bluuebunny/crossref_metadata_2025 huggingface dataset:
Mild Dementia Associated with Joseph Disease in a Japanese Family
Authors: Fukutani Yuken , Matsubara Rokuro , Katsukawa Kazuhiko , Kobayashi Katsuji , Nakamura Ichiro , Yamaguchi Nariyoshi
Published: August 2007

We clinically studied 4 patients with Joseph disease in a Japanese family, who developed mild dementia, and neuropathologically examined one autopsied case among them. Neurological findings included cerebellar ataxia, progressive external ophthalmoplegia, peripheral amyotrophy, and pyramidal signs. Mental state examination revealed mild impairment of intelligence. The dementia was characterized by mild memory disturbance with preservation of orientation, slowing of thought processes, affective changes including apathy and depression, impaired ability to manipulate acquired knowledge, and the absence of aphasia, apraxia and agnosia. CT demonstrated severe atrophy of the brain stem and severe dilatation of the fourth ventricle with mild atrophy of the cerebral and cerebellar hemispheres. EEG showed slowing of background activity. The autopsied case showed atrophy of the tegmentum of the brain stem in addition to the common pathological findings of Joseph disease. The features of dementia in the 4 patients were similar to those seen in ‘subcortical dementia’, suggesting that its pathological basis may be involvement of the tegmentum of the brain stem.
EEG Mapping in Dementia of the Alzheimer Type
Authors: Iznak A.F. , Chayanov N.V. , Gavrilova S.I. , Seleznyova N.D. , Kolykhalov I.V. , Mikhailova N.M. , Kalyn Ya.B.
Published: August 2007

EEG topography correlates of severity and type of Alzheimer type dementia (DAT) have been studied in 21 senile dementia (SD), and in 18 Alzheimer disease (AD) patients, as well as in 15 mentally normal elderly persons. EEG maps in SD and AD patients differed from that in normals by increase of theta-delta EEG spectral power, and by suppression of alpha band power, more pronounced in AD than in SD patients, especially, in the left hemisphere. AD and SD patients also showed different EEG topography dynamics with increase in degree of cognitive functions impairment assessed by MMSE. Results obtained are in good concordance with data on metabolism and local cerebral blood flow decrease, and on cognitive deficiencies in different clinical forms of DAT.
Protection from Oxygen Radical Damage in Human Diploid Fibroblasts by Acetyl-L-Carnitine
Authors: Tesco G. , Latorraca S. , Piersanti P. , Piacentini S. , Amaducci L. , Sorbi S.
Published: August 2007

Oxygen radical production is suspected of being a major cause of aging. We have studied the effect of acetyl-L-carnitine (ALC) on oxygen metabolites toxicity in fibroblast cell lines derived from skin biopsies taken from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde with 50 mU of xanthine oxidase (XO). We measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures, both 4 days preincubated with 50 µg/ml ALC and not treated, after a 2-hour XO incubation in order to quantify the cell damage. We found a significant increase of LDH activity in cells without ALC exposed to free radical formation. No significant increase of the LDH activity was observed in the same cell lines, in the same experimental conditions after 4 days’ preincubation with 50 µg/ml ALC.
Homicidal Behaviour in Elderly Patients Admitted to a Psychiatric Hospital
Authors: Ticehurst Stephen B. , Ryan Mark G. , Hughes Frank
Published: August 2007

Fourteen elderly psychiatric patients who attempted or committed homicide are described. Most were cognitively impaired. None were intoxicated despite many having histories of alcohol abuse. Few patients went to court, had a history of domestic violence or previous psychiatric treatment. The sole patient to complete homicide was the only patient who used a gun. None had attempted suicide. The frequency of neuropsychiatric symptomatology highlights the need for psychiatric assessment of elderly offenders.
Decreased Level of Creatine Kinase BB in the Frontal Cortex of Alzheimer Patients
Authors: Burbaeva G.Sh. , Aksenova M.V. , Makarenko I.G.
Published: August 2007

Complex immunochemical and immunocytochemical investigation of postmortem frontal cortex (area 10) of normal controls and Alzheimer disease (AD) patients revealed a decrease in immunoreactive creatine kinase BB (CK-BB) content in AD. This decrease was not the result of age, postmortem delay, psychotropic therapy or astrocytic destruction. In some AD cases CK-BB was found in neurofibrillary tangles. The possible reasons for these findings are discussed. The decrease of CK-BB level may be important in the pathogenesis of AD because of the consequent energy deficit.
Peptidases Are Affected Differently in Neocortical Regions of Brains from Patients with Alzheimer's Disease
Authors: Terwel Dirk , Markerink Marjanne , Jolles Jellemer
Published: August 2007

Although it is recognized that changes in protease activities may be involved in the etiology of pathological changes in the human brain, there have been few studies on normal and pathological protein catabolism. In the present study the activities of major cortical aminopeptidase and prolylendopeptidase were determined in frontal and medial temporal cortical samples of brains from patients with Alzheimer''s disease (AD) and control patients matched for age. Prolylendopeptidase activity was reduced by 45–50% in the frontal and medial temporal cortex of AD patients as compared with controls, whereas major aminopeptidase activity was unaltered. The possibility that the changes in peptidase activities in AD are age-dependent was studied in postmortem neocortical samples from 18 AD patients who had died between 55 and 90 years of age. Prolylendopeptidase activity was lower in patients who died at a relatively early age than in patients who died at a relatively old age. This underscores the notion that, with respect to age, there may be heterogeneity in neurochemical changes in AD.
The Role of Cholinergic Deficiency in Neuropsychological Deficits in Idiopathic Parkinson's Disease
Authors: Reid W.G.J. , Broe G.A. , Morris J.G.L. , Hely M.A. , Moss N.G. , Genge S.A. , O'Sullivan D.J. , Williamson P.M.
Published: August 2007

