Search PubMed⌕ Search

Biomedical subjects

R Spiegel

Publications and source records attributed to R Spiegel.

At least 37 records · Page 2Linked to original sources
PubMed1997

Early diagnosis of dementia via a two-step screening and diagnostic procedure.

We propose a two-step process for the assessment of dementia using standardized instruments. The family physician performs a screening consisting of taking a medical history, gathering information from relatives and friends of the patient, and administering the combined Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). Specialists examine patients with suspected dementia to confirm the diagnosis of dementia and, after a thorough differential diagnostic process, provide the family physician with recommendations for treatment. Specialists should perform neurological and psychiatric examinations, imaging (computer-assisted tomography [CT], magnetic resonance imaging [MRI]), and laboratory work-up. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) core neuropsychological battery is proposed to serve as a minimal data set that is internationally compatible. In addition, we recommend the Nurses' Observation Scale for Geriatric Patients (NOSGER) as a standard tool for functional assessment.

Aged↗
PubMed1997

Category fluency is also predominantly affected in Swiss Alzheimer's disease patients.

OBJECTIVES: To establish the comparative efficacy to differentiate between Swiss patients with dementia of the Alzheimer type (DAT) and elderly normal control subjects (NC) on two different verbal fluency tasks: category fluency and letter fluency. MATERIAL AND METHODS: Fifty Swiss German DAT patients in the early stages of the disease and 50 matched normal control subjects were compared on letter and category fluency tasks. RESULTS: DAT patients exhibited an overproportional impairment on category fluency as compared with letter fluency. Receiver operating characteristic curves (ROC) showed that category fluency correctly classified a significantly higher number of DAT patients and NC subjects (84%) than letter fluency (70%). CONCLUSION: As similar findings have been described for English-speaking DAT patients, we conclude that deficiencies in category fluency are a general phenomenon, reflecting impaired structures of semantic knowledge occurring early in the course of Alzheimer's disease.

Aged↗
PubMed1997

[Significance of impartial assessment of geriatric brain diseases].

In addition to traditional psychodiagnostic and neuropsychological methods used for assessing cognitive performance and its possible deterioration in the elderly, a number of instruments are available today that allow reliable and valid behavioural assessments to be made of geriatric patients' everyday behaviour. While rating of institutionalized geriatric patients usually focuses on the type and amount of nursing care needed, other areas of behaviour, such as activities of daily life (ADL) and instrumental ADL (IADL), memory, mood, social behaviour and disturbing behaviours are of primary interest in the case of aged individuals living in their own homes. The NOSGER (Nurses' observation scale for geriatric patients), which was introduced a few years ago, allows assessment of six important dimensions of behaviour; the scale can be easily and reliably used by professional nursing personnel as well as by untrained caregivers. The present paper describes the practical use of the instrument as well as possible graphic display of NOSGER findings; furthermore, normative values for five out of six NOSGER dimensions are given.

Activities of Daily Living↗
PubMed1997

Protocols to demonstrate slowing of Alzheimer disease progression. Position paper from the International Working Group on Harmonization of Dementia Drug Guidelines. The Disease Progression Sub-Group.

Two suggested clinical trial designs for assessing progression of Alzheimer disease are the randomized withdrawal design and the randomized start design. The most promising of these, the randomized start design, has the potential to demonstrate a delay in progression, but there remain problematic design, ethical, and statistical issues to be solved before the protocol can be used in a clinical trial. The development of biological markers of the disease process using neuroimaging or other measures also may provide a robust method of measuring disease progression and demonstrating the biological effect of a drug on the disease process.

Aged↗
PubMed1996

Genetic heterogeneity in autosomal dominant pattern dystrophy of the retina.

PURPOSE: Mutations in the retinal degeneration slow (RDS)/peripherin gene have been shown to be associated with pattern dystrophy of the retina (PDR) and other retinal dystrophies. The aim of our study was to confirm or exclude the RDS locus and the rhodopsin (RHO) locus as the disease causing locus in a large Swiss family affected with pattern dystrophy of the retina. MATERIALS AND METHODS: A Swiss family with 14 members across 3 generations affected with PDR was examined. Eleven living family members were investigated using 6 markers surrounding the RDS and RHO loci. RESULTS: Linkage to two possible candidate genes, the RDS gene on chromosome 6p and the rhodopsin gene on chromosome 3q, could be excluded. CONCLUSIONS: The family provides evidence for genetic heterogeneity of PDR and is in agreement with heterogeneity in other retinal dystrophies. Further investigations are in progress to map the gene causing PDR in this family.

Adult↗
PubMed1996

[Molecular genetic diagnosis and deletion analysis in Type I-III spinal muscular atrophy].

