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E Mohr

Publications and source records attributed to E Mohr.

At least 37 records · Page 2Linked to original sources
PubMed2000

Rivastigmine for Alzheimer's disease: Canadian interpretation of intermediate outcome measures and cost implications.

BACKGROUND: Clinical studies have shown that patients with Alzheimer's disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. OBJECTIVE: The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. METHODS: Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimer's Disease Assessment Scale-Cognitive Function, Clinician's Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. RESULTS: The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panel's opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home care and institutionalization, positive effects on caregiver health, and less time lost from work for the caregiver. CONCLUSIONS: From the perspective of a Canadian specialist panel, rivastigmine treatment for AD produces clinically relevant effects for patients that are beneficial to caregivers. These effects suggest decreased use of caregiver resources and delays in the need for institutionalization, both of which reduce societal costs.

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PubMed2000

Acute nicotine administration in Alzheimer's disease: an exploratory EEG study.

Previous findings of cognitive deficits and EEG slowing in Alzheimer's patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.

Administration, Oral↗
PubMed2000

Electroencephalographic coherence in Alzheimer's disease: comparisons with a control group and population norms.

Previous research from independent laboratories has shown reduced electroencephalographic coherence in patients diagnosed with dementia of the Alzheimer type (DAT). This study added to this work by comparing interhemispheric and intrahemispheric coherence in nonmedicated DAT patients (n = 35) with that of a normal control group (n = 30), as well as with a data bank of population norms. Raw and Z-score transformed values showed reduced coherence, interhemispherically (in delta, theta, alpha, and beta bands) and intrahemispherically (delta and theta bands) in DAT patients with both comparison procedures. Discriminant analysis correctly classified 73% to 75% of patients. The results are discussed in relation to earlier research, "trait" versus "state" factors, the cholinergic system, and cognitive processes in dementia.

Aged↗
PubMed2000

Pharmaco-EEG test dose response predicts cholinesterase inhibitor treatment outcome in Alzheimer's disease.

Previous investigations have indicated that a single dose pharmaco-EEG may predict the outcome of 4-7 weeks of tetrahydroaminoacridine (THA) treatment in dementia of the Alzheimer type (DAT). This open trial study further examined the relationship of quantitative EEG in relation to treatment response by assessing 24 probable DAT patients at baseline, 2 h after their first oral dose (30 mg), and after 12 weeks of THA treatment. Compared to EEG norms, patients, in general, evidenced EEG slowing, as shown by excessive slow (theta) and diminished fast (alpha and beta) wave power as well as reduced mean frequencies which were present prior to treatment as well as at the end of treatment. The EEG of patients exhibiting stable or improved scores on the Mini-Mental State examination (MMSE) at 12 weeks showed a significantly faster baseline mean alpha frequency as well as a significant reduction in relative theta power following the single THA test dose compared to deteriorated patients. A discriminant analysis using test dose response EEG variables correctly classified 75-79% of these two patient groups, suggesting that this procedure may be a useful approach for optimizing patient selection for antidementia treatments.

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PubMed1999

Subcellular RNA compartmentalization.

The phenomenon of mRNA sorting to defined subcellular domains is observed in diverse organisms such as yeast and man. It is now becoming increasingly clear that specific transport of mRNAs to extrasomal locations in nerve cells of the central and peripheral nervous system may play an important role in nerve cell development and synaptic plasticity. Although the majority of mRNAs that are expressed in a given neuron are confined to the cell somata, some transcript species are specifically delivered to dendrites and/or, albeit less frequently, to the axonal domain. The physiological role and the molecular mechanisms of mRNA compartmentalization is now being investigated extensively. Even though most of the fundamental aspects await to be fully characterized, a few interesting data are emerging. In particular, there are a number of different subcellular distribution patterns of different RNA species in a given neuronal cell type and RNA compartmentalization may differ depending on the electrical activity of nerve cells. Furthermore, RNA transport is different in neurons of different developmental stages. Considerable evidence is now accumulating that mRNA sorting, at least to dendrites and the initial axonal segment, enables local synthesis of key proteins that are detrimental for synaptic function, nerve cell development and the establishment and maintenance of nerve cell polarity. The molecular determinants specifying mRNA compartmentalization to defined microdomains of nerve cells are just beginning to be unravelled. Targeting appears to be determined by sequence elements residing in the mRNA molecule to which proteins bind in a manner to direct these transcripts along cytoskeletal components to their site of function where they may be anchored to await transcriptional activation upon demand.

