High pressure-low flow remodeling of the rat saphenous vein wall.

Objective To better understand factors that may play a role in the development of varicosities. Methods We induced combined flow-pressure disturbance in the saphenous system of the rat by performing chronic partial clipping of the main branch. Biomechanical and quantitative histological testing was undertaken. Results A rich microvenous network developed. Bloodflow decreased to 0.65 ± 0.18 µl/s (control side, 3.5 ± 1.4 µl/s) and pressure elevated to 6.8 ± 0.7 mmHg (control side, 2.3 ± 0.2 mmHg, p < 0.05). Involution of the wall and lumen was observed (16.5%, 28.7% and 35.5% reduction in outer diameter, wall thickness and wall mass respectively, p < 0.05). Elevated macrophage (CD68) and cell division (Ki67) activity was observed. Elastic tissue and smooth muscle actin became less concentrated in the inner medial layers. Conclusions Low-flow induced morphological shrinking of the lumen in veins may override pressure-induced morphological distension. Loosening of the force-bearing elements during flow-induced wall remodeling may be an important pathological component in varicosity.

[Relapse and insomnia in unipolar major depression]. / Recidíva és inszomnia unipoláris depresszióban.

The connection between mood and sleep disorders is highly complex and can be studied and interpreted in many respects. Epidemiologic data show that the co-occurrence of the two disorders is quite frequent. Thus an approach regarding them as a unit promotes biological psychiatric research by revealing new pathophysiological and therapeutic conclusions. Chronobiological results related to mood disorders have recently been described in excellent reviews including Hungarian ones. In the present review, the necessity of treatment of sleep disorders is evaluated in the context of relapse/remission/recurrence. Scientific data suggest that patients with insomnia have a ten-fold risk of developing depression, and insomnia plays an important role in depression relapses, recurrence of depressive episodes and becoming depression chronic. From neurobiological point of view, mood and sleep disorders have many features in common. Research has revealed decreased levels of melatonin and advanced sleep phases (shifted earlier) in depression, and altered and imbalanced monoaminergic pathways, and REM abnormalities in sleep disorders. Some authors suggest that REM abnormalities disappear along with the mood improvement, and the sleep structure can completely restore after remission. However, persistent abnormalities of REM sleep and slow wave sleep have also been found in remission, which increased the risk of the relapse and recurrence. Recently, there is an agreement as to the early treatment of insomnia can prevent the development of mood abnormalities. Alterations of cascades related to neural plasticity can also be a link between sleep and mood disorders. Neural plasticity is closely related to learning, sleeping, and cortisol regulation (coping with stress), and this draws the attention to comorbidity with further disorders (anxiety, dementia).

Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann-Pick C patient.

Niemann-Pick disease type C is a rare lipid trafficking disorder characterized by the accumulation of cholesterol and glycosphingolipids in the brain and viscera. Perinatal, early infantile, late infantile, juvenile and adult forms are distinguished based on the age of manifestation. In the juvenile form, patients in their early years are usually, but not always, symptom free, but present with neurodegeneration later in their lives. These include clumsiness, ataxia, seizures, motor and intellectual decline. Psychiatric manifestations may occur at any stage of the disease. These manifestations include schizophrenia, presenile dementia, depression or psychosis. In 2009, miglustat was approved for the therapy of the disease. We present a case of a patient with juvenile Niemann-Pick C disease whose psychosis was reversed completely by miglustat treatment. Based on our clinical experience we suggest considering Niemann-Pick C in cases of therapy-resistant psychosis and encourage the introduction of miglustat in Niemann-Pick C patients even in the most advanced cases, with respect to psychiatric illness.

Susceptibility to interference and intrusion errors in consequence of the dominant hemisphere's hippocampal infarct: a case report.

We present a case of a man with an ischemic lesion of the left hippocampus. Detailed neuropsychological assessment revealed susceptibility to retroactive interference and a tendency to make intrusion errors in addition to mild deficits in the verbal memory processes. Although retroactive interference and intrusion errors are normally considered to be the manifestations of frontal lobe dysfunctions, the idea of susceptibility to interference has recently begun to emerge in the literature, as an explanation of medial temporal lobe amnesia. Our data support this new theory, suggesting that one role of the hippocampus is to decrease the interference during the learning processes.

Automated Neuropsychological Test Battery in depression -- preliminary data.

