[Are psychiatric diseases brain diseases?].
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Nearly a century after the seminal contributions of Emil Kraepelin, the search for neuropathologic correlates of schizophrenic psychoses continues. A multitude of neuroanatomic and neurochemical findings has emerged in recent years, but many of these findings are not replicated or are difficult to interpret in light of methodologic problems. In this review replicated neuropathologic and neuroimaging studies are discussed. The hypothesis that emerges from these studies is that schizophrenia is a developmental abnormality affecting the connectivity of the prefrontal and medial temporal cortices.
Rapid, accurate diagnosis and successful implementation of new stroke therapies will depend on the refinement and skilled use of neuroimaging. Because a variety of MR techniques offer information on local brain biochemistry, blood flow, perfusion, vascular integrity, ischemia, edema or free water, infarction, and hemorrhage, there is intense interest in their application to cerebrovascular disease. This review highlights recent advances in MR technology as they relate to conventional MR imaging, MR angiography, and basic MR research into the use of diffusion, perfusion, and spectroscopic techniques.
Brain vascular diseases are ranked the third as the cause of morbidity and mortality in majority of the countries of the world. In about 80% of the cases of vascular brain diseases, it is ischemic brain disease (IBD). Atherosclerosis of main cerebral arteries is most frequently responsible for the occurrence and development of IBD. In recent years it was reported for the first time of the association of atherosclerosis and/or its complications and proteinuria. Assuming that there exists the significant association between the degree of proteinuria and clinical parameters of IBD, the aim of this study was to investigate the frequency and patterns of the association of proteinuria and clinical IBD parameters. The study was performed in 180 patients with IBD of atherothrombotic origin and 60 patients with the diseases of non-vascular origin, as the control group. In all patients quantitative determination of proteinuria was performed, and in the patients with IBD was determined the degree of IBD and afterwards the degree of functional and neurologic impairment prior to and at the end of treatment in acute phase using the standardized scales. The results of the study revealed the existence of significant frequency of proteinuria in the patients with IBD, as well as the significant association between the degree of proteinuria and severity of IBD. It was concluded that proteinuria in patients with IBD was probably associated with the atherogenic processes and physiopathologic processes of IBD, respectively, which could have predictive value for the outcome of the disease in the early stage.
As a process of rational enquiry into an empirical field, psychiatry must submit itself to the same discipline as other areas of science. Effectively, it must show that its fundamental premises are both internally and externally consistent, and that its methods of investigation satisfy prevailing criteria of scientific methodology. When psychoanalytic psychology (and hence all psychodynamic models) and behaviourism were analysed from these points of view, they were found wanting. To date, there has been little or no meta-analysis of the third great school of psychiatric theorizing, biological psychiatry. A preliminary analysis establishes sharp limits to the notion that biological psychiatry is the "wave of the future". Like psychoanalysis and behaviourism, it cannot form the basis of a general theory of psychiatry. Since it lacks an adequate theoretical framework, the inescapable conclusion is that psychiatry is nothing more than protoscience.
To study the incidence of coronary heart disease (CHD), cerebrovascular diseases (CVD), combined pathology (CHD and CVD), and their risk factors such as arterial hypertension (AH), overweight (OW), hypercholesterolemia (HC), and tobacco smoking in the same population, a random representative sample of male and female populations were examined in three districts of Novosibirsk. AH and tobacco smoking were found predominant among men, whereas OW and HC among women. It turned out that almost every fourth person out of the men and almost every second woman suffered from cardiovascular diseases. In the men, the CHD/CVD ratio was 1:1, that in the women, was 1:7. In the men and women, suffering from combined pathology, AH occurred more frequently as compared to those with CHD or CVD alone. OW promoted the development of CVD and combined pathology in women to a greater degree, whereas HC favoured the development of CHD and CVD in men.
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Ischemic brain disease (IBD) represents clinical entity participating with almost 80% in all vascular brain diseases. Ethiopatogenesis and pathophysiology of the ischemic brain disease are apparently most complex in human medicine. In addition to the significant progression in understanding of ethiopatogenesis and pathophysiology of the ischemic brain disease, we are currently aware of the fact that in one third of these patients the source--the disorder or the disease of crucial importance for this sequence of events in the opposing direction cannot be diagnosed with certainty. This case report presents a 32-year-old patient with the verified ischemic lesion of brain parenchyma, in whom the lowered concentrations of protein S were registered by comprehensive clinical and biochemical examinations. The lower concentrations of protein S are a significant co-factor of anticoagulant system, in the absence of other significant diseases, disorders or abnormalities which could ethiopatogenetically be significant for IBD.
Fourteen patients and five healthy individuals underwent magnetic resonance (MR) imaging to determine an effective multiple spin echo pulse sequence for estimating T2. Lesions examined included infarction, glioma, multiple sclerosis, and acute hematoma. A pulse repetition time (TR) of 1,500 msec and echo delays (TEs) of 25, 50, 75, and 100 msec were used. Computed T2 images were derived from all four echoes, the first two echoes, and the first and fourth echoes. T2 values were obtained from specific brain locales using region-of-interest analysis. Use of either the first two echoes or the first and fourth in the T2 fit provided T2 estimates which closely correlated with that of the four-echo analysis. The noise level in T2 maps constructed from the 25- and 100-msec echoes was modestly (typically 10%) higher than that from four echoes; noise level from the 25- and 50-msec echoes was markedly higher, typically 60%. This behavior is remarkably consistent with that predicted from theory. All 19 subjects displayed consistent relative T2 values for specific brain structures; in 13, the absolute T2 values fell within a limited range. Despite the high sensitivity of T2 images, their specificity in the detection of most brain disease appears limited except in acute intracerebral hematoma, which exhibited a decreased T2 relaxation time using high-field-strength MR imaging.