Autosomal recessive spinal muscular atrophy (SMA) is, after cystic fibrosis, the second most common fatal monogenic disorder. The disease is characterized by degeneration of anterior horn cells leading to progressive paralysis with muscular atrophy. Depending on the clinical type (Werdnig-Hoffmann = type I, intermediate form = type II, Kugelberg-Welander = type III), SMA causes early death or increasing disability in childhood. The SMA-critical region on the long arm of chromosome 5q13.1 contains many duplicated genes and polymorphisms. Recently, two presumptive SMA genes (survival motoneuron gene = SMN, and neuronal apoptosis inhibitory protein = NAIP) have been identified. Deletions involving critical regions of these genes are very often associated with SMA, and the extent of the deletions seems to correlate in part with disease severity. We have evaluated the diagnostic and prognostic value of molecular analysis in a large number of SMA patients. 57 patients and 78 healthy relatives were molecularly screened for deletions in the SMA critical region. We demonstrated homozygous deletions removing the SMN genes in over 90% of patients, whereas nearly 45% of patients exhibited NAIP gene deletions. Large deletions involving both genes on each chromosome are generally found in patients with severe SMA (Werdnig-Hoffman cases), while mildly affected Kugelberg-Welander cases frequently show only deleted SMN genes. Molecular classification based on combined deletion sizes, however, seems not to be exact, especially for the group with chronic SMA (type II and III). Direct DNA testing of patients in whom SMA is suspected is a highly reliable, fast, and noninvasive method. The ability to detect homozygous gene deletions in a high percentage of typical SMA patients will much improve genetic counselling and prenatal diagnosis in affected families.

Adult↗
PubMed1996

Psychiatric symptoms and CAG expansion in Huntington's disease.

The mutation responsible for Huntington's disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers.

Adult↗
PubMed1996

Somatic stability of the expanded CAG trinucleotide repeat in X-linked spinal and bulbar muscular atrophy.

Expansion of trinucleotide repeats has now been associated with eight inherited diseases: X-linked spinal and bulbar muscular atrophy, two fragile X syndromes, myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type I, dentatorubral pallidoluysian atrophy and Machado-Joseph disease. It has been shown that these expanded DNA repeats are unstable in number when transmitted from parents to offspring ("meiotic instability"), while somatic variation in repeat number has also been found in the fragile X syndrome and myotonic dystrophy. Moderate meiotic instability has been demonstrated in X-linked spinal and bulbar muscular atrophy (SBMA, Kennedy's disease). In order to determine if the expanded CAG repeat in SBMA also shows somatic instability, we compared different tissues from two patients with SBMA. We then examined the in vitro stability of the CAG repeat expansion by analyzing fibroblast cell cultures. Length comparison of expanded CAG repeats from all these materials clearly demonstrates that the CAG trinucleotide repeat in SBMA does not exhibit somatic variation.

Cells, Cultured↗
PubMed1996

Cystic fibrosis associated with neuronal intestinal dysplasia type B: a case report.

The authors present the case of a newborn girl who had cystic fibrosis associated with neuronal intestinal dysplasia type B (NID-B). The association is rare but must be considered in the differential diagnosis of gastrointestinal problems in patients with cystic fibrosis. The present case elucidates the intestinal problems that can arise with this combination of diseases. Although the unusual association found in this patient could have been a random occurrence, the possibility of an NID-B determining gene localized on chromosome 7q should be considered.

Chromosomes, Human, Pair 7↗
PubMed1996

Validation of the NOSGER (Nurses' Observation Scale for Geriatric Patients): reliability and validity of a caregiver rating instrument.

The Nurses' Observation Scale for Geriatric Patients (NOSGER) is a rating scale for use in geriatric patients that can be applied by nurses or other caregivers. It deals with the daily behavior of elderly patients and measures impairment in six areas (dimensions): memory; instrumental activities of daily living (IADL); (basic) activities of daily living (ADL); mood; social behavior; and disturbing behavior. Objectivity, stability, construct validity, and acceptance of the scale have been established in previous studies using an earlier version of the NOSGER. The present validation study considered 50 healthy old subjects, 25 patients with mild dementia, 25 patients with advanced (mostly moderate according to DSM-III-R criteria) dementia, and 25 elderly patients with depression. The NOSGER was completed by relatives in the case of subjects living in their own homes and by nurses or other caregivers for institutionalized subjects. In addition to the NOSGER, selected tests of concentration, memory, and performance were applied as outside criteria. Interrater reliability (objectivity) was estimated by variance component analysis. Values between rtt = .68 and rtt = .89 (all p < .001) were found for the six NOSGER dimensions, the values being higher for the cognitive dimensions (memory, IADL, ADL) than for the noncognitive ones (mood, social behavior, disturbing behavior). Retest reliability (stability), which was calculated via rank order correlations, was somewhat higher for the cognitive NOSGER dimensions (memory rs = .91, IADL rs = .92, ADL rs = .88; p < .001) than for the noncognitive ones (mood rs = .85, social behavior rs = .87, disturbing behavior rs = .84; p < .001). All these values satisfy the level of rtt > or = .80 required in accordance with psychometric standards. The concurrent validity of the NOSGER dimensions was assessed using correlations with external criteria with which similarity of content was expected. The NOSGER dimensions memory, IADL, ADL, and social behavior were found to correlate closely with external criteria of similar content, whereas no satisfactory concurrent validities were found for the dimensions mood or disturbing behavior. The NOSGER dimensions were also correlated with a number of unrelated external criteria so as to reveal any discordances. For the dimensions memory, IADL, ADL, and social behavior, no clear-cut discriminant validities were found. This suggests that these four dimensions may function as parameters not just of different areas of behavior, but also of a general factor that might be described as "cognitive intactness." As a further aspect of construct validity, significant differences (all p < .001) between the four groups of subjects were found in five of the six NOSGER dimensions (memory, IADL, ADL, mood, social behavior): The healthy subjects differed significantly from all three patient groups in five of the six dimensions; the moderately demented group differed from the depressed group in four of the six dimensions and from the mildly demented group in two of the six dimensions; and the mildly demented group differed significantly from the depressed group in terms of mood (significance levels are after application of the Bonferroni correction). Significant group differences (p generally < .001) were also found for most of the objective performance tests used (data not presented).