AIMS: Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in patients with major depressive disorder (MDD) during acute episode. However, limited data are available concerning whether these abnormalities persist in the remission phase. METHODS: In the present study CANTAB (Cambridge Automated Neuropsychological Test Battery) was used to evaluate the cognitive impairment associated with depression during acute episode and in remission. 25 patients with MDD during an acute episode and 11 patients also during remission were tested with CANTAB. RESULTS: During the acute episode, Delayed matching to sample, Paired associate learning, Spatial recognition memory, Rapid visual processing and Visuospatial planning were impaired. In remission the improvement of visual learning ability, spatial recognition memory, psychomotor speed, and executive function was observed. CONCLUSIONS: The results suggest that MDD is associated with neurocognitive dysfunctions in different domains, the most prominent deficit was found in the Paired associate learning test, which requires both the elaboration of "frontal strategies" and the "mnemonic processes". Cognitive impairment was found to improve partly in remission, suggesting that an individual's current mood interacts with the ability to perform a cognitive task. Besides these state markers, trait deficits are important because cognitive impairments which do not improve in remission might serve as endophenotypes of depression.

The message of the survival curves: I. Composite analysis of long-term treatment studies in bipolar disorder.

RATIONALE: There is a shortage of studies analyzing the time course of recurrent episodes and comparing effectiveness of long-term treatments in bipolar disorder. 'Number needed to treat' (NNT) analyses have been proven to be useful for clinically meaningful comparisons, but results vary considerably among studies. The survival curves of different trials also show a great variability preventing reliable conclusions on the time course of maintenance therapies. The variance of survival analyses on long-term medication management can be reduced with increasing the statistical power by combining the life-tables of individual studies. METHODS: In this study the survival tables of 28 studies on maintenance treatment of bipolar disorder were reconstructed from the published diagrams, and the numbers of relapsed patients in the original studies were estimated for plotting composite survival curves of an inactive, mono- and combination therapy arm. The review was finally based on 5231 subjects. RESULTS: The resulting composite diagrams indicate that within the first year 48% of patients on monotherapy, and 35% on combination therapy experienced recurrence of any affective episode ('early relapsers'). The rest of the patient population was affected by recurrences in a smaller rate over a more extended period of time ('late relapsers'). For a favorable outcome at 40 months of episode prevention in bipolar disorder the NNT was 6 for mono- and 3 for combination therapy. Log-rank analyses of the composite data supported the effectiveness of both medication protocols over placebo, and the superiority of drug combination over monotherapy; though there were some indications of decreased efficacy in the two treatment arms after extended maintenance. CONCLUSIONS: Composite analysis offers increased statistical power for studying the time course of survival data. Mood episodes in bipolar disorder are likely to recur early on and relapses in "real-life" can be more frequent than the rates published here. Our results favor combination therapy for the long-term management of bipolar disorder. Concerns are expressed that NNT analyses have significant limitations when applied to recurring events with cumulative deterioration instead of cases where cumulative improvement is expected over time.

[Maintenance therapy in schizophrenia -- a brief review of the literature]. / A szkizofrénia fenntartó gyógyszeres kezelése -- a szakirodalmi adatok rövid áttekintése.

This article reviews the role of the first and second generation antipsychotics in the long-term treatment of schizophrenia. The different forms of course, the relationship between maintenance treatment and relapse rates, the influence of depot antipsychotics and adherence on the outcome, and other predictive factors will be addressed in the paper. The necessity of a survival meta-analysis is emphasized for the calculation of the 'number needed to treat', and for a detailed analysis of the time course of recurrences.

Psychiatric symptoms of patients with primary mitochondrial DNA disorders.