Animals↗
PubMed1999

Development of heart rate rhythmicity in Muscovy duck embryos.

The heart rate (HR) of Muscovy duck embryos (Cairina moschata f. domestica) was continuously recorded from as early as the 21st day of incubation (D21) until hatching (D34/35). The aim of the study was to investigate the influence of phonoperiods consisting of different acoustic stimuli on the course of HR and the development of HR periodicities during this period. Incubation was carried out at a constant temperature and in constant darkness. Until D25 HR was dominated by decelerative fluctuations only, indicating a main input from the parasympathetic system on the heart. Later sympathetic influences increased progressively. HR periodicity was investigated by means of chi 2-periodogram and fast Fourier transformation. Between D26 and D30 statistically significant and stable HR periodicities developed gradually. They had periods in the range from 5 to 38 h. Ultra-, circa- and infradian rhythms (< 20, 24 +/- 4 and > 28 h, respectively) occurred in parallel in some cases in the same embryo. The for the HR course important periods were dissimilar between individual embryos and had different intensities. There was no indication that acoustic stimulation (phonoperiods) had any effect on the development of HR periodicities.

Acoustic Stimulation↗
PubMed1999

Monitoring training success using a lactate-speed relationship.

Monitoring training by measuring blood lactate content is a well-known procedure in sports physiology. Because of the difficulties in standardizing a test procedure in field studies, this method is fraught with considerable problems when applying it to race horses. The aim of the present study was to develop a test procedure which is able to give evidence about the training state of different race horses after nonidentical test-loads. Under almost identical environmental conditions, the level of blood lactate was determined in five trotters which were kept in training. Immediately after the single phases of a three-stage test procedure (handicap: 'small', 'medium' and 'high' load for the animals chosen at the discretion of the coach) blood samples were drawn. The lactate value was set in relation to the speed of each animal. A curve of the equation y = y0 + e(k + b*x) was fitted with r2 > 0.93 to these data. With the aid of this equation, the 'comparative speed', V, was calculated; this is the arithmetic mean of the velocities V4, V8 and V20, obtained by inserting the appropriate values for (imaginary) lactic acid concentrations in the formula. With the aid of V it was possible to detect both an increase and a decrease in physical fitness. In this way, animals tested together on one date, as well as the development of one animal tested on several dates, can be scored. Advantages and limitations of the method are discussed in detail.

Animals↗
PubMed1999

EEG and the passive P300 in dementia of the Alzheimer type.

Quantitatively analyzed resting electroencephalographic (EEG) activity and P300 event-related potentials elicited with a passive tone sequence paradigm were examined in 30 patients with dementia of the Alzheimer type (DAT) and 15 age matched controls. Background electrical rhythms of DAT patients evidenced slowing as shown by increased absolute and relative amplitudes in slow frequency bands and decreased amplitudes in fast frequency bands (relative to controls). Electrical slowing was more evident in patients with higher clinical ratings of global intellectual deterioration. Passive P300 amplitude and latency did not differentiate patients and controls and were not related to severity of dementia.

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PubMed1998

FlyNets and GIF-DB, two internet databases for molecular interactions in Drosophila melanogaster.

GIF-DB and FlyNets are two WWW databases describing molecular (protein-DNA, protein-RNA and protein-protein) interactions occuring in the fly Drosophila melanogaster (http://gifts.univ-mrs.fr/GIFTS_home_page.html ). GIF-DB is a specialised database which focuses on molecular interactions involved in the process of embryonic pattern formation, whereas FlyNets is a new and more general database, the long-term goal of which is to report on any published molecular interaction occuring in the fly. The information content of both databases is distributed in specific lines arranged into an EMBL- (or GenBank-) like format. These databases achieve a high level of integration with other databases such as FlyBase, EMBL, GenBank and SWISS-PROT through numerous hyperlinks. In addition, we also describe SOS-DGDB, a new collection of annotated Drosophila gene sequences, in which binding sites for regulatory proteins are directly visible on the DNA primary sequence and hyperlinked both to GIF-DB and TRANSFAC database entries.