The study was designed to examine the effects of long-term anticholinergic therapy on neuropsychological functioning in a group of non-demented PD patients before and after treatment with benzhexol. Forty-two de novo patients with PD who were participants in a larger multicentre drug study were divided into two groups according to long treatment with and without an anticholinergic agent. There were 12 in the anticholinergic group. All patients were receiving treatment with either levodopa or bromocriptine or a combination of the two as their primary therapy. The patients were given a detailed neuropsychological assessment at baseline before commencing treatment. The assessment was repeated in phase 2 after 3 years of treatment. The groups were compared at baseline and at 3 years. Those patients treated with anticholinergics had significant impairment in their performance in an auditory verbal learning test compared to those treated with dopaminergic therapy alone. By contrast, their speed of retrieval of words from memory in a verbal fluency test significantly improved. Analysis of the serial position curve revealed that the anticholinergic group had impairment in the recency effect (short-term memory store). It is suggested that anticholinergics have a selective effect on sustained attention and effortful processing due to lesions in the ascending cholinergic neurons projecting to the frontal lobes. However, the improved verbal fluency with muscarinic blockade suggests a disinhibition or release phenomenon of certain frontal lobe functions due to deregulation of other non-cholinergic neurotransmitters projecting to the frontal lobes. It is suggested that treatment with anticholinergics thus serves to amplify the already compromised cholinergic system in PD and at the same time disinhibit possible catecholamine activity in the frontal lobes resulting in improvement in specific areas of frontal lobe function.
Cerebral Transit Time and Neuropsychiatric Symptoms in Patients with Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy
Authors: Hakola H.P.A. , Länsimies E. , Kuikka J.
Published: August 2007

Five patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) were examined clinically and using SPECT. The degree of dementia ranged from mild to severe. In the cases with severe dementia cerebral transit time (CTT) for each hemisphere was slightly increased (4.9 ± 0.5 s). In 2 cases with repeated study both clinical state and CTT deteriorated. Dynamic brain imaging was moderately abnormal in 2 patients with severe dementia. Static brain imaging was normal in all studies performed. The connections of SPECT findings to the pathogenesis of PLO-SL are discussed.
The Lupus Anticoagulant and Dementia in Non-SLE Patients
Authors: Inzelberg R. , Bornstein N.M. , Reider I. , Korczyn A.D.
Published: August 2007

The syndrome of circulating anticoagulants in patients without evidence of systemic lupus erythematosus (SLE) has lately become a focus of interest. The clinical features, neuroimaging findings and clinical course of 12 such patients, who presented with neurological symptoms, were analyzed. None of the patients fulfilled the American Rheumatism Association (ARA) criteria of SLE. During a follow-up period of up to 5 years, 9 patients (75%) deteriorated mentally. In 5, cerebrovascular lesions were observed clinically and/or neuroradiologically. Four patients showed slowly progressive mental decline without focal deficits on clinical examination or on CT and MR studies of the brain, except for a small cortical infarct in one case. All patients had radiological evidence of cortical atrophy. Thus, dementia may be a prominent feature among patients with the lupus anticoagulant. Possible underlying mechanisms, such as multi-infarct state, as well as an autoimmune process affecting specifically CNS structures, are discussed.
Prevalence of Dementia amongst Elderly Japanese with Leprosy: Apparent Effect of Chronic Drug Therapy
Authors: McGeer Patrick L. , Harada Nobuo , Kimura Hiroshi , McGeer Edith G. , Schulzer Michael
Published: August 2007

The overall prevalence of dementia in 1,410 Japanese leprosy patients 65 years or over continuously treated with dapsone or closely related drugs was 2.9%. This compares with 4.83% of 621 cases treated intermittently and 6.25 % of 1,761 cases untreated for at least 5 years. Multiple logistic regression analysis showed a highly significant increase of dementia with age (p = 0.0001) and, after age adjustment, a significant reduction of dementia in drug-treated compared with drug-free patients (p = 0.017). Such treatment had no significant effect on the prevalence of strokes. These data suggest that dapsone and closely related drugs may have potential use as antidementia agents.
On the Question of the Mental State of Centenarians
Authors: Powell Artiss L.
Published: August 2007

The number of individuals over age 100 years in the United States will increase from 25,000 in 1986 to more than 108,000 by the year 2000. Despite this expected growth there is almost no information about their intellectual function. This is unfortunate since the study of centenarians offers valuable insight into the effects of aging upon the central nervous system. It may also clarify whether Alzheimer''s disease represents premature aging. To better understand their mental state, I evaluated 20 centenarians (17 women and 3 men) with a mean age of 101.75 years. The group completed on average 6.6 years of education and each had 4 illnesses and took 3.5 prescribed drugs. Eighty percent were in nursing homes, mostly due to inadequate social supports. Caregivers had thought that the majority were not demented. During evaluation, 75% had impaired vision while half had disturbed hearing. The speed of thought and body movement were slowed significantly. Centenarians had poor awareness of their environment, in general (p = 0.0019) and had impaired judgement (p = 0.006). Additionally, only 3 individuals had a history and examination to suggest Alzheimer''s disease. Unfortunately, the Folstein Mini-Mental State Exam (MMSE) and the Washington University Clinical Dementia Rating (CDR) were often difficult to score. Mean scores for the MMSE of 7.5 (1 standard deviation, 7.134) and the CDR of 2.08 (1.07) suggested dementia. These observations suggest that impaired intellectual function may be common in this group but there are several limitations on evaluating and interpreting such data.
Depression in the Elderly
Authors: Rosenberg David R. , Wright Bruce , Gershon Samuel
Published: August 2007

