Biomedical subjects

J J Kril

Publications and source records attributed to J J Kril.

At least 37 records · Page 2Linked to original sources

PubMed1997

Language-associated cortical regions are proportionally larger in the female brain.

BACKGROUND: Many studies have demonstrated significant sexual dimorphism in verbal ability. However, few studies have examined anatomical differences between the sexes that may underlie such dimorphism. OBJECTIVE: To examine sex differences in the absolute and proportional volumes of the main language-associated regions of the cerebral cortex. DESIGN AND MAIN OUTCOME MEASURES: Control neuropathological case series of consecutive autopsies from a teaching hospital. No significant age-related volume changes were identified in the sample. Two language-associated cortical regions, the superior temporal gyrus (part of the Wernicke area) and its subdivisions (planum temporale, Heschl gyrus, and anterior superior temporal gyrus) and the inferior frontal gyrus (Broca area in the dominant hemisphere), and a non-language-associated region, the frontal pole, were measured using stereological techniques in brains fixed with formaldehyde solution serially sectioned at 3-mm intervals. Volume comparisons between the sexes and between brain hemispheres were performed using 2-way analysis of variance. SETTING: Studies were conducted at the University of Sydney and the Prince of Wales Medical Research Institute, Sydney, Australia. PATIENTS: Ten males and 11 females free from neurologic or neuropathological abnormalities. RESULTS: The volume of the superior temporal cortex, expressed as a proportion of total cerebral volume, was significantly larger in females compared with males (17.8% increase; P = .04). This was accounted for by 1 section of the superior temporal cortex, the planum temporale, which was 29.8% larger in females (P = .04). In addition, the cortical volume fraction of the Broca area in females was 20.4% larger than in males (P = .05). In contrast, no significant differences were found in the proportional volume of the frontal pole or in regional volumes between the left and right hemispheres in either sex group. CONCLUSIONS: Our results suggest that females have proportionally larger Wernicke and Broca language-associated regions compared with males. These anatomical differences may correlate with superior language skills previously demonstrated in females.

Aged↗

PubMed1997

Chronic alcohol consumption does not cause hippocampal neuron loss in humans.

High alcohol consumption for long periods of time causes significant hippocampal neurodegeneration in rodents. A single study using neuronal density measures has reported similar findings in humans. The present study aims to substantiate these findings in human alcoholics using unbiased stereological techniques. Both amnesic (n = 5) and nonamnesic (n = 7) chronic alcoholics were selected and compared with nonalcoholic controls (n = 8) and patients with marked memory loss and hippocampal neurodegeneration caused by Alzheimer's disease (n = 4). Hippocampal volume was significantly reduced in the alcoholics and in patients with Alzheimer's disease. However, in alcoholics the volume reduction occurred exclusively in the white matter, whereas both the gray and white matter were reduced in the patients with Alzheimer's disease. Neuron loss occurred exclusively from the CA1 and subiculum subregions of the hippocampus in Alzheimer's disease. No neuron loss occurred from any subregion of the hippocampus in alcoholics. There were no correlations with age and any of the volume or neuron number measures. Hippocampal volume correlated with brain volume and with the regional gray and white matter volumes within the hippocampus. In addition, hippocampal gray matter volume correlated with the number of CA1 pyramidal neurons. These results do not support the theory that chronic alcohol consumption is neurotoxic to hippocampal pyramidal neurons in humans. Further, the present results suggest that changes observed in rodent models of alcoholism do not parallel those observed in humans, questioning the validity of such models.

Aged↗

PubMed1997

Diencephalic and cerebellar pathology in alcoholic and nonalcoholic patients with end-stage liver disease.