Animals↗
PubMed1998

Evaluation of selection criteria used in Alzheimer's disease clinical trials.

BACKGROUND: In the absence of a biological marker for Alzheimer's disease (AD), diagnosis has to be achieved using clinical criteria sets such as those outlined in DSM-IV, NINCDS-ADRDA, or ICD-10. As these criteria are quite broadly defined, there may be inter-rater variability in interpretation. METHODS: Using a previously published CT scan measuring technique which correlates well with diagnoses achieved using the NINCDS-ADRDA criteria as interpreted at our clinic, we chose to independently examine and reach a diagnosis in patients selected for participation in clinical trials of therapeutic agents for the treatment of AD. Forty-four CT scans from six investigators across Canada were examined using this model. All patients had been diagnosed as having AD by NINCDS-ADRDA criteria and were deemed acceptable to participate in a clinical trial. RESULTS: The diagnostic concordance achieved in the original published model was 91.5%. The diagnostic concordance in the population currently being studied was 77.3%. However when examined by site, results ranged from 57.1% to 100%. Using the model, an index of atrophy and a probability of diagnosis of AD can be determined. Across sites, there were statistically significant differences in these measures (p < or = 0.035). The mean probability of diagnosis of AD across sites ranged from 0.56 to 0.94. Although the sites with lower probabilities had slightly lower mean ages and slightly less atrophy, there was no overall correlation of the atrophy measures with age. CONCLUSIONS: Current results raise the possibility that the selection of patients for AD clinical trials using current diagnostic criteria sets may not be adequate and conclusions with respect to agent efficacy could be flawed.

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PubMed1998

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity.

Neuropsychological assessment of older individuals with dementing illnesses has suffered from a lack of appropriately designed test instruments. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was developed for the dual purposes of identifying and characterizing abnormal cognitive decline in the older adult and as a neuropsychological screening battery for younger patients. The entire battery takes less than 30 minutes to administer, and yields scaled scores for five cognitive domains. The current study reports preliminary clinical validity results with the RBANS, comparing very mildly demented patients with a diagnosis of probable Alzheimer's disease (n = 20) to patients with Huntington's disease (n = 20) and normal controls (n = 40). Although the patient groups had essentially identical total scores on the RBANS, they exhibited opposite profiles, differing significantly on four of the five subsections. The AD patients performed most poorly on Language, and Delayed Memory subsections, while the HD patients obtained their lowest scaled scores on the Attention and the Visuospatial/Constructional subsections. These results are consistent with the neuropsychological profiles of these dementing disorders derived from lengthier standardized tests and experimental investigations. In addition, even those patients who performed above the suggested cut-off points on the MMSE and the Dementia Rating Scale scored significantly below their controls on the RBANS. These data suggest that the RBANS is effective at both detecting and characterizing dementia of different etiologies.

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PubMed1998

Selected blood parameters during recovery from strenuous running exertion in trotters.

During training, in 10 trotters, blood samples from the vena jugularis were taken before and after a heat with 80% of maximum capability as well as in the recovery period. Lactic acid concentration and pH-value, haematocrit and haemoglobin content, as well as protein concentration and osmolality were measured. With the exception of protein concentration, the time course of the values during the recovery could be described by simple mathematical models (biexponential or exponential equations). Only in the case of blood lactate concentration, the basal value was not yet achieved 120 min after the end of exercise. In the case of the other examined parameters, the homeostasis was restored earlier. Therefore, it seems to be recommendable when performing tests with preliminary heats and finals on the same day to stick to a break of at least 2 h between two races.

Animals↗
PubMed1997

GIF-DB, a WWW database on gene interactions involved in Drosophila melanogaster development.