This paper examines the clinical presentation of, the biochemical abnormalities associated with, and the treatment of depressive disorders in late life. A comparison of geriatric depression (late-onset, first-episode depression) will be made to depression as it presents in childhood and middle age. Childhood onset depression is now accepted as a valid diagnostic/clinical entity. However, there is no conclusive evidence to date that pharmacologic intervention is effective in the treatment of childhood onset depressive disorder. On the other hand, major depression occurring in middle age has been shown to be quite responsive to pharmacologic interventions. Although the precise mechanism of pharmacologic intervention is unknown, certain biochemical abnormalities have been associated with middle-age onset of depression. We will discuss the similarities and differences of depression in the elderly to depression in both middle age and childhood. It is often difficult to diagnose a depressive disorder within the geriatric population. In addition to a primary depression, elderly individuals are susceptible to other syndromes which may present in a fashion similar to depression. These include depressive reactions associated with dementia and demoralization in the elderly. In addition, depression, especially in the elderly, may masquerade as other clinical entities. Following the discussion of the diagnostic difficulties associated with depression in the elderly, we will discuss potential treatment modalities for late-onset, first-episode depression. This will include an examination of common antidepressant treatments, such as tricyclic antidepressants and monoamine oxidase inhibitors, as well as other less frequently used and experimental treatment modalities.
The Cholinergic Model of Dementia, Alzheimer Type: Progression from the Unitary Transmitter Concept
Authors: Holttum John R. , Gershon Samuel
Published: August 2007

Efforts continue toward the goal of uncovering a dominant pathogenetic and therapeutic model for Alzheimer type dementia. This article critically reviews the evolution and current status of unitary transmitter concepts, the prototype of which is the cholinergic model proposed by Deutsch and others, from early animal studies to ongoing drug trials. We conclude that evidence is sufficient to dismiss such models as a means of directing treatment and further resources. A survey of novel approaches to Alzheimer type dementia, many of which transcend unitary thought, reveals a more promising direction for further research.
The Implication of Current Therapeutic Approaches for the Cholinergic Hypothesis of Dementia
Authors: Traub M. , Freedman S.B.
Published: August 2007

The cholinergic hypothesis of Alzheimer''s disease (AD) has formed the basis for several approaches at cholinergic replacement therapy, including the administration of anticholinesterases and muscarinic agonists. Although cholinesterase inhibitors such as physostigmine and THA have been shown to improve performance in patients with AD, benefits have been modest. It is anticipated that studies employing cholinesterase inhibitors with an improved pharmacokinetic and safety profile will provide a realistic test of this therapeutic approach. Treatment with non-selective muscarinic agonists has been limited by unacceptable side-effects, and there is a need for subtype selective agents. Currently available functionally selective muscarinic agonists demonstrate low intrinsic efficacy, but it is hoped that the development of truly selective, full agonists will offer a real clinical advantage.
Canadian Study of Health and Aging
Authors: Eastwood Robin , Nobbs Holly , Lindsay Joan , McDowell I.
Published: August 2007

The Canadian Study of Health and Aging includes 18 centres, and all provinces are represented. The objectives of the study are: to estimate the prevalence of dementias, especially Alzheimer''s disease; to study risk factors for Alzheimer''s disease; to describe patterns of caring and to measure the burden on those who care for people with dementia; and to create a data base for future research. A representative sample of 10,250 Canadians aged 65 or over are recruited, including 9,000 living at home and 1,250 in institutions. Participants are screened for cognitive impairment. Those who are considered to be cognitively impaired (and an equal number who are not) are invited to undergo a clinical examination including a battery of neuropsychological tests. Proxies for the cases and controls complete a risk factor questionnaire; caregivers complete a separate questionnaire. Results of the pilot study are discussed.
Susceptibility of Brains from Patients with Alzheimer's Disease to Oxygen-Stimulated Lipid Peroxidation and Differential Scanning Calorimetry
Authors: Götz M.E. , Freyberger A. , Hauer E. , Burger R. , Sofic E. , Gsell W. , Heckers S. , Jellinger K. , Hebenstreit G. , Frölich L. , Beckmann H. , Riederer P.
Published: August 2007

The formation of thiobarbituric-acid-reactive substances (TBARS) indicative of oxygen-induced lipid peroxidation in vitro was assayed in the frontal cortex, hippocampus, putamen, basal nucleus of Meynert and substantia nigra from controls and patients with Alzheimer''s disease. A significant increase of oxygen-stimulated formation of TBARS in vitro was found in the frontal cortex and substantia nigra of Alzheimer''s-type brains, while there was only a trend to an increase in the basal nucleus of Meynert. In addition, induction of lipid peroxidation in vitro by incubation with a Fenton reagent did not result in significant differences between control and pathological brain areas. Levels of total iron in the brains from patients with Alzheimer''s disease and controls did not differ significantly with respect to the same brain region investigated. Further analysis of frontal cortex, substantia nigra and basal nucleus of Meynert using differential scanning calorimetry revealed significantly lower thermostability of these areas in Alzheimer''s disease. Our data suggest that, within distinct brain regions, Alzheimer brains differ from normal brains with respect to their susceptibility to peroxidation in vitro and to their resistance to thermic stress. These results implicate changes in cell membrane constituents and cytoarchitecture.
Primary Progressive Dementia with Swollen Chromatolytic Neurons
Authors: Mitsuyama Yoshio , Masuda Keiko , Inoue Teruhiko , Koono Masashi , Koga Shigeki , Nakamura Jungo
Published: August 2007

