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Biomedical subjects

K Bell

Publications and source records attributed to K Bell.

At least 91 records · Page 5Linked to original sources
PubMed1995

Clinical correlates of Alzheimer's disease with and without silent radiographic abnormalities.

OBJECTIVE: To determine whether patients with Alzheimer's disease (AD) who do not have historical or clinical evidence of stroke but who do have computed tomographic or magnetic resonance imaging evidence of noncortical lesions smaller than 2 cm or periventricular "caps" differ from other patients with AD. METHODS: The computed tomographic or magnetic resonance imaging scans of 158 patients meeting criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD were reviewed by one neuroradiologist. Two measures of disease severity--the Modified Mini-Mental State examination and the Blessed Dementia Rating Scale (Part I)--were subjected to two-way analysis of variance with scan type (computed tomography or magnetic resonance imaging) and lesion number as between-group factors and age and disease duration as covariates. RESULTS: No relationship was seen between lesion number or periventricular caps and disease severity. CONCLUSION: In this cross-sectional analysis using these clinical measures, patients with AD who have well-defined radiographic abnormalities cannot be differentiated from patients with AD who do not have them.

Adult↗
PubMed1995

Neuropsychologic impairment in early HIV infection. A risk factor for work disability.

OBJECTIVE: To explore the functional significance of incident neuropsychologic impairment among initially asymptomatic subjects infected with human immunodeficiency virus. DESIGN: Prospective, observational cohort study of homosexual and bisexual men to examine the incidence of work disability related to the onset of neuropsychologic impairment. SETTING: A university clinical and behavioral research site in New York City. PARTICIPANTS: Sample of 207 homosexual and bisexual men; 123 were seropositive and 84 were seronegative. PRINCIPAL OUTCOME MEASURES: Incident work disability in the course of 4.5 years of follow-up, with disability defined as a persistent (> or = 24 months) change in work hours (from 20 or more to less than 20 h/wk). RESULTS: Compared with seronegative control subjects (n = 72), the relative risk of work disability among initially asymptomatic seropositive men (n = 44) was 2.76 (95% confidence interval, 1.2 to 6.5), nearly a threefold increase. Proportional hazards models show that this increased risk is attributable to the development of major neuropsychologic impairment in a subset (eight of 44) of the initially asymptomatic men, which is significantly associated with incident work disability (6/8 [75%]). Adjusting for symptom status and CD4+ cell count at the time of disability did not eliminate the increased risk associated with neuropsychologic impairment. CONCLUSIONS: In this cohort, the increased risk of work disability among initially asymptomatic human immunodeficiency virus-positive men was related to incident neuropsychologic impairment; such impairment predicted work disability independently of symptom status and CD4+ cell count over the follow-up period. Neuropsychologic impairment in the course of human immunodeficiency virus infection may indicate increased risk for poor outcomes over and above that associated with systemic disease.

Cohort Studies↗
PubMed1995

A standardized technique for establishing onset and duration of symptoms of Alzheimer's disease.

OBJECTIVES: To develop an informant-based semistructured interview to determine the onset and duration of symptoms of Alzheimer's disease, and to use this instrument with informants to characterize a cohort of mildly impaired patients with Alzheimer's disease. DESIGN: In study 1, interrater and interinformant reliability was examined for the date of onset and the order of appearance for specific symptoms that were elicited by the semistructured onset interview. In study 2, the instrument was used to characterize disease onset in a cohort of patients with Alzheimer's disease who were participating in a large multicenter study. SUBJECTS: Informants of patients with Alzheimer's disease. RESULTS: In study 1, interrater reliability for duration of illness was excellent (intraclass correlation coefficient = .99, P < .001), and interinformant reliability was good (intraclass correlation coefficient = .86, P < .001). Agreement for the presence of a given symptom was highest for those that were most commonly reported (eg, memory and performance difficulty). In study 2, 89% of the cohort had memory problems, and 63.9% had performance difficulties as the first or second symptom. Depression and language problems were less commonly reported. Psychosis and behavioral disturbances were rarely reported as the first problem. CONCLUSION: This instrument provides a reliable procedure for standardizing the estimation of duration of illness based on retrospective report.