Bcl-2 protein has been suggested to be one of the proteins preventing apoptosis in a variety of cell types. Recently, apoptosis has been suggested to have an important role in the pathogenesis of Alzheimer's disease (AD). We have utilized Bcl-2 immunohistochemical methods to examine Bcl-2 in the hippocampus and entorhinal cortex of AD patients ranging in clinical and neuropathological severity from mild to severe and compared these results to those obtained from age-matched controls. Immunoreactivity for Bcl-2 was predominantly found within neurons. Bcl-2 immunostaining within AD tissue was increased relative to controls in most neurons of the entorhinal cortex, subiculum, CA1, CA2, CA3, hilus and dentate gyrus. Relative Bcl-2 staining increased in parallel with increasing disease severity. However, neurons exhibiting immunoreactivity for markers of neurofibrillary tangle formation (AT8 and PHF-1) showed reduced Bcl-2 staining, suggesting that Bcl-2 may be down regulated in these degenerating neurons. Bcl-2 immunoreactivity within astrocytes and the vasculature was also increased in AD. These results suggest that Bcl-2 protein may have a role in compensation responses to AD pathology, perhaps affording to the remaining neurons a margin of protection from apoptosis.
The binding of cocaine and cocaethylene to homogenates of both normal whole brain and whole brain with Alzheimer disease patients (Alzheimer brain) was investigated in vitro using equilibrium dialysis of the unlabelled drugs at 4 degrees C. Two binders of cocaine were characterized in normal brain (binder 1: Ka, 5.73 x 10(3) L/mol; Bo, 7.44 x 10(-5) mol/L) (binder 2: Ka, 1.54 x 10(3) L/mol; Bo, 2.50 x 10(-4) mol/L) and in Alzheimer brain (binder 1: Ka, 3.08 x 10(2) L/mol; Bo, 6.66 x 10(-4) mol/L) (binder 2: Ka, 8.74 x 10(1) L/mol; Bo, 4.30 x 10(-3) mol/L). For cocaethylene three binders were noted in normal brain (binder 1: Ka, 3.23 x 10(3) L/mol; Bo, 1.22 x 10(-4) mol/L) (binder 2: Ka, 3.10 x 10(3) L/mol; Bo, 2.01 x 10(-4) mol/L) (binder 3: Ka, 1.63 x 10(3) L/mol; Bo, 3.59 x 10(-4) mol/L) and two binders in Alzheimer brain (binder 1: Ka, 5.18 x 10(3) L/mol; Bo, 3.06 x 10(-5) mol/L) (binder 2: Ka, 3.36 x 10(3) L/mol; Bo, 7.75 x 10(-5) mol/L). The binding of cocaine to normal brain was much stronger than to Alzheimer brain (ten- to 100-fold), whereas the binding of cocaethylene was similar in normal and Alzheimer brain. Cocaine and cocaethylene binding to human brain was compared with cocaine and cocaethylene binding to other human tissues previously studied by this laboratory.
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Nuclear brain imaging is able to show functional abnormalities of lesions that are not detectable by CT and MR images. The diagnostic keys of nuclear-imaging in terms of clinical usefulness are its early detection of lesions and determination of the efficacy of drug and surgical therapies. In dementic patients, F-18 FDG brain images can be diagnosed as Alzheimer's disease 12 months earlier than is possible on CT and MRI images, and can provide information for effective drug therapy. O-15 water CBF images can predict the effect of Nicholin by assessing transient increases in cerebral blood flow (CBF), thereby facilitating improvement in higher brain functions such as orientation. In stroke patients, brain SPECT images with Tc-99m HMPAO can predict fatal cerebral hemorrhage caused by anti-thrombic therapy by showing the decrease in count ratio (count ratio of infarcted to contralateral area of < 0.34) in the acute phase and identifying disruption of the blood brain barrier by showing hyperfixation in the subacute phase. Brain SPECT with I-123 IMP can also identify "misery" perfused areas resulting from reduced CBF and decreased vasoreactivity in the chronic phase. This criterion is utilized for patient selection for extracranial/intracranial bypass surgery, because patients with areas of poor perfusion might be indicated for such surgery. Since nuclear medicine images can accurately select candidates for drug or surgical therapies, they will be beneficial in reducing Medicare costs as well as in enhancing patients' quality of life as a result of the successful treatment. With the advancement of technology, nuclear medicine units that can simultaneously obtain CT images and can combine functional with anatomical images will provide more useful information for the diagnosis of brain disease.
25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double isotope imaging technique using 99mTcO4- and 99mTc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. 99mTc-EHDP is shown to be the tracer of choice for the imaging of CVA's and 99mTcO4- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.
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To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.
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