density of so-called 'secondary' particles as a function of their distance to a 'primary' particle. The present paper introduces a new stereological method, the saucor, for estimating the radial number density using thick isotropic uniform random or vertical uniform random sections. In the first estimation step, primary particles are registered in a disector. Subsequently, smaller counting windows are drawn with random orientation around every primary particle, and the positions of all secondary particles within the windows are recorded. The shape of the counting windows is designed such that a large portion of the volume close to the primary particle is examined and a smaller portion of the volume as the distance to the primary object increases. The experimenter can determine the relation between these volumina as a function of the distance by adjusting the parameters of the window graph, and thus reach a good balance between workload and obtained information. Estimation formulae based on the Horvitz-Thompson theorem are derived for both isotropic uniform random and vertical uniform random designs. The method is illustrated with an example where the radial number density of neurons and glial cells around neurons in the human neocortex is estimated using thick vertical sections for light microscopy. The results indicate that the glial cells are clustered around the neurons and the neurons have a tendency towards repulsion from each other. [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]

Abstract: Anatomical evidence of brain damage from electroconvulsive therapy (ECT) is lacking; but there are no modern stereological studies in primates documenting its safety. Magnetic seizure therapy (MST) is under development as a less invasive form of convulsive therapy, and there is only one prior report on its anatomical effects. We discerned no histological lesions in the brains of higher mammals subjected to electroconvulsive shock (ECS) or MST, under conditions that model closely those used in humans. We sought to extend these findings by determining whether these interventions affected the number of neurons or glia in the frontal cortex or hippocampus. Twenty-four animals received 6 weeks of ECS, MST, or anesthesia alone, 4 days per week. After perfusion fixation, numbers of neurons and glia in frontal cortex and hippocampus were determined by unbiased stereological methods. We found no effect of either intervention on volumes or total number or numerical density of neurons or glia in hippocampus, frontal cortex, or subregions of these structures. Induction of seizures in a rigorous model of human ECT and MST therapy does not cause a change in the number of neurons or glia in potentially vulnerable regions of brain. This study, while limited to young, healthy, adult subjects, provides further evidence that ECT and MST, when appropriately applied, do not cause structural damage to the brain. [Copyright &y& Elsevier]

Abstract: Stereological cell counting was applied to post-mortem neocortices of human brains from 31 normal individuals, age 18–93 years, 18 females (average age 65 years, range 18–93) and 13 males (average age 57 years, range 19–87). The cells were differentiated in astrocytes, oligodendrocytes, microglia and neurons and counting were done in each of the four lobes. The study showed that the different subpopulations of glial cells behave differently as a function of age; the number of oligodendrocytes showed a significant 27% decrease over adult life and a strong correlation to the total number of neurons while the total astrocyte number is constant through life; finally males have a 28% higher number of neocortical glial cells and a 19% higher neocortical neuron number than females. The overall total number of neocortical neurons and glial cells was 49.3 billion in females and 65.2 billion in males, a difference of 24% with a high biological variance. These numbers can serve as reference values in quantitative studies of the human neocortex. [Copyright &y& Elsevier]

Abstract: Since the turn of the last century, the average life expectancy has risen considerably. Lengthening of life span has little merit if the quality of life is not preserved and in the elderly the decline in memory and cognitive abilities is of great concern. We applied a stereological technique, the planar rotator method, in an optical vertical design to get an estimation of the three-dimensional volume of the neocortical nuclei and perikaryon volume in neurons from brain neocortex and the four cortical lobes in 39 normal human subjects ranging from 18 to 93 years old. Although there was a trend with p values of 0.07, the mean global neocortical perikaryon volume was not significantly larger in men compared with women and the mean neuronal nuclear volume was not significantly different in the two sexes. Nonetheless, we found gender differences in both frontal and temporal cortices in the perikaryon volume, but not in the nucleus volume. Earlier findings of a higher neocortical neuron number in men compared with women was repeated in this study and, not unexpectedly, the sum of all neuronal perikaryon volume in neocortex was significantly higher in men than women, primarily as a result of a higher neocortical neuron number. [Copyright &y& Elsevier]