We report a case of dementia in which cortical degeneration with widespread presence of swollen chromatolytic neurons was the dominant pathologic feature. The previously healthy woman began to notice psychiatric symptoms at the age of 52 years. The symptoms and neurological signs progressed inexorably over the next 4 years. By the time of her death at 56 years of age, she was hopelessly disabled and lay in a mute, rigid, immobile, and seemingly insensate condition. Ultimately, quadriplegia in flexion and profound dysfunction of the extrapyramidal system, the ''akinetic-rigid syndrome'' were noted. In this patient the relentlessly progressive course, without remissions, suggests a degenerative process. Pathological examination showed frontoparietal atrophy with nerve cell loss and the presence of swollen chromatolytic cells, but there were no Pick bodies. There was nerve cell loss and gliosis in the pigmented portion of substantia nigra. Despite some pathological similarities to Pick''s disease we suggest that the distribution of nerve cell loss and the absence of Pick bodies and white matter lesions are unique to this case. Comparison of swollen chromatolytic neurons with other cerebral degenerative disorders indicates a similarity with corticonigral degeneration. This case could be included as a type of primary degenerative dementia.
Age-Dependent Learning Performance during Development and Aging in C57BL/6 Mice
Authors: Fagioli Sandro , Ammassari-Teule Martine , Rossi-Arnaud Clelia , Castellano Claudio
Published: August 2007

This experiment examined the retention of a passive avoidance response in 1-, 2-, 10- and 18-month-old C57BL/6 mice. Retention performance was assessed after training-test intervals of 24, 48 and 72 h. Adult (2 months) animals always reached the highest performance. At each interval the decline in retention performance (i.e. the rate of forgetting) varied according to the age group. With increasing testing intervals, the retention times of young, mature and old animals tended to become similar.
Hippocampal and Parahippocampal Somatostatin 28 and Neuropeptide Y Containing Neurons in Alzheimer's Disease (Part 1 of 2)
Authors: Cervera-Pierot P. , Hirsch E.C. , Javoy-Agid F. , Ransmayr G. , Hauw J.J. , Agid Y.
Published: August 2007

The somatostatinergic innervation, and by comparison that of neuropeptide Y, was examined by immunocytochemistry, in the hippocampal formation of 6 patients with clinically and neuropathologically confirmed diagnosis of Alzheimer's disease (AD) and 4 matched controls. The quantitative assessment of the somatostatin and neuropeptide Y immunoreactive cell perikarya was conducted on regularly spaced sections covering the span of the whole hippocampus and parahippocampal cortex. The estimated total number of somatostatin or neuropeptide Y containing neurons was similar in the hippocampal formation of patients with AD and controls. By contrast, the density of the somatostatinergic fibers and terminals as estimated by the optical density of the somatostatin neuropil, significantly decreased by 30-45% in all the hippocampal subregions and the parahippocampal cortex, whereas the density of the neuropeptide Y immunoreactive neuropil significantly decreased (45%) only in the parahippocampal cortex. Numerous enlarged fibers containing somatostatin or neuropeptide Y, some of which were observed within senile plaques, were detected in the brain of patients with AD. These data suggest that in AD, somatostatin and neuropeptide Y containing cell bodies in the hippocampus and parahippocampal gyrus are anatomically preserved, in spite of an altered terminal field.
Angiotensin-Converting Enzyme in Cortical Tissue in Alzheimer's and Some Other Neurological Diseases
Authors: McGeer E.G. , Singh E.A.
Published: August 2007

Angiotensin-converting enzyme (ACE), choline acetyltransferase and acetylcholinesterase were measured in seven cortical regions from the brains of 11 neurologically normal controls, 15 cases of dementia of the Alzheimer type, 6 cases of Parkinson dementia, and 12 cases with other neurological diseases. The groups did not differ significantly in age or postmortem delay. As expected, the cholinergic enzyme activities were significantly correlated with each other and were both markedly reduced in the Alzheimer and Parkinson dementia groups. Overall, ACE activity was not correlated with either of the cholinergic enzymes, and was not significantly affected by clinical category. The activity did, however, show significant regional variation and appeared somewhat higher in females than in males. The mean cortical ACE activity showed a statistically significant increase with age.
Neurologic Motor Signs in Early and Late Onset Alzheimer's Disease
Authors: Wallin Anders , Blennow Kaj
Published: August 2007