Aged↗
PubMed1995

Risk of human immunodeficiency virus type 1-related neurologic disease in a cohort of intravenous drug users.

BACKGROUND: Although the proportion of cases of acquired immunodeficiency syndrome related to intravenous drug use has increased dramatically over the past decade, there has been no longitudinal examination of primary neurologic disease in this group. OBJECTIVE: To study the development of neurologic disease in human immunodeficiency virus (HIV)-negative and HIV-positive men and women who were intravenous drug users over a 3.5-year period. DESIGN: Prospective observational cohort study. SETTING: Subjects were recruited from an infectious disease clinic at a New York City Hospital or from a methadone maintenance program. PARTICIPANTS: Ninety-nine HIV-negative (62 men and 37 women) and 124 HIV-positive (85 men and 39 women) intravenous drug users volunteered. MAIN OUTCOME MEASURE: The development of clinically significant manifestations in six neurologic domains. RESULTS: With multivariate adjustment for current and past substance abuse, age, education, and head injury, we examined the odds of developing HIV-related neurologic disease. Extrapyramidal signs and reduced motor ability became increasingly apparent over time in HIV-infected men as their CD4 cell count declined and as the subjects developed the acquired immunodeficiency syndrome. Fewer neurologic signs were seen in the women. CONCLUSIONS: The impact of HIV infection among intravenous drug users parallels that in homosexual men and is independent of alcohol and other drug use.

Adult↗
PubMed1995

GABAergic projection from the ventral pallidum and globus pallidus to the subthalamic nucleus.

There exists a topographically organized projection from the globus pallidus and ventral pallidum to the subthalamic nucleus and adjacent lateral hypothalamus. The participation of GABA as a neurotransmitter in this projection was evaluated by retrograde labeling of cells in the pallidal area from an iontophoretic deposit of Fluor-Gold in the subthalamus combined with in situ hybridization for mRNA of the GABA synthetic enzyme, glutamate decarboxylase (GAD). A rostrocaudal gradient in the contribution of GABA to the projection was demonstrated with a relatively small percentage of retrogradely labeled cells in the rostral ventral pallidum containing GAD mRNA (7%) compared to the caudal globus pallidus which had over 70% of the Fluoro-Gold containing cells double-labeled for GAD mRNA. Overall the ventral pallidum contribution to the subthalamic nucleus was less GABAergic than the portion arising from the globus pallidus (35% vs. 61%, respectively).

Animals↗
PubMed1995

A generic method for expression and use of "tagged" soluble versions of cell surface receptors.

A general method for expression, purification, immobilization, detection and radiolabeling of extracellular domains (ECD) of type I membrane proteins. The type I interleukin-1 receptor (IL-1RtI), the alpha-subunit of interleukin-2 receptor (IL-2R alpha) and E-selectin are used as illustrative examples of cell surface receptors. DNA encoding the ECD of the proteins are fused at their 3' end to a chimeric DNA which serves to generically "tag" the recombinant ECD. The resulting fusion protein contains a substrate sequence for protein kinase-A (PKA) adjacent to the signal sequence from human placental alkaline phosphatase (HPAP), The HPAP signal sequence directs the formation of the phosphatidylinositol-glycan (PI-G) anchorage of the protein at the cell surface. When these chimeric genes are expressed in CHO cells, the ECDs are detected on the cell surface and can be released by treatment with phosphatidylinositol-specific phospholipase-C (PI-PLC). Based on protein processing known to occur for native HPAP, twenty amino acids from the HPAP signal sequence remain at the C-terminus of the ECD. A high affinity monoclonal antibody was generated against this common epitope. This antibody can be used to detect, purify and immobilize the ECDs. In addition, the ECDs can be radiolabeled with 32P by treatment with PKA and maintain the ability to bind their natural ligands. This "tagging" method has been successfully applied to many other type I proteins which serve as cell surface receptors.

