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Biomedical subjects

P Werner

Publications and source records attributed to P Werner.

At least 19 recordsLinked to original sources

Correlates of family caregivers' knowledge about Alzheimer's disease.

OBJECTIVE: The aim of the present study was to assess family caregivers' level of knowledge about Alzheimer's disease and its correlates. DESIGN, SETTING AND PARTICIPANTS: Two hundred and twenty informal caregivers of an elderly person suffering from Alzheimer's disease were recruited from four large memory clinics across the country and interviewed by trained research assistants. MEASURES: Knowledge of the disease was assessed using a questionnaire including 17 items examining general knowledge, symptoms, treatment and services. Independent variables included caregivers' socio-demographic characteristics, patients' clinical characteristics and characteristics of the caregiving situation. RESULTS: Overall, low levels of knowledge were found, especially in items related to the prevalence, causes and symptoms of the disease. Low education and being a spouse were the most important vulnerability factors associated with poor knowledge. CONCLUSIONS: Further research on the correlates of caregivers' knowledge about AD should be promoted in order to allow better decision-making processes and better matching of the needs of caregivers and intervention programs.

Aged↗

Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of Alzheimer's disease, although the underlying mechanisms are unknown. Glutamate excitotoxicity has been implicated in Alzheimer's disease, Parkinson's disease, and others. We examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons from mesencephalon, the area primarily affected in Parkinson's disease. We evaluated whether these drugs protect dopaminergic neurons against excitotoxicity. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity. One hundred micro-moles ibuprofen protected both dopaminergic neurons and neurons overall against glutamate toxicity. In addition, ibuprofen alone increased the relative number of dopaminergic neurons by 47%. Thus, NSAIDs protected neurons against glutamate excitotoxicity in vitro, and deserve further consideration as neuroprotective agents in Parkinson's disease.

Acetaminophen↗

AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal fluid.

The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral load in CSF has been associated with cognitive impairment. The authors investigated if a similar association exists in patients with myelopathy. The authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no correlation between levels of HIV-1 RNA and the presence or severity of myelopathy.

Acquired Immunodeficiency Syndrome↗

S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial.

We report a pilot study of S-adenosyl-methionine (SAM) in 13 depressed patients with Parkinson's disease. All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects. SAM was administered in doses of 800 to 3600 mg per day for a period of 10 weeks. Eleven patients completed the study, and 10 had at least a 50% improvement on the 17-point Hamilton Depression Scale (HDS). One patient did not improve. Two patients prematurely terminated participation in the study because of increased anxiety. One patient experienced mild nausea, and another two patients developed mild diarrhea, which resolved spontaneously. The mean HDS score before treatment was 27.09 +/- 6.04 (mean +/- standard deviation) and was 9.55 +/- 7.29 after SAM treatment (p < 0.0001). Although uncontrolled and preliminary, this study suggests that SAM is well tolerated and may be a safe and effective alternative to the antidepressant agents currently used in patients with Parkinson's disease.

Aged↗

An integrated linkage-radiation hybrid map of the canine genome.

Purebred dogs are a unique resource for dissecting the molecular basis of simple and complex genetic diseases and traits. As a result of strong selection for physical and behavioral characteristics among the 300 established breeds, modern dogs are characterized by high levels of interbreed variation, complemented by significant intrabreed homogeneity. A high-resolution map of the canine genome is necessary to exploit the mapping power of this unusual resource. We describe here the integration of an expanded canine radiation hybrid map, comprised of 600 markers, with the latest linkage map of 341 markers, to generate a map of 724 markers-the densest map of the canine genome described to date. Through the inclusion of 217 markers on both the linkage and RH maps, the 77 RH groups are reduced to 44 syntenic groups, thus providing comprehensive coverage of most of the canine genome.

Animals↗

Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture.

Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture. However, their mechanisms of action may vary, as demonstrated by (1) differences in the morphological changes produced by these compounds; (2) varied responses to these drugs with respect to toxicity kinetics; and (3) respective rates of cell proliferation, DNA synthesis, and mitotic index. We studied the effects of acetaminophen on relative cell number further. Evidence is presented that acetaminophen induced cell death by an apoptotic mechanism after a brief burst of mitosis in which cell numbers increased transiently, followed by a reduction in cell number and an increase in DNA fragmentation, as evidenced by terminal deoxytransferase-mediated dUTP-biotin nick end labeling (TUNEL) analysis. Using cultures of adult human brain and embryonic rat brain, we demonstrated that glioma cells were several-fold more sensitive to acetaminophen than normal brain cells in culture. Finally, subtoxic doses of acetaminophen increased the sensitivity of the human glioma cells in culture to ionizing radiation. Taken together, these results suggest that acetaminophen may prove to be a useful therapeutic agent in the treatment of human brain tumors.