Formalin-fixed sections from the brains of 36 patients (30 alcoholic and 6 nonalcoholic) with autopsy-proven cirrhosis who died while in a hepatic coma were stained with hematoxylin and eosin, and examined for the presence of diencephalic, cerebellar, pontine, and basal ganglia lesions. Significant neuropathology was identified in 23 of 36 cases consisting of mammillary body and thalamic lesions characteristic of Wernicke encephalopathy (WE) (9 cases, all alcoholic patients) and cerebellar degeneration (20 cases, 17 alcoholic and 3 nonalcoholic patients). Clinical diagnosis of WE had been entertained during life in only 2 of these patients. All cases, alcoholic and nonalcoholic, manifested mild to severe Alzheimer's type II astrocytosis. No cases of central pontine myelinolysis nor acquired (non-Wilsonian) hepatocerebral degeneration were found. These findings show that the brains of a high proportion of cirrhotic patients with end-stage liver disease manifest concomitant unsuspected diencephalic and cerebellar pathology. The high incidence of WE underscores the need for early sustained treatment of alcoholic cirrhotic patients with vitamin B1. Evaluation of the neurological sequelae of liver transplantation, particularly of alcoholic patients with end-stage liver disease, may require a careful neurological and radiological assessment both before and after surgery.

Adult↗

PubMed1997

Distinctive pattern of Bergmann glial pathology in human hepatic encephalopathy.

Alzheimer type II astrocytosis is the pathological hallmark of hepatic encephalopathy. These astrocytes undergo a characteristic morphological change and, in addition, lose immunoreactivity for glial fibrillary acidic protein (GFAP). However, a previous study in the portacaval shunted rat, a model of hepatic encephalopathy, revealed increased rather than decreased GFAP immunoreactivity in Bergmann glia, a specialized group of cerebellar astrocytes. In the present study, sections of cerebellar vermis from 15 cirrhotic patients with hepatic encephalopathy and varying degrees of Alzheimer type II astrocytosis were stained using antisera to GFAP. The Bergmann glial cells did not show altered GFAP immunoreactivity compared to controls. In addition, the degree of GFAP immunoreactivity was not correlated with the degree of Alzheimer type II change nor related to the aetiology of the liver disease. These results suggest a differential response of Bergmann glia in human hepatic encephalopathy.

Adult↗

PubMed1997

The cerebral cortex is damaged in chronic alcoholics.

There is some controversy in the literature concerning whether chronic alcohol consumption damages the cerebral cortex. While decreased neuronal density in specific cortical regions is well described in chronic alcoholics, a recent study by Badsberg Jensen and Pakkenberg using unbiased stereological methods questions whether neurodegeneration occurs. In order to assess selective neurodegeneration in the cerebral cortex of chronic alcoholics, regional volumes and unbiased estimates of regional neuronal number (including neuronal identification with calcium-binding proteins) were calculated for 14 chronic alcoholics and 21 controls. Cases were carefully screened to exclude any interfering pathologies. Lifetime and maximum daily alcohol consumption was determined, and homogeneous groups were identified (four chronic alcoholics with Wernicke's encephalopathy and Korsakoff's psychosis, four chronic alcoholics with Wernicke's encephalopathy alone, six chronic alcoholics without Wernicke's encephalopathy or Korsakoff's psychosis, and 21 controls). Brain volume analysis revealed that discrete regions were significantly smaller in the chronic alcoholics compared to controls. As previously shown, white matter regions (particularly in the frontal lobe) were the most significantly reduced in volume. Alcoholics with Wernicke's encephalopathy (either alone or in combination with Korsakoff's psychosis) had significantly smaller white matter volumes than controls or alcoholics without these complications. Medial temporal lobe regions and the thalamus were also reduced in volume. Regression analyses revealed that the volume of both the white matter and thalamus negatively correlated with alcohol consumption. Consistent with the interpretation of previous neuronal density studies, selective neuronal loss was found in the superior frontal association cortex of chronic alcoholics, while no loss occurred from the motor cortex. The number of parvalbumin-, calbindin- and calretinin-immunoreactive neurons was found to be unaltered in chronic alcoholics, suggesting that the neurodegeneration is confined to the non-GABAergic pyramidal neurons. As neurodegeneration was observed in all alcoholic groups, damage to the frontal association cortex is not restricted to alcoholics with the amnesia of Korsakoff's psychosis. These results are consistent with the notion that chronic alcohol consumption is associated with selective neuronal vulnerability. The selective frontal neurodegeneration and the frontal focus of white matter atrophy are supported by neuropsychological, regional blood flow, and magnetic resonance imaging studies of frontal lobe dysfunction in chronic alcoholics and may correlate with abnormalities in working memory.