In 68 patients (mean age 71 ± 8 years) with clinically diagnosed Alzheimer's disease (AD), the presence of various neurologic motor signs was investigated, both in the total patient sample and in subgroups with early-onset AD (onset before 65 years of age; n = 30) and late-onset AD (onset at the age of 65 years or later; n = 38). Each type of basic neurologic motor sign in the total patient sample was related to basic clinical variables, brain regional symptomatology, and white-matter lesions and atrophy visualized by computerized tomography. Bipyramidal, extrapyramidal, and pseudobulbar signs were present in 21, 22 and 7%, respectively, of the total patient sample. Extrapyramidal, but not bipyramidal, signs were significantly related to the degree of dementia (p < 0.05), while pseudobulbar signs were significantly related to the presence of white-matter lesions on computerized tomography (p < 0.001). Bipyramidal signs were significantly more frequent in early-onset (37%) than in late-onset (8%) AD (p < 0.01), while extrapyramidal signs appeared in 17% of early-onset compared with 26% of late-onset AD patients. The difference in the frequency of bipyramidal signs is in line with previous findings of biological differences between early- and late-onset AD patients. Extrapyramidal signs, however, are more likely to be end-point manifestations of a disease process than indicators of an early-late-onset dichotomy. Pseudobulbar signs in AD may be indicators of white-matter lesions.
Alzheimer's Disease: Is There Evidence of Phenomenological Subtypes?
Authors: Kurz Alexander , Haupt Martin , Pollmann Stefan , Romero Barbara
Published: August 2007

A sample of 90 patients with mild or moderate dementia in Alzheimer's disease was examined for subtypes within the cognitive phenomenology and course of the disorder. Language, memory, praxia, and perception were selected as symptom areas of interest. The distributions of these symptoms and of their relationships as measured cross-sectionally at baseline did not suggest the existence of qualitatively distinct groups. The progression of cognitive impairment during the first 12 months of longitudinal observation provided no evidence of quantitative subtypes. The study confirms the marked interindividual variation in the cognitive phenomenology and course of Alzheimer's disease. It demonstrates, however, the continuous nature of this variation and its unrelatedness to age at onset or familial aggregation.
Stability of Cognitive Symptoms in Dementia of the Alzheimer Type
Authors: Pollmann Stefan , Haupt Martin , Romero Barbara , Kurz Alexander
Published: August 2007

In a longitudinal study of 90 out-patients with a clinical diagnosis of Alzheimer's disease (ICD 10) we found 11 patients with isolated cognitive symptoms that remained stable from baseline to 1-year follow-up. Two patients showed superior performance on repeated-presentation relative to single-presentation memory tests, while 4 more patients displayed superior verbal versus spatial memory or vice versa. Five other patients had outstanding scores on single psychological tests. Patients with isolated cognitive symptoms did not differ from those with generalized deficits for age, age at dementia onset, sex ratio, overall dementia severity or symptom progression.
Sundowning and Rate of Decline in Mental Function in Alzheimer's Disease
Authors: Bliwise Donald L. , Yesavage Jerome A. , Tinklenberg Jared R.
Published: August 2007

Nocturnal exacerbation of disruptive behaviors has long been recognized as a common occurrence in Alzheimer's disease (AD), however the basis for such sleep disruption is poorly understood. In this study, caregivers of 60 patients with probable/possible AD were asked to indicate the typical temporal pattern of occurrence of any of seven disruptive behaviors over the 24-hour day. Patterns of disruptive behavior were defined as sundowning (afternoon, evening, or nocturnal exacerbation), morning exacerbation, and as a nontemporally specific pattern of behavioral disruption. About 28 % of the patients were reported to sundown whereas 20% showed a pattern of morning exacerbation. Sundowning was unrelated to total score on the Mini-Mental State Exam (MMSE), however, sundowning was related to a faster rate of decline over time in selected mental functions on the MMSE. Specifically, declines in ideo-kinetic praxis abilities were related to sundowning.
Long-Term Influences on Demented Patients in Different Caring Milieus, a Collective Living Unit and a Nursing Home: A Descriptive Study
Authors: Kihlgren Mona , Bråne Görel , Karlsson Ingvar , Kuremyr Dan , Leissner Pehr , Norberg Astrid
Published: August 2007

Environmental influences on demented patients in a collective living (CL group, n = 5) and a nursing home (NH group, n = 5) were studied during 22 months. Intellectual functions rated by the GBS scale indicated a smaller deterioration in the CL group (p < 0.05). A quotient was constructed of EEG alpha/delta activities, which ratio had increased in the CL group, indicating a reduction of dementia-induced changes, and was reduced in the NH group (p < 0.05). The CL group showed signs of better social abilities, more alertness, reduced signs of depression, but caused more 'disturbances'. It seemed, however, as if these patients' behaviour were better accepted by the staff.
Sleep Quality in Geriatric Depressed Patients: Comparison with Elderly Demented Patients and Normal Controls and the Effects of Moclobemide
Authors: Lavie P. , Aharon-Peretz J. , Klein F. , Gruner F. , Epstein R. , Tzischinsky O. , Herer P.
Published: August 2007

The present study evaluated the effects of treatment with 400 mg Moclobemide in comparison with placebo on sleep quality and morning activity Ievels of geriatric depressed patients. In addition, sleep quality of these patients was compared to that of three groups of elderly patients, multi-infarct dementia, Alzheimer type dementia and normal elderly controls. Sleep quality, assessed by continuous actigraphic monitoring, was not affected by moclobemide. Morning Ievels of activity, however, were found to be significantly increased only in the moclobemide group. Comparing the measures of sleep quality derived from the actigraphic recordings between the four groups of elderly people revealed that patients with multi-infarct dementia had significantly Iower sleep quality measures than the other three groups. There were no statistically significant differences for any of the sleep quality measures between the geriatric depressed patients and the normal controls.
No-Reflow Phenomenon After Acute Myocardial Infarction Is Associated With Reduced Clot Permeability and Susceptibility to Lysis
Authors: Zalewski Jaroslaw , Undas Anetta , Godlewski Jacek , Stepien Ewa , Zmudka Krzysztof
Published: August 2007

Objective—

We assessed the relationship between fibrin clot properties and the no-reflow phenomenon after primary coronary intervention (PCI).