Acetaminophen↗

Glutamate excitotoxicity in a model of multiple sclerosis.

Glutamate excitotoxicity mediated by the AMPA/kainate type of glutamate receptors damages not only neurons but also the myelin-producing cell of the central nervous system, the oligodendrocyte. In multiple sclerosis, myelin, oligodendrocytes and some axons are lost as a result of an inflammatory attack on the central nervous system. Because glutamate is released in large quantities by activated immune cells, we expected that during inflammation in MS, glutamate excitotoxicity might contribute to the lesion. We addressed this by using the AMPA/kainate antagonist NBQX to treat mice sensitized for experimental autoimmune encephalomyelitis, a demyelinating model that mimics many of the clinical and pathologic features of multiple sclerosis. Treatment resulted in substantial amelioration of disease, increased oligodendrocyte survival and reduced dephosphorylation of neurofilament H, an indicator of axonal damage. Despite the clinical differences, treatment with NBQX had no effect on lesion size and did not reduce the degree of central nervous system inflammation. In addition, NBQX did not alter the proliferative activity of antigen-primed T cells in vitro, further indicating a lack of effect on the immune system. Thus, glutamate excitotoxicity seems to be an important mechanism in autoimmune demyelination, and its prevention with AMPA/kainate antagonists may prove to be an effective therapy for multiple sclerosis.

Animals↗

Relationships between psychotropic drug dosage, plasma drug concentration, and prolactin levels in nursing home residents.

This study aimed to characterize the relationships between administered dosages of psychotropic drugs, plasma drug concentration, and prolactin levels in a group of elderly nursing home residents. In a randomized, placebo-controlled, double-blind crossover design study, blood samples were drawn from 47 nursing home residents at least 6 hours after taking either haloperidol, thioridazine, or lorazepam. Correlations between drug dosage and plasma drug levels were significant for haloperidol and thioridazine, but not for lorazepam. Plasma drug levels were below the levels of detection for most of those taking haloperidol. Lorazepam was detected in the blood of 4 of the participants even after 3 weeks of downward titration to placebo and 6 weeks of placebo. Prolactin level was related to administered dosage only in those who were taking haloperidol. For those taking haloperidol or thioridazine, prolactin levels decreased when participants were on placebo. When an older person is taken off lorazepam, the possibility of residual drug in their bodies even 6 weeks after termination of drug use should be considered. Haloperidol may be clinically active in the brain despite no currently detectable plasma drug concentration.

Aged↗

Management of osteoporosis: a survey of Israeli physicians' knowledge and attitudes.

BACKGROUND: Osteoporosis is the most common human bone disease. It affects millions of persons throughout the world and its prevalence will increase as the population ages worldwide. OBJECTIVE: To assess Israeli physicians' attitudes and knowledge with regard to management of osteoporosis. METHODS: A questionnaire was mailed to 1,900 Israeli physicians concerning their attitudes to the management of osteoporosis, their prescribing habits, and their knowledge on the pharmacological treatment of the disease. RESULTS: Replies were received from 19% of the physicians. The respondents encouraged physical activity and cessation of smoking for all women, and prescribed estrogen replacement as the main treatment for 50-year-old women. A relatively low level of knowledge was found regarding the adequate dosage of several of the pharmacological treatments. CONCLUSIONS: The findings of the present study stress the need to provide clear guidelines and to extend physicians' knowledge regarding the management of osteoporosis.

Adult↗

'Yes' ifs, ands or buts: examining performance and correlates of the repetition task in the mini-mental state examination.

The aim of this study was to examine whether the type of sentence used in the repetition task included in the Mini-Mental State Examination (MMSE) affected performance in a group of 79 demented and 19 non-demented Hebrew-speaking elderly persons. The cognitive functioning of the participants was assessed using the MMSE and CAMCOG examinations. The performance of the repetition task was evaluated by using three sentences: the literal translation of the English language expression used in the original MMSE; a well-known Hebrew proverb consisting of monosyllabic words and rhythmic effects; and another well-known Hebrew proverb without such attributes. Only a third of the participants successfully repeated the literally translated expression. It showed low predictive value and was highly affected by education. The well-known Hebrew monosyllabic proverb showed moderate predictive value but no discriminatory ability. The other well-known Hebrew proverb performed the best. The translation of the repetition task in the MMSE to other languages is problematic. Strict adherence to the original language proved to be the least desirable choice.

Aged↗

Longitudinal predictors of non-aggressive agitated behaviors in the elderly.