Adult↗

PubMed1997

Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy.

OBJECTIVES: To establish better operational criteria for the diagnosis of Wernicke's encephalopathy. Current criteria for diagnosing Wernicke's encephalopathy require the presence of three clinical signs (oculomotor abnormalities, cerebellar dysfunction, and an altered mental state), although it has often been reported that most patients do not fulfil all these criteria. METHODS: The clinical histories of 28 alcoholics with neurological and neuropsychological assessments and definitive neuropathological diagnoses were examined to determine clinical signs for use in a screening schedule. Operational criteria were then proposed for differentiating patients with Wernicke's encephalopathy alone or in combination with Korsakoff's psychosis or hepatic encephalopathy. The new criteria for Wernicke's encephalopathy require two of the following four signs; (1) dietary deficiencies, (2) oculomotor abnormalities, (3) cerebellar dysfunction, and (4) either an altered mental state or mild memory impairment. Reproducibility and validity testing of these criteria were performed on 106 alcoholics screened from a large necropsy sample. RESULTS: Despite rater variability with regard to specific symptoms, within and between rater reliability for diagnostic classification using the criteria retrospectively on patient records was 100% for three independent raters. Validity testing showed that Wernicke's encephalopathy was underrecognized only when occurring with hepatic encephalopathy (50% sensitivity). CONCLUSIONS: By contrast with current criteria, the proposed operational criteria show that the antemortem identification of Wernicke's encephalopathy can be achieved with a high degree of specificity.

Alcoholism↗

PubMed1997

The nucleus basalis (Ch4) in the alcoholic Wernicke-Korsakoff syndrome: reduced cell number in both amnesic and non-amnesic patients.

BACKGROUND: The cholinergic nucleus basalis (Ch4) is an exclusive site of neurofibrillary degeneration in alcoholic patients with Wernicke's encephalopathy. AIM: To test the hypothesis that the loss of Ch4 neurons contributes to the memory disorder, Korsakoff's psychosis, commonly seen in Wernicke's encephalopathy. METHODS: Magnocellular basal forebrain neurons were quantified in alcoholic patients with Wernicke's encephalopathy, both with and without Korsakoff's psychosis, and neurologically asymptomatic alcoholic and non-alcoholic controls. Because amnesic and non-amnesic patients with Wernicke's encephalopathy share common periventricular lesions, both thiamine deficient groups as well as alcoholic patients with no neurological complications were included to determine the lesion specific to memory impairment. RESULTS: Ch4 cell number did not differ significantly between alcoholic and non-alcoholic controls and there was no correlation between cell number and lifetime alcohol intake. However, Ch4 cell number in all groups was significantly correlated with the volume of its major projection target, the cerebral cortex. Ch4 cell number in the non-amnesic Wernicke's encephalopathy group was significantly below controls (24%), with cell number in patients with Korsakoff's psychosis 21% below controls. There was considerable overlap in cell number between groups. On discriminant analysis, there was significantly greater cell loss in three non-amnesic patients with Wernicke's encephalopathy than in some patients with Korsakoff's psychosis. The nonamnesic patient with the greatest cell loss was impaired on attentional tasks. CONCLUSION: Whereas neurons in the nucleus basalis are at risk in thiamine deficient alcoholic patients, cell loss is minor and does not account for the profound memory disorder.

Adult↗

PubMed1996

Glial fibrillary acidic protein (GFAP) immunohistochemistry in human cortex: a quantitative study using different antisera.

Glial fibrillary acidic protein (GFAP) is the principal marker for brain astrocytes. The present study aims to examine the variability in GFAP immunohistochemistry in formalin-fixed human brain. Four commercially-available antisera were tested using standardised protocols in the cerebral cortex of three cases with prominent glial reactions and one control. GFAP immunoreactivity was largely confined to the pial surface and white matter in control cortex, with the number of astrocytic cell bodies and processes as well as intensity of staining markedly increased in damaged cortices. A dramatic difference in the pattern of GFAP staining using different antisera was observed and may account for discrepancies between past studies. This variance has important practical implications for the interpretation of results using GFAP immunohistochemistry in human tissue.