Methods and Results—

Epicardial blood flow was assessed by TIMI scale and corrected TIMI frame count (cTFC), and perfusion by TIMI Myocardial Perfusion Grade (TMPG) after PCI during ST-segment elevation myocardial infarction (STEMI). Fibrin clot permeability (K
s
) and susceptibility to lysis in assays using exogenous thrombin (t
50%
) and without thrombin (t
TF
) were determined in 30 no-reflow patients (TIMI ≤2) and in 31 controls (TIMI-3) after uneventful 6 to 14 months from PCI. Patients with TIMI ≤2 had lower K
s
by 18% (
P
<0.0001) and prolonged fibrinolysis by 33% for t
50%
(
P
<0.0001) and by 45% for t
TF
(
P
<0.0001). cTFC was correlated with K
s
(
r
=−0.56,
P
<0.0001), t
50%
(
r
=0.49,
P
<0.001), and t
TF
(
r
=0.54,
P
<0.001). K
s
increased in a stepwise fashion with TIMI flow (
P
<0.0001) and TMPG (
P
<0.0001), whereas both fibrinolysis times decreased with TIMI flow (
P
<0.0001 for both) and TMPG (
P
<0.01 for both). Multiple regression models showed that only K
s
and fibrinogen were independent predictors of cTFC (
P
<0.05 for both), TIMI ≤2 flow (
P
<0.05 for both) and TMPG-0/1 (
P
<0.05 for both).

Conclusions—

Survivors of myocardial infarction with a history of the no-reflow after PCI are characterized with more compact fibrin network and its resistance to lysis.
Cytokine Activation of Nuclear Factor κB in Vascular Smooth Muscle Cells Requires Signaling Endosomes Containing Nox1 and ClC-3
Authors: Miller Francis J. , Filali Mohammed , Huss Gina J. , Stanic Bojana , Chamseddine Ali , Barna Thomas J. , Lamb Fred S.
Published: August 2007

Reactive oxygen species (ROS) are mediators of intracellular signals for a myriad of normal and pathologic cellular events, including differentiation, hypertrophy, proliferation, and apoptosis. NADPH oxidases are important sources of ROS that are present in diverse tissues throughout the body and activate many redox-sensitive signal transduction and gene expression pathways. To avoid toxicity and provide specificity of signaling, ROS production and metabolism necessitate tight regulation that likely includes subcellular compartmentalization. However, the constituent elements of NADPH oxidase-dependent cell signaling are not known. To address this issue, we examined cytokine generation of ROS and subsequent activation of the transcription factor nuclear factor κB in vascular smooth muscle cells (SMCs). Tumor necrosis factor-α and interleukin (IL)-1β stimulation of SMCs resulted in diphenylene iodonium-sensitive ROS production within intracellular vesicles. Nox1 and p22
phox
, integral membrane subunits of NADPH oxidase, coimmunoprecipitated with early endosomal markers in SMCs. ClC-3, an anion transporter that is primarily found in intracellular vesicles, also colocalized with Nox1 in early endosomes and was necessary for tumor necrosis factor-α and interleukin-1β generation of ROS. Cytokine activation of nuclear factor κB in SMCs required both Nox1 and ClC-3. We conclude that in response to tumor necrosis factor-α and interleukin-1β, NADPH oxidase generates ROS within early endosomes and that Nox1 cannot produce sufficient ROS for cell signaling in the absence of ClC-3. These data best support a model whereby ClC-3 is required for charge neutralization of the electron flow generated by Nox1 across the membrane of signaling endosomes.
Upregulation of Soluble Vascular Endothelial Growth Factor Receptor 1 Contributes to Angiogenesis Defects in the Placenta of α
2B
-Adrenoceptor–Deficient Mice
Authors: Muthig Verena , Gilsbach Ralf , Haubold Miriam , Philipp Melanie , Ivacevic Tomi , Gessler Manfred , Hein Lutz
Published: August 2007

α
2
-adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 α
2
-adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the α
2
-adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in α
2
-adrenoceptor genes. Congenic α
2B
-adrenoceptor–deficient mice (
Adra2b
−/−
) developed a defect in fetal and maternal vessel formation in the placenta labyrinth at embryonic day 10.5. This defect was accompanied by reduced endothelial cell proliferation and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels in
Adra2b
−/−
as compared with
Adra2b
+/+
placentae. Microarray analysis of wild-type and mutant placentae (maternal genotype
Adra2b
+/−
) revealed 179 genes, which were significantly up- or downregulated >1.5-fold in α
2B
-deficient placentae. The type 1 receptor for vascular endothelial growth factor (Flt1), which is coexpressed with α
2B
-adrenoceptors in spongiotrophoblast and giant cells of the placenta, was found to be 2.3-fold upregulated in α
2B
-deficient placentae. Neutralization of Flt1 and its soluble splice variant sFlt1 by a specific antibody in vivo prevented the vascular defect in α
2B
-deficient placentae at embryonic day 10.5. Thus, α
2B
-adrenoceptors are essential to suppress antiangiogenic (s)Flt1 in spongiotrophoblasts to control the coordinated formation of a vascular labyrinth of fetal and maternal blood vessels in the murine placenta during development.
Interleukin-10 Expression Mediated by an Adeno-Associated Virus Vector Prevents Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats
Authors: Ito Takayuki , Okada Takashi , Miyashita Hiroshi , Nomoto Tatsuya , Nonaka-Sarukawa Mutsuko , Uchibori Ryosuke , Maeda Yoshikazu , Urabe Masashi , Mizukami Hiroaki , Kume Akihiro , Takahashi Masafumi , Ikeda Uichi , Shimada Kazuyuki , Ozawa Keiya
Published: August 2007