Alkaline Phosphatase↗
PubMed1995

Mutations in the equine plasma transferrin and esterase systems.

Eleven apparent mutations of the equine plasma transferrin and esterase gene (10 in TF and one in ES) were found in an analysis of approximately 240,000 thoroughbred horses. Eight of the transferrin mutations produced variants not previously recognized in horses. In the two remaining transferrin mutations and the esterase mutation, reduced plasma concentrations of the proteins were demonstrated by immunological techniques and together with the family data indicated the existence of 'null' alleles.

Animals↗
PubMed1995

Consistency of clinical diagnosis in a community-based longitudinal study of dementia and Alzheimer's disease.

We evaluated the consistency of the diagnosis of dementia in a multicultural, longitudinal community-based study of cognitive impairment and dementia. We diagnosed dementia using a fixed neuropsychological paradigm; the diagnosis also required historical evidence of functional impairment. In a sample of 656 subjects with at least one annual follow-up examination, dementia was confirmed at 1 year in 89% of the 304 subjects initially demented, and in 90% of the 136 subjects with the initial diagnosis of probable Alzheimer's disease (AD). The 34 initially demented subjects who failed to meet criteria for dementia at follow-up included 13 with an initial diagnosis of probable AD. All 34 still had evidence of cognitive impairment; this group was more likely to have a history of pulmonary disease, multiple medication use, or chronic alcohol use than other demented patients. Consistency of dementia diagnosis did not vary according to educational attainment or ethnic background. The use of a neuropsychological paradigm such as ours in large longitudinal studies of dementia may minimize interobserver diagnostic variability or diagnostic drift over time while contributing the benefits of a comprehensive cognitive evaluation to the diagnostic process.

Aged↗
PubMed1995

Neurologic signs and symptoms in a cohort of homosexual men followed for 4.5 years.

We traced the development of neurologic impairment in 207 homosexual men (123 human immunodeficiency virus [HIV]-positive and 84 HIV-negative controls) over 4.5 years of follow-up. We applied generalized estimating equations to logistic regression analyses with repeated measures to examine the differences between HIV-positive and HIV-negative subjects with respect to the likelihood of developing six neurologic outcomes derived from a factor analysis, significant neurologic impairment (modified Kurtzke disability score of > or = 3), or significant neuropsychological impairment. We found that, over time, HIV-positive subjects were more likely to develop clinically significant extrapyramidal signs and frontal release signs than HIV-negative subjects. Controlling for age or education, as CD4 count declined, the odds of developing significant extrapyramidal signs, abnormalities in alternating movements, frontal release signs, and a Kurtzke score > or = 3 increased. HIV-positive subjects were almost five times as likely (odds ratio [OR], 4.6; 95% CI, 1.6 to 13.4) as HIV-negative subjects to stay the same or worsen neurologically on the next visit, and those with CD4 < or = 200 were 4.8 times as likely (OR, 4.8; 95% CI, 2.2 to 10.7) to maintain or worsen neurologically relative to those with higher CD4 counts. We conclude that neurologic impairment becomes increasingly apparent over time in HIV-infected men, especially in those with low CD4 counts.

Adult↗
PubMed1994

A coordinated, communitywide program in Monroe County, New York, to increase influenza immunization rates in the elderly.