Alzheimer Disease↗

PubMed1996

Receptor binding sites and uptake activities mediating GABA neurotransmission in chronic alcoholics with Wernicke encephalopathy.

Superior frontal cortex (SFC) and primary motor cortex tissue was obtained at autopsy from thirteen severe chronic alcoholics with neuropathologically confirmed Wernicke Encephalopathy (WE) and 22 controls. Cases with both WE and cirrhosis showed markedly fewer neurones in SFC than did WE cases without cirrhosis. The extent of the apparent neuronal loss corresponded to an increase in post-synaptic GABAA receptor sites, as assessed by the binding of [3H]muscimol to synaptic membranes. Increased [3H]muscimol binding was not accompanied by an increase in 'central-type' benzodiazepine binding sites: as assessed by [3H]flunitrazepam binding, these sites were apparently unaltered, while as assessed by [3H]diazepam binding, they were decreased. The affinities of the two benzodiazepine ligands varied differently with disease. These discrepancies between [3H]flunitrazepam and [3H]diazepam binding could not be accounted for, either by the presence of a second, diazepam-preferring, 'central-type' benzodiazepine binding site, or by loss of 'peripheral-type' sites. The changes in the post-synaptic GABAA-benzodiazepine receptor sites did not reflect any regional, disease-related deficit of afferent GABAergic terminals, as assessed by synaptosomal high-affinity [3H]GABA uptake. On a number of indices, it appears most likely that the data reflect both a loss of receptor sites, and a change in the population of receptor sub-types.

Adult↗

PubMed1996

Improved selectivity and sensitivity in the visualization of neurofibrillary tangles, plaques and neuropil threads.

Stain sensitivity is a key factor in estimating the frequency of plaques and neurofibrillary tangles in Alzheimer's disease (AD), making it essential that the sensitivity and selectivity of detection methods for identifying these lesions is maximized. Several new, improved techniques have recently been described, although these methods have not been compared quantitatively with those techniques currently recommended for use in standardized diagnostic protocols. In the present study, eight different stains were examined for their selectivity and sensitivity in detecting plaques and tangles in serial tissue sections from AD and control brains. Techniques compared were immunohistochemistry for tau and beta-amyloid, thioflavin S, nickel peroxidase method, and four silver impregnation techniques (Gallyas silver iodide, Campbell-Switzer-Martin, Garvey's modified Bielschowsky and methenamine silver methods). Among these eight staining techniques, the nickel peroxidase proved the most reliable method for the demonstration of the histopathological lesions of AD. This method labels all morphological types of plaques and tangles within a single tissue section, and provides several advantages for the analysis of lesion progression and distribution.

Aged↗

PubMed1996

Neuropathology of thiamine deficiency disorders.

The Wernicke-Korsakoff syndrome (WKS) is the most frequently encountered manifestation of thiamine deficiency in Western society. It is commonly seen in alcoholic patients, but may also occur in patients with impaired nutrition from other causes, such as those with gastrointestinal disease or AIDS. The pathology is restricted to the central nervous system and is characterised by neuronal loss, gliosis and vascular damage in regions surrounding the third and fourth ventricles and the cerebral aqueduct. In addition to WKS, thiamine deficiency may also result in beriberi, a cardiac and peripheral nervous system disease, and it has been implicated in the pathogenesis of cerebellar degeneration and peripheral neuropathy. Thus thiamine deficiency results in significant nervous system pathology and vigilance should be maintained in the diagnosis and treatment of this readily preventable cause of disease.

Animals↗

PubMed1996

Chronic alcoholism in the absence of Wernicke-Korsakoff syndrome and cirrhosis does not result in the loss of serotonergic neurons from the median raphe nucleus.