Pulmonary arterial hypertension (PAH) is a fatal disease associated with inflammation and pathological remodeling of the pulmonary artery (PA). Interleukin (IL)-10 is a pleiotropic antiinflammatory cytokine with vasculoprotective properties. Here, we report the preventive effects of IL-10 on monocrotaline-induced PAH. Three-week-old Wistar rats were intramuscularly injected with an adeno-associated virus serotype 1 vector expressing IL-10, followed by monocrotaline injection at 7 weeks old. IL-10 transduction significantly improved survival rates of the PAH rats 8 weeks after monocrotaline administration compared with control gene transduction (75% versus 0%,
P
<0.01). IL-10 also significantly reduced mean PA pressure (22.8±1.5 versus 29.7±2.8 mm Hg,
P
<0.05), a weight ratio of right ventricle to left ventricle plus septum (0.35±0.04 versus 0.42±0.05,
P
<0.05), and percent medial thickness of the PA (12.9±0.3% versus 21.4±0.4%,
P
<0.01) compared with controls. IL-10 significantly reduced macrophage infiltration and vascular cell proliferation in the remodeled PA in vivo. It also significantly decreased the lung levels of transforming growth factor-β
1
and IL-6, which are indicative of PA remodeling. In addition, IL-10 increased the lung level of heme oxygenase-1, which strongly prevents PA remodeling. In vitro analysis revealed that IL-10 significantly inhibited excessive proliferation of cultured human PA smooth muscle cells treated with transforming growth factor-β
1
or the heme oxygenase inhibitor tin protoporphyrin IX. Thus, IL-10 prevented the development of monocrotaline-induced PAH, and these results provide new insights into the molecular mechanisms of human PAH.
Cerebral Gas Embolism Caused by Pleural Fibrinolytic Treatment
Authors: Menéndez-González Manuel , Oliva-Nacarino Pedro , Álvarez-Cofiño Almudena
Published: August 2007

Background and Purpose—

Intrapleural fibrinolytic therapy is a technique used to treat empyemas and parapneumonic effusions. Cerebral air embolism is an unusual potentially severe complication of this technique.

Summary of Case—

A patient with parapneumonic pleural effusion underwent pleural lavage with streptokinase when he suddenly demonstrated focal neurological signs and seizures. The CT revealed multiple air-isodense spots in right hemisphere of the brain, suggesting cerebral air embolism. As a result of early diagnosis and emergency hyperbaric oxygenation, the patient recovered without delayed sequelae.

Conclusions—

Air embolism is a potentially severe complication which can occur during fibrinolytic pleural lavage, and clinicians should be aware of this risk. In this context, the onset of acute focal neurological signs or seizures should suggest the possibility of air embolism and lead to the transfer of the patient close to a hyperbaric facility within a few hours.
The Role of Immunity and Inflammation in the Progression of Atherosclerosis in Patients With HIV Infection
Authors: Coll Blai , Parra Sandra , Alonso-Villaverde Carlos , Aragonés Gerard , Montero Manuel , Camps Jordi , Joven Jorge , Masana Lluis
Published: August 2007

Background and Purpose—

The initial steps of atherosclerosis and the entry of HIV into the cell share similar biological mechanisms. Therefore, our hypothesis is that the progression of atherosclerosis in patients with HIV infection can be influenced by variations in genes implicated in both processes.

Methods and Results—

The progression of atherosclerosis over a 2-year follow-up period was measured as the combined carotid and femoral intima media thickness (IMT) in 141 patients with HIV infection. The ΔIMT (IMT
follow-up
−IMT
baseline
) values were used to segregate patients as minimal progressors or regressors (lowest ΔIMT tertile), slow progressors (mid ΔIMT tertile), and rapid progressors (highest ΔIMT tertile). Mutations CCR-5Δ32, CCR-2 64I, MCP-1-2518G, SDF1-3′A, and CX3CR-1 (T280 mol/L and V249I) in the host DNA were determined. Mean age of the patients was 38.96 (SEM: 0.61) and 68.8% were male. The mean ΔIMT was 0.045 mm (0.01) per year, which represented a significant progression (
P
<0.001) with respect to baseline values. Patients with minimal progression or regression had a significantly (
P
=0.01) higher CD4 cell count than slow progressors and rapid progressors. Multivariate analyses indicated that age and total cholesterol were positively associated with IMT progression. In contrast, the CD4 cell count, the SDF1-3′A, and the CX3CR-1 249 I mutated alleles were associated with lesser IMT progression.

Conclusion—

The course of atherosclerosis in patients with HIV infection is influenced by polymorphisms in the SDF1 and CX3CR1 genes by metabolic variables and by the CD4 cell count. These data would be of help in assessing therapeutic needs of these patients.
Matrix Metalloproteinase-9 Inhibition Attenuates Vascular Endothelial Growth Factor-Induced Intracerebral Hemorrhage
Authors: Lee Chanhung Z. , Xue Zheng , Zhu Yiqian , Yang Guo-Yuan , Young William L.
Published: August 2007

Background and Purpose—

Human brain arteriovenous malformation tissue displays increased levels of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9, a tissue protease associated with various intracerebral hemorrhage (ICH). We hypothesized that increased MMP-9 was associated with ICH induced by vascular endothelial growth factor hyperstimulation and that this effect could be attenuated by nonspecific MMP inhibition.

