Clinical and pathophysiologic aspects of viral infections of the CNS

The available defensive mechanisms are generally sufficient to protect the central nervous system (CNS) against the penetration of infectious particles. The blood-brain-barrier plays a decisive role in this process. The present paper represents the most important circumstances realizing that: 1. The macrophage-lymphocyte-system, 2. the "oligoclonal-CSF-IgG-reaction", and 3. the influence of psychological and physiological burdens on clinical-chemical or immunological parameters. It seems to be important to overcome the instability of the immunosystem and to reestablish the base-line.     

Activity-Dependent Activation of TrkB Neurotrophin Receptors in the Adult CNS

In this paper we have investigated the hypothesis that neural activity causes rapid activation of TrkB neurotrophin receptors in the adult mammalian CNS. These studies demonstrate that kainic acid-induced seizures led to a rapid and transient activation of TrkB receptors in the cortex. Subcellular fractionation demonstrated that these activated Trk receptors were preferentially enriched in the synaptosomal membrane fraction that also contained postsynaptic glutamate receptors. The fast activation of synaptic TrkB receptors could be duplicated in isolated cortical synaptosomes with KCl, presumably as a consequence of depolarization-induced BDNF release. Importantly, TrkB activation was also observed following pharmacological activation of brain-stem noradrenergic neurons, which synthesize and anterogradely transport BDNF; treatment with yohimbine led to activation of cortical TrkB receptors within 30 min. Pharmacological blockade of the postsynaptic α1-adrenergic receptors with prazosin only partially inhibited this effect, suggesting that the TrkB activation was partially due to a direct effect on postsynaptic cortical neurons. Together, these data support the hypothesis that activity causes release of BDNF from presynaptic terminals, resulting in a rapid activation of postsynaptic TrkB receptors. This activity-dependent TrkB activation could play a major role in morphological growth and remodelling in both the developing and mature nervous systems.     

Angiitis of the CNS (and the problem of its classification)]

The author deals with the different and partially divergent aspects of the classification of inflammatory vascular processes with particular reference to cerebrospinal involvement and forms. The limited pathomorphic tissue reaction of vessel wall elements and blood cells to different etiopathogenetic factors and the different cellular tissue structures observed for similar noxae are especially worth mentioning in this context. Also pointed out by the author in his present paper are the limitations of diagnosis. Central-nervous-system involvement usually brings with it special topographic difficulties and problems.     

A note on E. B. Titchener and G. M. Whipple

In 1898, one of E. B. Titchener's graduate students, Stella E. Sharp, conducted an experiment on Alfred Binet and Victor Henri's theory and belief that mental abilities should be tested by means of complex mental processes. Her subjects were seven advanced students in psychology. She concluded that the findings were incommensurate with the effort required. That closed the subject as an area of research and instruction in the Cornell Department of Psychology until 1941, when the subject of test theory and uses was included in that department's course offerings. This continued until 1963. Currently, the subject is once again being actively pursued in the Department of Education.     

APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to model Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.     

Relations between mechanisms of CNS arousal and mechanisms of stress

In the centennial year of the birth of Hans Selye, this review compares his classical concepts of stress with a modern approach to mechanisms of CNS arousal. Relations between the two concepts are described. Neuroanatomical, neurophysiological, and functional genomic mechanisms underlying CNS arousal are briefly reviewed. Controls over stress responses and arousal are compared to particular concepts of control system engineering. Understanding these two systems is of crucial importance because their dysregulation is associated with large numbers of disease states.     

Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment

Nutritional deficiencies are commonplace in patients with human immunodeficiency virus type 1 (HIV-1) infection, and recent research has indicated that nutritional factors may play an important role in the pathogenesis of HIV-1 disease. Although nutritional deficiencies are unlikely to be the primary causative factor in disease progression, they may contribute to cognitive dysfunction, neurologic abnormalities, mood disturbance, and immune dysregulation associated with HIV-1 infection. Furthermore, deficiencies of specific micronutrients have been associated with increased risk of HIV-1-associated mortality. This article will briefly summarize the role of macronutrient deficiency, the interactions of specific micronutrient deficiencies with neuropsychiatric functioning, and the role of these factors in HIV-1 disease progression. Since recent research has shown that normalization of many nutritional deficits and supplementation beyond normal levels are associated with improvements in neuropsychiatric functioning, potential treatment implications will also be discussed.     

Blood glucose and brain function: interactions with CNS cholinergic systems

We recently found that glucose injections attenuate amnesia and hyperactivity produced by scopolamine, a muscarinic antagonist. The present study examined whether glucose would augment behavioral effects produced by a muscarinic agonist, physostigmine. In experiment I, doses were first determined for which neither glucose (10 mg/kg) nor physostigmine (0.05 mg/kg) altered scopolamine-induced hyperactivity. However, combined glucose-physostigmine injections significantly reduced scopolamine hyperactivity. Experiment II evaluated the effects of glucose on physostigmine-induced tremors. Glucose (10, 100, and 250 mg/kg) or saline injections were given 20 min before physostigmine injections (0.4 or 0.05 mg/kg). Observations of glucose effects on the severity of physostigmine-induced tremors were then obtained at 5-min intervals for 25 min after physostigmine injections. Glucose (100 mg/kg) significantly facilitated the onset of tremors when injected before either dose of physostigmine, and augmented (at 100 and 250 mg/kg) tremor severity when injected before the lower dose of physostigmine. These findings indicate that glucose can facilitate the actions of a cholinergic agonist on two behaviors, locomotor activity and tremors, adding support to the view that circulating glucose levels can modulate central cholinergic function. More generally, the results provide additional evidence that circulating glucose levels can influence brain function.     

Glutamate as a transmitter in the CNS and its presumed significance in the pathogenesis of cerebral seizure forms--recent aspects

Glutamate is believed to be quantitatively the most outstanding of the excitatory transmitters in the CNS. Certain conformationally related analogues, e. g. kainate, N-methyl-D-aspartate, ibotenate, and homocysteate, act as glutamate agonists. The local or systemic administration of these "excitotoxic" compounds induces epileptiform activity pointing out new and deeper insights into the epileptic process. Additionally, the glutamate transmitter hypothesis is expected to give a chance of a causal comprehension for choreatic processes as well as for the mode of action of anticonvulsant and antispastic agents.     

Development of current problems regarding perinatal CNS lesions from a neuropathologic viewpoint]

Perinatal central-nervous-system lesions may be found in as many as one third of all subjects who died before, during, or after the time of birth. Today, hypoxia is considered to be an essential cause of such lesions; in contrast to views held previously, birth trauma, i.e., physical injury to an infant during its delivery, is of minor pathogenetic importance. Neurohistological studies showed that it is especially prolonged hypoxia - in addition to cerebral hemorrhage, damage to the cerebral parenchyma and medullary substance - which can cause lesion of the brain stem. A relatively frequent occurrence are isolated ischemic cerebrospinal nerve cell lesions. Their prognostic dignity in regard to the possible formation of synapses and the problem of damage to the neuroglia are as yet imperfectly understood.     

Feasibility of Conducting Long-Term Follow-Up of Children and Infants Treated for CNS Tumors on the Same Cooperative Group Clinical Trial Protocol

Given the barriers to conducting long-term assessment of neurocognitive and psychosocial functioning of those treated in infancy for central nervous system (CNS) tumors, a multi-site feasibility study was conducted. The primary objective was to demonstrate that it is feasible to identify, locate and assess the functioning of children treated on the same protocol 10-years post-treatment. Six sites obtained institutional approval, identified and recruited subjects, and obtained comprehensive neurocognitive and psychosocial data. All feasibility objectives were met. Barriers to participation included length of time for Institutional Review Board submission and review, clinical demands, limited eligible participants at individual institutions, difficulty locating long-term subjects and stipend/reimbursement concerns. Results indicate that long-term studies are feasible and essential given the need to address long-term issues of children treated at a young age for CNS tumors, especially as they relate to later academic and vocational planning, but require significant coordination and commitment of cooperative group and institutional resources.     