Previous studies have identified alcohol, thiamine deficiency and liver disease as contributing to the neuropathology of alcohol-related brain damage. In order to examine the effects of alcohol toxicity and thiamine deficiency on serotonergic neurons in the median raphe nucleus (MnR), alcoholic and previously published Wernicke-Korsakoff syndrome (WKS) cases without liver disease, were compared with age-matched non-alcoholic controls. While there was no difference between the estimated number of serotonergic neurons in either controls or alcoholics without WKS (means of 63,010 +/- 8,900 and 59,560 +/- 8,010 respectively), a substantial loss of serotonergic neurons was previously found in WKS cases (mean of 19,050 +/- 13,140). Further analysis revealed a significant difference in the maximum daily alcohol consumption between these groups. However, analysis of covariance showed that the number or serotonergic neurons in the MnR did not correlate with the amount of alcohol consumed. Therefore, our results suggest that cell loss in the MnR can be attributed to thiamine deficiency rather than alcohol per se.

Adult↗

PubMed1996

Loss of vasopressin-immunoreactive neurons in alcoholics is dose-related and time-dependent.

The chronic consumption of alcohol significantly reduces the number of vasopressin-producing neurons in the rat supraoptic nucleus [Maderia et al. (1993) Neourscience 56, 657-672] suggesting this region is particularly vulnerable to alcohol neurotoxicity. As hypothalamic vasopressin producing neurons are necessary for fluid homeostasis, it is important to assess if similar changes occur in humans. We analysed arginine vasopressin-immunoreactive neurons in the magnocellular hypothalamic nuclei of ten chronic alcoholic men (consuming > 80 g of ethanol per day) and four age- and sex-matched controls (consuming < 10g of ethanol per day). Brains were collected at autopsy and fixed in formalin. Serial 50 mu m-thick-sections of the hypothalamus were stained and assessed. The volume of the paraventricular and supraoptic nuclei and number of neurons were estimated using Cavalieri's principle and the optical dissector technique. The volume of these nuclei significantly correlated with the number of neurons and the number of vasopressin-immunoreactive neurons, and these measures significantly correlated with the maximum daily intake of alcohol. There was a loss of neurons at consumption levels greater than 100 g of ethanol per day, principally affecting the supraoptic nucleus although neuron loss also occurred in the paraventricular nucleus in cases with long histories of alcohol consumption. These results indicate that chronic alcohol consumption is toxic to hypothalamic vasopressin-producing neurons in a concentration- and time-dependent manner. As these magnocellular neurons are osmo-receptive, neuronal loss may result in fluid imbalances.

Adult↗

PubMed1996

Chronic alcoholics without Wernicke-Korsakoff syndrome or cirrhosis do not lose serotonergic neurons in the dorsal raphe nucleus.

Despite the considerable evidence that alcoholics have perturbation of serotonergic function, there is little pathological evidence for alcohol directly affecting the nervous system. The present study aims to assess neuronal loss that occurs as a consequence of alcohol neurotoxicity in the serotonergic dorsal raphe nucleus (DRN). To that end, the brains of eight alcoholics and eight age-matched control cases were carefully screened to eliminate serious liver disease, the sequela of thiamine deficiency, Wernicke-Korsakoff syndrome (WKS), and other pathological abnormalities. Brains were formalin-fixed for 2 weeks, cut, and then immunohistochemically stained using a monoclonal PH8 antibody specific for the rate-limiting enzyme of serotonin synthesis, tryptophan hydroxylase. The morphology of the serotonin-synthesizing neurons and their average size was similar in all cases. However, there was a reduction in the staining intensity of the reaction product in the DRN serotonergic neurons of most alcoholics. Neuronal counts on spaced serial sections revealed that there were an estimated average total of 106,100 +/- 19,500 serotonergic neurons in the DRN of alcoholics and 108,300 +/- 11,800 in the DRN of controls, indicating that in most alcoholics there is no reduction in the number of these neurons. Therefore, the effect of chronic alcohol consumption on the serotonergic system, in the absence of WKS or liver disease, seems to be functional rather than neuropathological.

Aged↗

PubMed1996

Reproducible sampling regimen for specific cortical regions: application to speech-associated areas.