Methods—

We used a mouse model with adenoviral vector-mediated vascular endothelial growth factor transduction in the brain. The association of MMP-9 expression and the brain tissue hemoglobin levels, an index of ICH, after stereotactic injection of adenoviral vector-mediated vascular endothelial growth factor into caudate putamen was assessed. A dose–response study with adenoviral vector-mediated vascular endothelial growth factor and a time course study at both 24 and 48 hours postinjection were performed. Effects of minocycline, a nonspecific MMP inhibitor, and pyrrolidine dithiocarbamate, an upstream regulator of MMPs, on MMP-9 activity and thereby the degree of ICH were also tested.

Results—

Adenoviral vector-mediated vascular endothelial growth factor at the higher dose and at 48 hours induced MMP-9 levels 6-fold (n=6,
P
=0.02) and increased brain tissue hemoglobin (43.4±11.5 versus 30.3±4.1 μg/mg, n=6,
P
=0.003) compared with the adenoviral vector control. Immnunostaining was positive for MMP-9 around the cerebral vessels and the hemorrhagic areas. Minocycline and pyrrolidine dithiocarbamate administration suppressed vascular endothelial growth factor-induced MMP-9 activity (n=6,
P
=0.003 and
P
=0.01, respectively) and the associated increases in hemoglobin levels (n=5–6,
P
=0.001 and
P
=0.02, respectively).

Conclusions—

Vascular endothelial growth factor-induced ICH is associated with increased MMP-9 expression. Suppression of MMP-9 by minocycline or pyrrolidine dithiocarbamate attenuated ICH, suggesting the therapeutic potential of MMP inhibitors in cerebral vascular rupture.
Is the ‘Stroke Belt’ Worn From Childhood?
Authors: Glymour M. Maria , Avendaño Mauricio , Berkman Lisa F.
Published: August 2007

Background and Purpose—

Most Stroke Belt studies define exposure based on residence at stroke onset. We assessed whether residence in the Stroke Belt during childhood confers extra stroke risk in adulthood, even among people who left the region.

Methods—

Stroke-free Health and Retirement Study participants (n=18 070) followed up (average, 8.4 years) for first stroke (1452 events) were classified as living in 1 of 7 Stroke Belt states in childhood or at study enrollment (average age, 63 years). We used Cox proportional-hazards models to compare stroke risk for people who had never lived in the Stroke Belt with those who had lived there at both ages, in childhood only, or in adulthood only.

Results—

Compared with never having lived in the Stroke Belt, the hazard ratio for Stroke Belt residence in both childhood and adulthood was 1.23 (95% CI, 1.06, 1.43) and for Stroke Belt residence in childhood only was 1.25 (95% CI, 1.02, 1.55). Stroke Belt residence at enrollment but not during childhood was not significantly related to stroke risk (hazard ratio=1.01; 95% CI, 0.70, 1.46), but the small sample in this group resulted in wide CIs. Results changed little after risk factor adjustment, including comprehensive adult socioeconomic measures. Subgroup analyses found similar patterns by sex and birth cohort. In contrast, blacks who had lived in the Stroke Belt in childhood only did not appear to have significantly elevated stroke risk compared with blacks who had never lived in the Stroke Belt.

Conclusions—

The excess stroke risk for people who had lived in Stroke Belt states during childhood implicates early life exposures in the etiology of the Stroke Belt.
Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke
Authors: Kunte Hagen , Schmidt Sein , Eliasziw Michael , del Zoppo Gregory J. , Simard J. Marc , Masuhr Florian , Weih Markus , Dirnagl Ulrich
Published: August 2007

Background and Purpose—

The sulfonylurea receptor 1-regulated NC
Ca-ATP
channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume. We hypothesized that patients with type 2 diabetes mellitus taking sulfonylurea agents both at the time of stroke and during hospitalization would have superior outcomes.

Methods—

We reviewed medical records of patients with diabetes mellitus hospitalized within 24 hours of onset of acute ischemic stroke in the Neurology Clinic, Charité Hospital, Berlin, Germany, during 1994 to 2000. After exclusions, the cohort comprised 33 patients taking a sulfonylurea at admission through discharge (treatment group) and 28 patients not on a sulfonylurea (control group). The primary outcome was a decrease in National Institutes of Health Stroke Scale of 4 points or more from admission to discharge or a discharge National Institutes of Health Stroke Scale score of 0. The secondary outcome was a discharge modified Rankin Scale score ≤2.

Results—

No significant differences, other than stroke subtype, were observed among baseline variables between control and treatment groups. The primary outcome was reached by 36.4% of patients in the treatment group and 7.1% in the control group (
P
=0.007). The secondary outcome was reached by 81.8% versus 57.1% (
P
=0.035). Subgroup analyses showed that improvements occurred only in patients with nonlacunar strokes and were independent of gender, previous transient ischemic attack, and blood glucose levels.

Conclusion—

Sulfonylureas may be beneficial for patients with diabetes mellitus with acute ischemic stroke. Further investigation of similar cohorts and a prospective randomized trial are recommended to confirm the present observations.