BACKGROUND: The aim of our study was to assess psychiatric symptoms in patients with genetically proven primary mutation of the mitochondrial DNA. METHODS: 19 adults with known mitochondrial mutation (MT) have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI), the Symptom Check List-90-Revised (SCL-90-R), the Beck Depression Inventory-Short Form (BDI-SF), the Hamilton Depression Rating Scale (HDRS) and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II) As control, 10 patients with hereditary sensorimotor neuropathy (HN), harboring the peripheral myelin protein-22 (PMP22) mutation were examined with the same tools. RESULTS: The two groups did not differ significantly in gender, age or education. Mean HAQ-DI score was 0.82 in the MT (range: 0-1.625) and 0.71 in the HN group (range: 0-1.625). Level of disability between the two groups did not differ significantly (p = 0.6076). MT patients scored significantly higher on the BDI-SF and HDRS than HN patients (12.85 versus 4.40, p = 0.031, and 15.62 vs 7.30, p = 0.043, respectively). The Global Severity Index (GSI) of SCL-90-R also showed significant difference (1.44 vs 0.46, p = 0.013) as well as the subscales except for somatization. SCID-I interview yielded a variety of mood disorders in both groups. Eight MT patient (42%) had past, 6 (31%) had current, 5 (26%) had both past and current psychiatric diagnosis, yielding a lifetime prevalence of 9/19 (47%) in the MT group. In the HN group, 3 patients had both past and current diagnosis showing a lifetime prevalence of 3/10 (30%) in this group. SCID-II detected personality disorder in 8 MT cases (42%), yielding 3 avoidant, 2 obsessive-compulsive and 3 personality disorder not otherwise specified (NOS) diagnosis. No personality disorder was identified in the HN group. CONCLUSIONS: Clinicians should be aware of the high prevalence of psychiatric symptoms in patients with mitochondrial mutation which has both etiologic and therapeutic relevance.

[Changes in the brain with schizophrenia: postmortem findings]. / Posztmortem vizsgálatok eredményei a szkizofrénia kutatásban.

In this study morphological knowledge about schizophrenia including different levels from macroscopic to molecular changes is summarized. We have had data on the schizophrenic brain for more than 100 years. Cortical and subcortical regional grey matter volume and density decreases, as well white matter lesions are well-known phenomena. They induce disconnectivity which is a significant element in the pathology of schizophrenia. The most important detectable macroscopic changes are volume reductions in the temporal lobe, prefrontal cortex, superior temporalis gyrus, anterior cingulate gyrus and planum temporale. The later is also important in terms of the hemispheric asymmetry reduction, which is considered to be a relevant feature of the disease. Recently several macroscopic changes, mainly neuropil alterations, axonal and dendritic changes, and extensive functional and structural alterations of the synapses have been revealed. Although numerous mechanisms (aberrated migration, altered pruning and neuroplasticity) have already been identified in the background, a full picture has not yet emerged. Remarkable results have been collected concerning the energy metabolism in the brain, lipid metabolism, and proteomic results. At present there are controversial data concerning the association between the development of the above-mentioned alterations and antipsychotic medication.

[P300 in mild cognitive impairment and in dementia]. / P300 enyhe kognitív zavarban és demenciában.

OBJECTIVES: The late component of the event-related potential (ERP), P300 is a marker for cognitive brain functions. The objective of this study was to examine P300 parameters in dementia and in mild cognitive impairment (MCI), to examine whether there is a correlation between the changes in P300 parameters and the type and severity of dementia, and to determine P300 abnormalities in MCI in relation to the presence/absence of CT/MRI abnormalities. METHOD: Auditory event-related potentials, P300 were recorded in 28 MCI patients (14 of them with normal CT/MRI findings and 10 subjects with mild ventricular enlargement). In another group of patients, 31 demented patients were examined, of whom 17 patients were diagnosed with Alzheimer's dementia (AD), and 14 patients with vascular dementia (VD). Forty healthy volunteers served as the control group. RESULTS: Mean P300 latency was significantly increased for both demented patient-groups. We found that prolongation of P300 latency was correlated with the severity of dementia. Mean P300 amplitude was significantly decreased in both groups of demented patients. In MCI, the mean latency of P300 was significantly longer among patients with mild cerebral atrophy compared to control volunteers and no significant changes were found for MCI patients with normal CT/MRI findings. Mean P300 amplitude was decreased only in demented patients. CONCLUSIONS: The prolongation of P300 latency was significant among patients with both vascular and Alzheimer's dementia, and also among MCI patients with mild cerebral atrophy. The severity of dementia is positively correlated with P300 latency; however, this prolongation is independent of the type of dementia. The structural brain changes in MCI are related to P300 latency prolongation and thus may indicate an increased risk for developing dementia in MCI patients.

Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia.

The prevalence of Alzheimer's disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE(2) offers protection and apoE(3) is neutral, while apoE(4) promotes the development of the disease. Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD. Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates. In our results, we found that most of the patients with AD had the apoE(4) isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 +/- 0.89, VAD: 6.3 +/- 0.8, AD: 6.52 +/- 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 +/- 0.6, VAD: 3.96 +/- 0.8, AD: 3.84 +/- 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 +/- 55 U/l; AD: 131 +/- 37, VAD: 151 +/- 50 l; p < 0.05). Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimer's disease and vascular dementia.