GIF-DB (Gene Interactions in the Fly Database) is a new WWW database (http://www-biol.univ-mrs.fr/ approximately lgpd/GIFTS_home_page. html ) describing gene molecular interactions involved in the process of embryonic pattern formation in the flyDrosophila melanogaster. The detailed information is distributed in specific lines arranged into an EMBL- (or SWISS-PROT-) like format. GIF-DB achieves a high level of integration with other databases such as FlyBase, EMBL and SWISS-PROT through numerous hyperlinks. The original concept of interaction databases examplified by GIF-DB could be extended to other biological subjects and organisms so as to study gene regulatory networks in an evolutionary perspective.

Animals↗
PubMed1997

A randomized, controlled trial of linopirdine in the treatment of Alzheimer's disease.

OBJECTIVES: We tested the efficacy and safety of linopirdine, a novel phenylindolinone, in the treatment of Alzheimer's disease. METHODS: A multicentre, randomized, double-blind, parallel group, placebo-controlled trial of linopirdine (30 mg three times per day or placebo). Patients (n = 382, 55% male, 98% Caucasian, age range 51-95 years) with mild or moderate Alzheimer's disease, of whom 375 received at least one treatment dose were analysed. There were no important differences between the groups at baseline. RESULTS: No difference was seen in Clinical Global Impression scores between patients receiving placebo and those receiving linopirdine (n = 189). Small differences in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores were seen throughout the study favouring linopirdine; at 6 months the ADAS-Cog scores were 20.2 (linopirdine) and 22.1 (placebo) p = 0.01. CONCLUSIONS: This trial did not detect clinically meaningful differences in patients receiving linopirdine for 6 months, despite evidence of a small degree of improved cognitive function. Further studies may benefit from more sensitive tests of treatment effects in Alzheimer's disease.

Aged↗
PubMed1997

Treatment of Alzheimer's disease with sabeluzole: functional and structural correlates.

Sabeluzole, a new benzothiazole derivative, has been shown to be neurobiologically active preclinically and clinically appears to exert beneficial effects on memory. In this study, sabeluzole (5 or 10 mg twice daily vs. placebo) was investigated in patients with probable Alzheimer's disease over 1 year, with assessments of cognitive performance and structural changes. Cognitive performance was measured using the Alzheimer's Disease Assessment Scale periodically during treatment. Potential structural correlates in the frontal horn, caudate, third ventricle and hippocampal regions were examined by obtaining computerized tomographic (CT) images before and after treatment. Patients receiving sabeluzole evidenced greater stability than did placebo-treated patients in some cognitive measures. CT measures showed no significant changes from baseline, but some weak associations were found between relative preservation of cognitive function and smaller structural declines in the third ventricle and hippocampus. Cognitive outcome measures suggest that sabeluzole may have potential in slowing the cognitive deterioration of Alzheimer's disease. Furthermore, the method used to explore potential benefits on a morphologic level, although negative in this study, could yet have potential.

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PubMed1997

Dendritic localization of rat vasopressin mRNA: ultrastructural analysis and mapping of targeting elements.

Transcripts encoding the vasopressin precursor are located in axons and dendrites of rat hypothalamic magnocellular neurons. While the axonal vasopressin mRNA has been extensively characterized both at the biochemical and morphological level, little is known about those transcripts residing in dendrites of magnocellular neurons. As revealed by in situ hybridization at the electron microscopic level, the mRNA is located in proximal and distal dendritic segments and is exclusively confined to regions containing rough endoplasmic reticulum. These results suggest that dendrites of hypothalamic neurons may be capable of local precursor synthesis independent of that occurring in the cell somata. A heterologous system has been employed to define cis-acting elements within the vasopressin mRNA which may be involved in dendritic compartmentalization. Expression vector constructs consisting of the cytomegalovirus promoter coupled to the rat vasopressin cDNA have been injected into the cell nuclei of cultured neurons derived from embryonic rat superior cervical ganglia. Vector-encoded vasopressin transcripts were also sorted to dendrites of these neurons indicating that the molecular determinants of dendritic mRNA transport are not cell specific. Mapping of the targeting elements revealed two segments within the vasopressin mRNA that are able to confer dendritic compartmentalization to alpha-tubulin mRNA which is normally confined to the cell body.

Animals↗
PubMed1997

SPECT in AD.

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Alzheimer Disease↗