Longitudinal predictors of physically and verbally non-aggressive inappropriate behaviors were examined in 200 community-dwelling elderly persons attending senior day care centers. Models based on ratings obtained from staff members and family caregivers were compared. Multiple factors contributed simultaneously to the prediction of non-aggressive behaviors. Similar to previous cross-sectional results, physically non-aggressive behaviors were predicted mainly by good health and cognitive impairment. In addition, depression emerged consistently as a predictor of physically non-aggressive behaviors in all models. Verbally non-aggressive behaviors were predicted by depressed affect and pain, confirming previous suggestions that these behaviors are related to discomfort. The relationship of these behaviors with cognitive functioning was relatively weak. Understanding the etiologies of non-aggressive problem behaviors can aid in developing appropriate care for this population.

Aged↗

Examining the reliability and validity of the Hebrew version of the Mini Mental State Examination.

The Mini Mental State Examination is used worldwide for the screening and diagnosis of dementia. The aim of the present study was to examine the reliability and validity of the Hebrew version of the Mini Mental State Examination. The Hebrew version of the Mini Mental State Examination was administered to 36 demented and 19 non-demented elderly persons. Test-retest reliability scores were calculated as exact agreement rates, and ranged from good to excellent for all the items. Strong convergent validity, as measured by the correlation between the MMSE and the CAM-COG (r = 0.94), was found. Good predictive value was observed as over three-quarters of the participants were correctly classified as demented or non-demented. The Hebrew version of the MMSE was found to be a useful and valid instrument for the determination of dementia in the elderly population.

Aged↗

Anchoring of canine linkage groups with chromosome-specific markers.

A high-resolution genetic map with polymorphic markers spaced frequently throughout the genome is a key resource for identifying genes that control specific traits or diseases. The lack of rigorous selection against genetic disorders has resulted in many breeds of dog suffering from a very high frequency of genetic diseases, which tend to be breed-specific and usually inherited as autosomal recessive or apparently complex genetic traits. Many of these closely resemble human genetic disorders in their clinical and pathologic features and are likely to be caused by mutations in homologous genes. To identify loci important in canine disease genes, as well as traits associated with morphological and behavioral variation, we are developing a genetic map of the canine genome. Here we report on an updated version of the canine linkage map, which includes 341 mapped markers distributed over the X and 37 autosomal linkage groups. The average distance between markers on the map is 9.0 cM, and the linkage groups provide estimated coverage of over 95% of the genome. Fourteen linkage groups contain either gene-associated or anonymous markers localized to cosmids that have been assigned to specific canine chromosomes by FISH. These 14 linkage groups contain 150 microsatellite markers and allow us to assign 40% of the linkage groups to specific canine chromosomes. This new version of the map is of sufficient density and characterization to initiate mapping of traits of interest.

Animals↗

Characteristics of the Functional Independence Measure in traumatic spinal cord injury.

OBJECTIVES: The characteristics of the Functional Independence Measure (FIM) were examined for spinal cord injury (SCI) in regard to norms over time by level and completeness of injury, differential benefit of motor and cognition subscales, and "ceiling effect" after rehabilitation discharge. DESIGN: Descriptive study of raw FIM data collected prospectively at admission and discharge from acute inpatient rehabilitation, and at 1, 2, and 5 years after injury. SETTING: National Database of the 18 Spinal Cord Injury Model Systems. SUBJECTS: Persons with SCI, age 16 and over, with functionally complete injuries at inpatient rehabilitation admission (ASIA grades A, B, or C), admitted to Model System an average of 8 days after injury (standard deviation = 13, median = 1 day). Maximum sample sizes for which data were available were: at rehabilitation admission, 3,971 cases; at discharge, 4,033; at year 1 postinjury, 903; 2 years, 712; and 5 years, 570. OUTCOME MEASURES: The FIM motor and cognition subscales. RESULTS: There is a substantial ceiling effect of the FIM cognition items even by inpatient rehabilitation discharge, ie, 80% to 90% of the cases average 6 to 7 (independent or modified independence) across the 5 FIM cognition items. At 1 year 89% to 97% of cases were rated independent. FIM motor items were consistent with level of injury and neurologic status. Motor items (excluding locomotion items) were highly intercorrelated (correlations range from .58 to .92 for self care, sphincter control, and mobility items). Trends over years 1, 2, and 5 were stable for both motor and cognition subscales. FIM motor gains were greatest between admission and discharge and gains continued through 1 year after injury, but at a much-decreased rate. CONCLUSIONS: The cognition items are not informative for detecting changes over time in SCI; at best, these items could serve as a crude cognition screening assessment. Motor items, in contrast, appear to reflect well the functional status of individuals. High correlations among several of the motor items suggest item redundancy. FIM motor scores illustrated the improvements in neurologic and ASIA scores in appropriate cases. Individuals with ASIA impairment grades of B or C at admission make the most gains in FIM motor scores.

Activities of Daily Living↗