BACKGROUND: Despite the efficacy of influenza vaccination in preventing complications of influenza, rates of immunization among high-risk populations remain low. The Monroe County (New York) Influenza Vaccination Demonstration was a communitywide, collaborative effort to increase the rates of influenza immunization to greater than 60% in elderly Medicare recipients. METHODS: The local health department, university medical center, and practicing physicians collaborated to develop a communitywide demonstration directed to all Medicare part B enrollees 65 years of age or older, multiple coordinated approaches were used over a 4-year period (1988 to 1992). Most providers, including public agencies, private providers, hospital outpatient facilities, nursing homes, and insurance providers, were enrolled in a comprehensive program that included centralized claims processing, vaccine distribution and promotion, and extensive provider and public education efforts, including a special urban outreach program. An office-based, denominator-driven physician incentive project was also evaluated. RESULTS: The demonstration project resulted in a 1991 influenza immunization rate of 74.3% among 88,811 Medicare enrollees 65 years of age or older. The increase in immunization rate occurred primarily among the patients of private physicians. CONCLUSION: A communitywide, collaborative approach can succeed in achieving high rates of influenza immunization.

Aged↗
PubMed1994

Blood protein polymorphisms in the donkey (Equus asinus).

Transferrin, albumin, 6-phosphogluconate dehydrogenase and vitamin D-binding protein polymorphisms were detected in 242 feral and domesticated Australian donkeys by polyacrylamide gel electrophoresis, starch gel electrophoresis, autoradiography, immunoblotting with specific antisera and activity staining. All four TF and two ALB variants were donkey specific while only one of the PGD variants was donkey specific. The two GC variants were electrophoretically identical to the Equus caballus F and S proteins. Available evidence suggested that the TF, ALB, PGD and GC systems are controlled by co-dominant alleles with frequencies of the most common alleles of each system being 0.831, 0.946, 0.957 and 0.861 respectively. Glucose phosphate isomerase and plasminogen were monomorphic in the Australian population of donkeys.

Animals↗
PubMed1994

Intrageneric amplification of horse microsatellite markers with emphasis on the Przewalski's horse (E. przewalskii).

Primer sequences flanking 13 microsatellite loci isolated from the domestic horse (E. caballus) were successfully used to amplify homologous loci in the Przewalski's horse (E. przewalskii). The results demonstrate that the level of polymorphism at all 13 loci in the Przewalski's horse was comparable to that in the domestic horse and the overall exclusion probability in the Przewalski's horse was calculated to be 0.9994. The results suggest that it should be possible to use E. caballus-derived microsatellite markers to provide parentage verification and additional valuable information to the captive management of E. przewalskii. The ability to amplify corresponding loci in the remaining five species of the genus was also confirmed, illustrating the general application of markers isolated from the domestic horse to the evaluation of polymorphism in the other six species of the genus.

Animals↗
PubMed1994

Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study.

OBJECTIVE: To examine whether either extrapyramidal signs or psychotic features are associated with more rapid progression of Alzheimer's disease. BACKGROUND: It has been unclear whether extrapyramidal signs and psychosis are predictors of faster course or are simply late signs. METHODS: Two hundred thirty-six patients with mild Alzheimer's disease were recruited in three cities and followed semiannually. RESULTS: Using Cox proportional hazards models that adjusted for age, sex, disease severity, and estimated duration of illness at study entry, the presence of extrapyramidal signs at entry was associated with higher relative risk (RR) of reaching moderate cognitive (RR = 2.35, 95% CI = 1.12 to 4.92) or functional (RR = 2.31, 95% CI = 1.37 to 3.90) severity, nursing home entry (RR = 2.51, 95% CI = 1.32 to 4.76), or death (RR = 3.04, 95% CI = 1.31 to 7.05). Psychosis predicted only the functional end point (RR = 1.85, 95% CI = 1.18 to 2.90). Using regression models, modified Mini-Mental State scores declined 1.30 points (95% CI = 0.16 to 2.44) per 6-month interval, more among patients with than those without extrapyramidal signs; patients with psychosis declined 1.15 (95% CI = 0.52 to 1.77) more mMMS points per interval. CONCLUSIONS: This study confirms extrapyramidal signs and psychosis as robust predictors of disease end points and rapid progression in Alzheimer's disease.

Age Factors↗
PubMed1994

Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline.

We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimer's disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills.

Age of Onset↗