Abstract: A new stereological probe, the saucer, was used for estimating three-dimensional (3D) spatial distributions of particles around particles. The advantages of the saucer include that the measurements and the results are in 3D and the size and design of the probe enables the investigator to sample a proportion of a suitable size to have a reasonable relationship between workload and the information obtained. In this paper the method is used on vertical sections to investigate the spatial distribution of astrocytes, oligodendrocytes, microglial cells, endothelial cells and secondary neurons around primary neurons in the human neocortex (divided into frontal-, temporal-, parietal- and occipital cortex) of young and old subjects free of neurological or psychological disease to test if age and gender has any influence on the cell distribution in human neocortex. Plots of the spatial distribution of the densities of all cell types did not show any difference between women and men and no difference between brains of young and old subjects. Thus it is concluded that in this small study the spatial distribution of the densities of the different types of cells in brains from individuals free of neurological disorders was independent of age and gender. [Copyright &y& Elsevier]

Abstract: By means of i.c.v. administration of preaggregated oligomeric β-amyloid (Aβ)25-35 peptide it was possible in rats to generate neuropathological signs related to those of early stages of Alzheimer’s disease (AD). Aβ25-35-administration induced the deposition of endogenously produced amyloid protein. Furthermore, quantitative immunohistochemistry demonstrated time-related statistically significant increases in amyloid immunoreactivity, tau phosphorylation, microglial activation, and astrocytosis, and stereological investigations demonstrated statistically significant increased neuronal cell death and brain atrophy in response to Aβ25-35. Finally, the Aβ25-35-administration led to a reduced short-term memory as determined by the social recognition test. A synthetic peptide termed FGL derived from the neural cell adhesion molecule (NCAM) was able to prevent or, if already manifest, strongly reduce all investigated signs of Aβ25-35-induced neuropathology and cognitive impairment. The FGL peptide was recently demonstrated to be able to cross the blood–brain-barrier. Accordingly, we found that the beneficial effects of FGL were achieved not only by intracisternal, but also by intranasal and s.c. administration of the peptide. Furthermore, FGL-treatment was shown to inhibit the activity of GSK3β, a kinase implicated in signaling regulating cell survival, tau phosphorylation and the processing of the amyloid precursor protein (APP). Thus, the peptide induced a statistically significant increase in the fraction of GSK3β phosphorylated on the Ser9-position, a posttranslational modification known to inhibit the activity of the kinase. Hence, the mode of action of FGL with respect to the preventive and curative effects on Aβ25-35-induced neuropathological manifestations and cognitive impairment involves the modulation of intracellular signal-transduction mediated through GSK3β. [Copyright &y& Elsevier]

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]

Abstract: The total cell numbers were estimated in the neocortical part of the human telencephalon in 10 normal brains of newborn babies within four major developmental zones: the cortical plate/marginal zone, the subplate, the intermediate zone and the ventricular/subventricular zone. Furthermore, the total number of neuron and glial cells was estimated in the cortical plate. The gestational ages ranged from 38+0–42+5 weeks+days of gestation. The mean total cell number was 32.6×109 (coefficient of error=0.04) and the total number of neurons in the cortical plate 19.8×109 (coefficient of error=0.06). This indicates that the total number of neocortical neurons equals the total number in the adults, which, however, is not the case for the glial cells. [Copyright &y& Elsevier]

A screening procedure was developed to provide quantitative estimates of structural parameters, regional volumes and neuron number, in a neurotoxicologic study of the Göttingen minipig brain. The study material consisted of normal controls and brains collected from young minipigs which had been exposed in utero to the mitotic inhibitor methylazoxymethanol acetate (MAM). Based on stereological principles and systematic sampling techniques, volumetric data from pre-selected regions of the pig brain was obtained using Cavalieri’s principles and point-counting. Secondarily, estimates of total hemispheric neocortical cell numbers were obtained from pre-selected groups to test the potential effect of MAM on neuron number. No significant differences were observed in volume of the pre-selected regions of MAM intoxicated pigs nor in estimates of total neocortical neuron number. [ABSTRACT FROM AUTHOR]

Broholm H, Andersen B, Wanscher B, Frederiksen JL, Rubin I, Pakkenberg B, Larsson HBW, Lauritzen M. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis. Acta Neurol Scand 2004: DOI: 10.1111/j.1600-0404.2004.00207.x © Blackwell Munksgaard 2004. We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant iNOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age and sex showed no such changes. Our data support the hypothesis that NO is a pathogenic factor in MS, and that NOS IR is strongly expressed in brain regions appearing normal by MRI. [ABSTRACT FROM AUTHOR]