Activities of Daily Living↗
PubMed1996

Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease.

We used PET scans with the tracers [18F]fluorodeoxyglucose (FDG) and [11C]raclopride (RACLO) to study glucose metabolism and dopamine D2 receptor binding in the caudate nucleus and putamen of 18 carriers of the Huntington's disease gene mutation (10 asymptomatic subjects and eight untreated symptomatic Huntington's disease patients in an early disease stage). We also performed MRI scans and measured the bicaudate ratio (BCR) in the same subjects. Data were compared with those from nine mutation-negative members of Huntington's disease families and separate groups of age matched controls. The PET scans were repeated 1.5-3 years later in six of the asymptomatic gene carriers. Symptomatic Huntington's disease patients showed a marked reduction of FDG and RACLO uptake in the caudate nucleus and putamen and a significant increase of BCR. Asymptomatic mutation carriers revealed significant hypometabolism in the caudate nucleus and putamen. The RACLO binding was significantly decreased in the putamen. Decrements of caudate nucleus tracer uptake, particularly RACLO, correlated significantly with BCR increases in both symptomatic and asymptomatic gene carriers. In asymptomatic carriers, metabolic and receptor binding decreases were also significantly associated with the CAG repeat number but not with the individual's age. Discriminant function analysis correctly classified clinical and genetic status in 24 of 27 subjects on the basis of their striatal PET values (83% sensitivity and 100% specificity). Three asymptomatic mutation carriers were classified/grouped together with mutation-negative subjects, indicating that these individuals had normal striatal RACLO and FDG uptake. Follow-up PET data from gene-positive subjects showed a significant reduction in the mean striatal RACLO binding of 6.3% per year. Striatal glucose metabolism revealed an overall non significant 2.3% decrease per year. These data indicate that asymptomatic Huntington's disease mutation carriers may show normal neuronal function for a long period of life. These findings also suggest that it may be possible to predict when an asymptomatic gene carrier will develop clinical symptoms from serial PET measurements of striatal function.

Adult↗
PubMed1995

Improving the diagnostic accuracy of the Mini-Mental State Examination.

INTRODUCTION: We determined the diagnostic accuracy of the Mini-Mental State Examination (MMSE) for dementia of the Alzheimer type (DAT) in an outpatient geriatric referral center in Switzerland. MATERIAL & METHODS: DAT patients and elderly controls were assigned to two groups: a validation sample (70 DAT patients; 50 controls) and a cross-validation sample (133 DAT patients; 43 controls). A Receiver Operating Characteristic curve was generated to derive the optimal MMSE cut-off score in the validation sample. RESULTS: The optimal MMSE cut-off was < 26/30 (sensitivity of 74%, specificity of 100%). Adjustments for age and education were necessary. The cross-validation confirmed these findings. CONCLUSION: iN A clinical setting the MMSE cut-off should be increased to < 26/30. A thorough neurobehavioral assessment is still necessary for a complete evaluation.

Age Factors↗
PubMed1995

A PCR based X-chromosome inactivation assay for carrier detection in X-linked immunodeficiencies using differential methylation of the androgen receptor gene.

Carrier detection in X-linked immunodeficiencies (X-SCID, WAS, XLA) relies on the demonstration of non-random X inactivation patterns in blood cell lineages. Only a limited number of cells are available after cell separation methods. PCR-based techniques are therefore necessary to analyze active and inactive X chromosomes. Amplifying a polymorphic CAG repeat in the first exon of the androgen receptor gene after selective digestion of the active X chromosome with a methylation-sensitive restriction enzyme allows to distinguish between the paternal and maternal alleles and to identify their methylation status. DNA from B-, T-lymphocytes and total peripheral leukocytes of normal males, females and obligate carriers of X-linked immunodeficiencies were analyzed. The results of this PCR-based X inactivation assay are concordant with the standard methylation studies at the DXS255 locus using Southern blotting. This PCR assay provides a rapid and informative (heterozygosity > 90%) method in carrier detection of X-linked immunodeficiencies and other X-linked disorders, which show non-random X inactivation in cell lineages from the affected tissues.

DNA↗