The variability in the external gyri pattern of human brains has made the identification of specific cortical areas difficult. Studies correlating cortical structure and function have not consistently controlled for this variability. The aim of the present study was to develop a reliable and reproducible regimen for sampling five speech-associated and one non-speech associated cortical region in the human brain. The gyri of interest were labelled using non-aqueous dye prior to coronal slicing of brains at 3 mm intervals. Using the labelled gyri, a set of internal brain landmarks was established to aid in sampling one block of each cortical region of interest. The position of each internal landmark was determined as a percentage of the total brain length and breadth. The variability in the position of each internal landmark was investigated using analysis of variance and found to be consistent in three dimensions in all cases. The correlation of the sampled cortical region to the internal landmark was consistent in different cases with point to point agreement of 100%. This contrasts with the variability between cases in external gyri features. The sampled region was tested to determine cytoarchitectural variability by measuring the depth of each cortical layer. This technique found that the same cytoarchitectural regions were sampled in each case. As expected, these regions were distinguishable by the significant difference in the depth of different cortical layers. Accurate identification of both the external gyri and internal landmarks occurred with interrater point to point agreement of 90-100%.

Adolescent↗

PubMed1995

The contribution of alcohol, thiamine deficiency and cirrhosis of the liver to cerebral cortical damage in alcoholics.

The relative roles of alcohol toxicity, thiamine deficiency and cirrhosis of the liver in the pathogenesis of alcohol-related brain damage are unclear. Brain shrinkage and neuronal loss from four regions of the cortex was determined in 22 alcoholics with the Wernicke-Korsakoff Syndrome (WKS), cirrhosis of the liver or neither of these complications and compared to 22 age-matched non-alcoholic controls. Brain shrinkage was most marked in those alcoholics with WKS. Neuronal loss occurred only from the superior cortex and was of equal magnitude in all alcoholic subgroups. In an animal model of alcohol abuse and thiamine deficiency, neuronal loss from the cerebral cortex occurred in a time-dependent manner. Furthermore, those cells which contained the calcium-binding protein parvalbumin appeared to be preferentially damaged in this model.

Alcoholism↗

PubMed1993

Neuronal changes in the cerebral cortex of the rat following alcohol treatment and thiamin deficiency.

The contribution of thiamin deficiency to the pathology of alcohol-related brain damage is still unclear. This study used a model of prolonged alcohol abuse in which animals were subjected to a brief period of mild thiamin deficiency. The episode of thiamin deficiency was early (after 4 weeks), in the middle (after 15 weeks) or late (after 26 weeks) in their 28 week alcohol treatment period. A control group of animals fed no alcohol and maintained on a thiamin-replete diet was used for comparison. The brains were removed and sectioned in the coronal plane at 50 microns intervals. Successive serial sections were stained with cresyl violet for Niss1 substance and immunohistochemically with antibodies to the calcium-binding proteins parvalbumin and calbindin. These calcium-binding proteins identify the majority of GABA-containing neurons in the cerebral cortex. The number of cells in the Fr1 region of the cerebral cortex was quantitated. A significant loss of Niss1-stained neurons was identified from the early group, while a loss of parvalbumin-immunoreactive neurons was seen in the early and middle groups. No loss of neurons was identified from the late group. In addition, no loss of calbindin-immunoreactive neurons was seen. This study represents the first report of cortical neuronal loss in an animal model of alcohol abuse and thiamin deficiency. Moreover, the results imply that thiamin deficiency is integrally involved in the pathogenesis of alcohol-related cortical neuronal loss.

Alcoholism↗

PubMed1993

Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff syndrome.

Chronic alcoholism results in thiamine deficiency as a consequence of poor nutrition, impaired absorption, and decreased phosphorylation to the enzyme cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study demonstrate significant reductions of TPP-dependent enzymes [pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and transketolase] in autopsied cerebellar vermis samples from alcoholic patients with the clinical and neuropathologically confirmed diagnosis of Wernicke-Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics without WKS were within normal limits and activities of a nonthiamine-dependent enzyme, glutamate dehydrogenase, were not significantly different from control values in brain samples from alcoholics with or without WKS. These findings provide evidence, for the first time, of a direct implication of TPP-related metabolic processes in the pathogenesis of WKS. Decreased activities of alpha KGDH could be the trigger for a sequence of metabolic events resulting in energy compromise, and ultimately neuronal death in this syndrome.

Adult↗