Korbo L, Amrein I, Lipp H-P, Wolfer D, Regeur L, Oster S, Pakkenberg B. No evidence for loss of hippocampal neurons in non-Alzheimer dementia patients. Acta Neurol Scand 2003 DOI: 10.1046/j.1600-0404.2003.00182.x © Blackwell Munksgaard 2003. To use stereological methods for estimating the total number of neurons in hippocampi of non-Alzheimer demented patients. Hippocampi from six women with severely impaired memory but without Alzheimer pathology were compared with six mentally intact age-matched female controls. The total number of neurons was estimated in the granule cell layer of the dentate gyrus, the hilus of the dentate gyrus, the pyramidal cell layer of CA3 and CA2, the pyramidal cell layer of CA1 and the cellular layer of subiculum using the optical fractionator. The total neuron number was the same in the dementia cases, 22.4 × 106, compared with 22.7 × 106 in the controls ( P = 0.85). No region-specific group differences or side difference were found. Two cases without clinical signs of dementia but with abundant plaques and tangles in hippocampus and neocortex had total neuron numbers within normal limits. Our results indicate that severely impaired memory can occur in the presence of intact numbers of hippocampal neurons in non-Alzheimer dementia and that nerve cell loss in the hippocampus might be characteristic for Alzheimer's disease, and perhaps other forms of primary cortical dementia. [ABSTRACT FROM AUTHOR]

In a stereological study of the human substantia nigra (SN), the total number of melanin-positive and melanin-negative neurones from 28 male subjects aged 19–92 years was estimated using a uniform sampling design and optical disectors. There was a significant decrease in the total number of melanin-positive neurones as a function of age (r 2 =0.18, residual-CV=0.35, 2P =0.032). Using the rotator method, the size distribution of the melanin-positive neurones was estimated and showed a significant difference in mean cell volume of melanin-positive neurones between the seven youngest (21 077 µm3 ) and the seven oldest individuals (32 011 µm3 ), 2P =0.022. Using a combination of the total number of melanin-positive neurones and their size distribution, the total perikaryon volume of melanin-positive neurones could be estimated and showed no decrease with increasing age (r 2 =0.01, residual-CV=0.41, 2P =0.62). Age-related decline in dopamine-transporter neurones within the SN might explain the occurrence of extrapyramidal symptoms in many elderly individuals. Although age-related cell hypertrophy is usually considered to be an indication of cell degeneration or necrosis, this might not always be the case. The fact that motor symptoms, although present in many of the elderly, are of a limited nature despite the high percentage of lost neurones could be due to a compensatory increase in the cell body of dopamine-producing SN neurones. Thus, the total amount of cell substance capable of producing the essential transmitters might not be reduced to a critically low level as a result of ageing. [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]

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]

A quantitative, stereological method to assess the volume of Schistosoma mansoni granulomas is presented and its use demonstrated in a study of zinc-deficient animals. Twenty-six mice were divided into two groups, and given zinc-deficient or control food. After 4 weeks, the mean weight gain and thymus size were lower in the mice on the zinc-deficient diet. Eight mice in each group were then each infected with 60 S. mansoni cercariae and these mice were killed 12 weeks post-infection. There were then more eggs in the livers of the zinc-deficient mice than in those of the infected controls (7400/female worm v. 3300/female worm; P = 0.02), probably because of impaired intestinal egg expulsion and impaired resorption of eggs in the deficient mice. The median proportion of each liver occupied by granulomas was 0.11 among the zinc-deficient mice and 0.09 among the pair-fed, control mice (P = 0.08), and the median liver volumes were 1400 and 1450 mul (P = 0.49), respectively. The computed median volume of all the granulomas in each liver was 160 mul in zinc-deficient and 132 mul in control mice (P = 0.32), while median granuloma volume per egg was 8.6 and 8.7 nl (P = 0.93), respectively. In contrast to conventional methods, modern stereological methods can provide estimates of granuloma volume or granuloma volume fractions without any assumptions about the size, shape, orientation or distribution of the granulomas in the liver. [ABSTRACT FROM AUTHOR]