Search PubMed⌕ Search

Biomedical subjects

D W Anderson

Publications and source records attributed to D W Anderson.

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

Quality of pharmacotherapy consultations provided by drug information centers in the United States.

We evaluated the performance of 116 U.S. drug information centers in responding to specific questions about drugs. The primary measures were correctness of responses and extent of probing for patient data. Questions addressed the effect of ranitidine on blood alcohol concentrations, the potential interaction between didanosine and dapsone, prevention of nonsteroidal antiinflammatory drug (NSAID)-induced peptic ulcers, and use of erythromycin for diabetic gastroparesis. The percentages of centers providing correct overall responses were 70% for the ranitidine question, 90% for the didanosine-dapsone question, 8% for the NSAID question, and 20% for the erythromycin question. For the three patient-specific questions, the percentages of centers eliciting vital patient data were 27% for the didanosine-dapsone question, 86% for the NSAID question, and 5% for the erythromycin question. In providing pharmacotherapy consultations, drug information centers generally failed to obtain pertinent patient data, thereby risking incorrect responses and inappropriate recommendations.

Drug Information Services↗
PubMed1999

Characterization of the human and mouse unconventional myosin XV genes responsible for hereditary deafness DFNB3 and shaker 2.

Mutations in myosin XV are responsible for congenital profound deafness DFNB3 in humans and deafness and vestibular defects in shaker 2 mice. By combining direct cDNA analyses with a comparison of 95.2 kb of genomic DNA sequence from human chromosome 17p11.2 and 88.4 kb from the homologous region on mouse chromosome 11, we have determined the genomic and mRNA structures of the human (MYO15) and mouse (Myo15) myosin XV genes. Our results indicate that full-length myosin XV transcripts contain 66 exons, are >12 kb in length, and encode 365-kDa proteins that are unique among myosins in possessing very long approximately 1200-aa N-terminal extensions preceding their conserved motor domains. The tail regions of the myosin XV proteins contain two MyTH4 domains, two regions with similarity to the membrane attachment FERM domain, and a putative SH3 domain. Northern and dot blot analyses revealed that myosin XV is expressed in the pituitary gland in both humans and mice. Myosin XV transcripts were also observed by in situ hybridization within areas corresponding to the sensory epithelia of the cochlea and vestibular systems in the developing mouse inner ear. Immunostaining of adult mouse organ of Corti revealed that myosin XV protein is concentrated within the cuticular plate and stereocilia of cochlear sensory hair cells. These results indicate a likely role for myosin XV in the formation or maintenance of the unique actin-rich structures of inner ear sensory hair cells.

Alternative Splicing↗
PubMed1999

Autopsy patterns for Parkinson's disease and related disorders in Olmsted County, Minnesota.

Using a records-linkage system, we determined the frequency and distribution of brain autopsies in residents of Olmsted County, Minnesota, in whom parkinsonism developed during 1976 through 1990. Of the 364 incident cases identified, 235 patients were deceased at the time of record abstraction. The overall autopsy rate was low (23%). Diagnostic certainty (for PD), diagnostic type (PD versus other parkinsonism), sex, age at death, and location at death were important selection factors for autopsy.

Autopsy↗
PubMed1999

Norms for the Mini-Mental State Examination in a healthy population.

BACKGROUND: Although the Mini-Mental State Examination (MMSE) is widely used in clinical practice, few norms exist for healthy populations covering a broad range of ages. OBJECTIVE: To obtain MMSE norms specific for age, gender, and education in healthy adults. METHODS: From the population registers of seven communities across Italy, we selected a proportionate random sample of residents age 20 to 79 years to evaluate their health status with respect to conditions affecting cognitive performance. This sample yielded 908 persons who were deemed to be without cognitive impairment and who were then given the MMSE. We calculated fifth percentile norms and presented them as step functions. We then validated the norms as a screening tool for dementia in persons age 65 to 79 years. The validation was based on unpublished data from a separate study and involved estimates of sensitivity and specificity. RESULTS: The norms declined with advancing age, especially for less educated women. Given any age and sex, the norms were higher for individuals with higher educational levels. In screening for dementia, the norms had a sensitivity of 85% and a specificity of 89%. CONCLUSIONS: When using MMSE scores, it is important to account for age, gender, and education, especially in populations where the educational level is low. Expressing MMSE norms as step functions provides an easy-to-use tool for neurologists and other clinicians.

Adult↗
PubMed1998

2-Chloro-4-(trifluoromethyl)pyrimidine-5-N-(3',5'- bis(trifluoromethyl)phenyl)-carboxamide: a potent inhibitor of NF-kappa B- and AP-1-mediated gene expression identified using solution-phase combinatorial chemistry.