Linguistic and nonlinguistic impairments in writing: a comparison of patients with focal and multifocal CNS disorders

The hypothesis that the language disorder in Alzheimer's disease (AD) depends on degenerative brain changes in classical left-hemisphere language zones was tested by comparing the written language performances of a group of AD patients with mild-moderate dementia and left-hemisphere stroke patients with equally severe naming and auditory comprehension deficits who were in varying stages of recovery from Wernicke's aphasia. The results indicated significant qualitative group differences in performances between tasks and in errors within tasks. The findings are consistent with hypothesized disruption of more diffusely organized neurolinguistic systems in AD. The hypothesis that the language disorder in AD represents an exaggeration of the pattern of language change in normal aging was also examined by comparing the performances of AD patients to the changes that occur with very advanced normal aging. The data indicate convergence between AD and very elderly healthy subjects in some aspects of written language production.     

浅谈恙虫病的几点认识

恙虫病是自然疫源性急性传染病.通过恙虫病医疗实践,谈几点个人认识:恙虫病流行与该疫源地区鼠类活动有关;恙虫病疫源地会因气候变化而变更;重视恙虫病准确而及时诊断,尽量减少病人疾苦;恙虫病立克次体对人单核-吞噬细胞系统有特别的亲嗜性与专性细胞内寄生,是其临床病理基础;用氯霉素联合双黄连治疗恙虫病可获满意效果.     

Motor sequence learning performance in Parkinson's disease patients depends on the stage of disease

It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two different sequences in short succession. Results revealed that the PD patients were able to acquire two sequences in short succession but needed more time than healthy subjects. However, both the severity of axial manifestations, as assessed on a subsection of the Unified Parkinson's Disease Rating Scale III (UPDRS III) and the Hoehn and Yahr score, and the levodopa-equivalent dose (LED) were negatively correlated with the sequence learning performance. These findings indicate that, although PD patients are able to learn two sequences in short succession, they need more time and their overall sequence learning performance is strongly correlated with the stage of disease.     

Fingarette on the disease concept of alcoholism

Herbert Fingarette [1] argues that alcoholism is not a disease and that the alleged alcoholic under certain circumstances has the power to control his or her drinking disorders. I shall analyze Fingarette's argument and show that his position rests on some logical and conceptual confusions. In analyzing Fingarette's argument for the self-control theory of drinking disorders I conclude that it is problematic for the following reasons: (1) his argument assumes that the identification of a single cause of alcoholism is a necessary condition of its being a disease; (2) unless it is already assumed (a priori) that persons with drinking disorders possess freedom and self-control to the extent that Fingarette assumes they do, then such persons are likely to suffer from apathy or defeatism regarding their condition; (3) even if Fingarette is correct in his criticism of certain health care programs for those with drinking disorders, it does not follow from this that certain theories about the possible causes of such disorders are false; (4) Fingarette's claim that those with drinking disorders are morally responsible for their actions that result from their disorders is problematic, that is, unless it can be shown that such persons act freely; and (5) Fingarette attempts to support the self-control theory of alcoholism by refuting a ‘straw man’ conception of the disease model of alcoholism.     

浅谈恙虫病的几点认识

恙虫病是自然疫源性急性传染病。通过恙虫病医疗实践,谈几点个人认识：恙虫病流行与该疫源地区鼠类活动有关;恙虫病疫源地会因气候变化而变更;重视恙虫病准确而及时诊断,尽量减少病人疾苦;恙虫病立克次体对人单核-吞噬细胞系统有特别的亲嗜性与专性细胞内寄生,是其临床病理基础;用氯霉素联合双黄连治疗恙虫病可获满意效果。