Described is the identification of a novel series of compounds that blocks the activation of two key transcription factors, AP-1 and NF-kappa B. These transcription factors regulate the expression of several critical proinflammatory proteins and cytokines and represent attractive targets for drug discovery. Through the use of high throughput screening and solution-phase parallel synthesis, inhibitors of both NF-kappa B and AP-1 were identified. In subsequent testing, these compounds were also shown to block both IL-2 and IL-8 levels in the same cells. One of the most potent compounds in this series, 28, was active in several animal models of inflammation and immunosuppression, thus validating the importance of AP-1 and NF-kappa B as potential therapeutic targets. The synthesis and preliminary structure-activity relationships of these compounds is addressed.

Actins↗
PubMed1998

Case ascertainment uncertainties in prevalence surveys of Parkinson's disease.

Using unpublished data from five completed prevalence surveys of Parkinson's disease (PD), we investigated case ascertainment uncertainties that potentially have a direct effect on prevalence. These uncertainties arise from the choice of diagnostic criteria, the choice of screening method, and the amount of information lost because of nonresponse. The surveys were conducted in Argentina, India, China, Italy, and the Netherlands. Our analyses consisted of simple comparisons of prevalence results, positive predictive values (a screening measure), and nonresponse percentages. We found that (a) prevalence comparisons between surveys have diminished value if the surveys used different diagnostic criteria for PD; (b) screening performance may be affected adversely if symptom questions are answered by one family member for the entire family living together rather than by each family member individually; and (c) nonresponse from refusal or unavailability does not necessarily lead to bias, but special caution may be appropriate with prevalence results pertaining to elderly women.

Aged↗
PubMed1998

Pitfalls in neuroepidemiologic research.

In neuroepidemiologic research, there are many pitfalls to trap unwary investigators, whether the project is a survey, a case-control study, or some other type of study. We briefly discuss pitfalls relating to: research preliminaries (e.g., failure to decide on study objectives); personnel and training (e.g., deficient training); data collection (e.g., ineffective supervision); data ownership and data sharing (disagreement about how the data will be used), and report preparation (e.g., failure to interpret results in the context of uncertainties arising from the design and implementation of the research). Awareness of these pitfalls will reduce the likelihood of flawed or ineffective neuroepidemiologic research.

Data Collection↗
PubMed1997

Comparison of HIV-1 envelope-specific CD4+ T cell lines simultaneously established from peripheral blood mononuclear cells and lymph node biopsy in HIV-1-infected individuals.

HIV-1 envelope-specific CD4+ T cell lines were established simultaneously from PBMC and lymph node mononuclear cells of two HIV-1-infected patients. Three recombinant envelope proteins were used to establish the CD4+ T cell lines: gp160NL4-3, gp120IIIB, and gp120MN. Six T cell lines were established from the first patient, one for each Ag from each compartment, and four T cell lines, two per compartment, were established from the second patient. Each line was challenged with a panel of overlapping peptides spanning the entire gp120 sequence to define its T cell epitope specificity. The pattern of recognition for all the lines from any given patient was similar between compartments. Each patient had a different pattern of peptide recognition. TCR analysis showed a heterogeneous usage of Vbeta between lines with same peptide specificity and established from different compartments. These data suggest that the cellular immune response does not phenotypically vary between the peripheral blood and lymph node compartments, but demonstrates genotypic heterogeneity, showing possible redundancy of the immune response to HIV-1 gp160.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Prevalence of Parkinson's disease in Junín, Buenos Aires Province, Argentina.

We investigated the prevalence of Parkinson's disease (PD) in a South American city: Junín, Buenos Aires Province, Argentina. At dwellings systematically selected, the case finding involved household screenings and neurological examinations (i.e., a two-phase survey approach). Only persons 40 years of age or older were eligible (N = 7,765). There were 51 cases of PD identified, yielding a crude prevalence of 656.8 per 100,000 population. The age-specific prevalence was consistently higher in men than women, and it increased with advancing age for both sexes. In addition to prevalence figures. we present tallies related to clinical features of PD, as well as tallies related to other subtypes of parkinsonism.

Adult↗
PubMed1997

A population perspective on diagnostic criteria for Parkinson's disease.

For Parkinson's disease (PD), little is known about how the choice of diagnostic criteria affects research results. Using data on PD from three community studies (from Argentina, the Netherlands, Italy), we compared the impact on prevalence of several sets of diagnostic criteria. Each set was based on cardinal signs--resting tremor, bradykinesia, rigidity, impaired postural reflexes--and required that other parkinsonism be excluded. Some sets had additional requirements related to duration of symptoms, asymmetry of signs, or response to medication. In terms of prevalence, much lower estimates were associated with the requirements of asymmetry of signs and response to medication. The assessment of these clinical features may not be practical in community studies. Impaired postural reflexes, as a cardinal sign, seemed superfluous. For community studies of PD, we recommend the following diagnostic criteria: at least two of resting tremor, bradykinesia, or rigidity, in the absence of other apparent causes of parkinsonism.

Age Distribution↗
PubMed1996

Multiple defects in type III collagen synthesis are associated with the pathogenesis of abdominal aortic aneurysms.

Confluent skin fibroblast cultures were prepared from 40 patients diagnosed with and surgically treated for an abdominal aortic aneurysm. An analysis of secreted type I and type III collagen in the media of these fibroblast preparations revealed reduced secretion of type III collagen from six patients. DNA sequence analysis of the entire coding domain of the pro alpha 1 (III) collagen mRNA in skin fibroblast RNA from these six patients revealed a C to T substitution at nucleotide 607 in one of the probands that would result in the replacement of a leucine residue with phenylalanine in the second position of the first tripeptide repeat in the triple-helical domain of type III collagen. Allele-specific hybridization analysis of genomic DNA from this proband and family members indicated that this non-glycine substitution probably contributed to the aneurysmal phenotype in this patient. No coding sequence mutations were found in the other five patients. It is clear from this study, therefore, that aberrant synthesis of type III collagen, as a consequence of both a coding sequence mutation and other factors contributing to reduced secretion of type III procollagen, will result in the development of an aortic aneurysm in a significant percentage of patients with this disease.

Age of Onset↗
PubMed1996

Altered expression of bcl-2 and bax mRNA in amyotrophic lateral sclerosis spinal cord motor neurons.

One of the primary neurodegenerative events occurring in amyotrophic lateral sclerosis (ALS) is the selective loss of spinal cord alpha motor neurons. To study the potential role of apoptosis in the degeneration of these motor neurons, in situ hybridization was used to measure the expression of two apoptotic cell death genes, bcl-2 and bax, in control and ALS lumbar spinal cord sections. The strongest hybridization signal for bcl-2 mRNA in neurological and nonneurological control spinal cords was found primarily in lamina IX alpha motor neurons, while a weaker hybridization signal was found in neurons of Clarke's nucleus and the proper sensory nucleus of the dorsal horn. Surviving lamina IX motor neurons in ALS spinal cord sections also expressed bcl-2 mRNA, but at levels that were significantly and selectively decreased (4.7-fold) compared with controls. bax mRNA hybridization signal was detected in several cells throughout the gray matter in control and ALS lumbar spinal cord, but was significantly and selectively increased (2.8-fold) in ALS motor neurons. Given the proposed interactive roles of these genes in apoptosis, the present findings favor a scenario in which this mode of cell death would contribute to spinal cord motor neuron degeneration in ALS.

Adult↗
PubMed1996

Occupation, education, and Parkinson's disease: a case-control study in an Italian population.

Current epidemiologic data on the association between occupational exposures and Parkinson's disease (PD) are inconsistent. In a case-control study, we investigated the associations between occupation and PD and between education and PD. The cases (n = 62) were those identified in a prevalence survey (door-to-door, two-phase) of three Sicilian municipalities, as a November 1, 1987. We then randomly selected from the general population two controls for each case, matched for age ( +/- year), sex, and municipality (n = 124). Information on current and past occupations and education for cases and controls was obtained during the survey. Subjects who worked for most of their lives as farmers were not at increased risk of PD (OR = 0.6; 95% CI = 0.3-1.3). Neither were subjects who worked for most of their lives in other occupations (e.g., housewives, fishermen, factory workers, salesmen, craftsmen, clerks). PD was not associated with low education. Our findings suggest that farming, as a broad occupational category, does not play a major role in the causation of PD.

Adult↗
PubMed1996

Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders.

We investigated the validity and reliability of diagnoses made by eight neuropathologists who used the preliminary NINDS neuropathologic diagnostic criteria for progressive supranuclear palsy (PSP) and related disorders. The specific disorders were typical, atypical, and combined PSP, postencephalitic parkinsonism, corticobasal ganglionic degeneration, and Pick's disease. These disorders were chosen because of the difficulties in their neuropathologic differentiation. We assessed validity by measuring sensitivity and positive predictive value. Reliability was evaluated by measuring pairwise and group agreement. From a total of 62 histologic cases, each neuropathologist independently classified 16 to 19 cases for the pairwise analysis and 5 to 6 cases for the group analysis. The neuropathologists were unaware of the study design, unfamiliar with the assigned cases, and initially had no clinical information about the cases. Our results showed that with routine sampling and staining methods, neuropathologic examination alone was not fully adequate for differentiating the disorders. The main difficulties were discriminating the subtypes of PSP and separating postencephalitic parkinsonism from PSP. Corticobasal ganglionic degeneration and Pick's disease were less difficult to distinguish from PSP. The addition of minimal clinical information contributed to the accuracy of the diagnosis. On the basis of results obtained, we propose clinicopathologic diagnostic criteria to improve on the NINDS criteria.

Aged↗