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Biomedical subjects

C Harrington

Publications and source records attributed to C Harrington.

At least 55 records · Page 3Linked to original sources
PubMed1999

Evaluation of polymorphisms in the presenilin-1 gene and the butyrylcholinesterase gene as risk factors in sporadic Alzheimer's disease.

The E4 allele of the apolipoprotein E gene (APOE) is a major risk factor for late-onset Alzheimer's disease (LOAD) but is neither necessary nor sufficient to cause the disease. In this study, we investigated polymorphisms in the presenilin-1 (PS-1), and butyrylcholinesterase (BChE) genes, which have been implicated as risk factors for LOAD. Our data-set comprised 177 AD and 118 control patients, all of whom had been histopathologically confirmed following autopsy. We have tested homozygosity for the PS-1 allele 1 and possession of the BChE-K variant in association with APOE epsilon4 as risk factors in LOAD. Our findings support an association between the PS-1 polymorphism and LOAD, finding homozygosity for allele 1 associated with an approximately two-fold increased risk. Our data also show that in subjects greater than 75 years of age possession of both BChE-K and APOE-epsilon4 alleles is associated with an increased risk of LOAD, whilst the risk associated with APOE-epsilon4 allele alone is not significant.

Aged↗
PubMed1999

The regulation and enforcement of federal nursing home standards, 1991-1997.

This article reports historical trend data on resident characteristics and conditions, problems, and deficiency patterns for nursing facilities from 1991 through 1997 from Health Care Financing Administration (HCFA) administrative records from the On-Line Survey, Certification, and Reporting System (OSCAR). Over this period, residents show some increases in dependency and conditions, although there was a decline in the use of restraints. The deficiencies reveal continued quality problems in some nursing homes, although the average number of deficiencies given to facilities declined by 44 percent between 1991 and 1997. The discussion considers possible explanations for the decline in deficiencies, including whether the quality of care in nursing homes has improved or whether the enforcement process has gradually been weakened.

Activities of Daily Living↗
PubMed1999

Structure and implementation of comprehensive state preadmission screening programs for nursing home applicants: 1978-1994.

This paper examines the structure and implementation of comprehensive state preadmission screening (PAS) programs for nursing home applicants from 1978 to 1994 in all 50 states and the District of Columbia. A state was considered to have comprehensive PAS if a majority of nursing home applicants were screened in-person by state or contract agency staff. Twenty-six states had implemented these programs by 1994, with the most growth taking place during the 1980s. The primary changes in program structure were an increased reliance on private providers to screen a subset of applicants and a higher percentage of states screening private pay applicants. All programs but one referred or authorized the use of community-based services, while most programs diverted well over 10 percent of nursing home applicants.

Case Management↗
PubMed1999

Trends and issues in the Medicaid 1915(c) waiver program.

Over the past 15 years, Medicaid 1915(c) home and community-based waivers have made a substantial contribution to States' efforts to transform their long-term care (LTC) systems from largely institutional to community-based systems. By 1997, every State had implemented a waiver program for at least some subgroups of individuals with disabilities, and expenditures increased from $3.8 million in 1982 to more than $8.1 billion in 1997. Emerging, as well as long-standing, policy issues related to the waiver program include concerns with access, variation in availability by disability group, State decisions related to the provision of community-based LTC, and evidence on effectiveness.

Community Health Services↗
PubMed1998

Examination of the validity of the hierarchical model of neuropathological staging in normal aging and Alzheimer's disease.

The neuropathological staging model of Alzheimer's disease proposed by Braak and Braak [Acta Neuropathol (1991) 82:259] requires that the evolution of neurofibrillary pathology follows a predictable pattern that can be ordered in a regular regional hierarchy. We have operationalized the neuropathological staging system to permit testing of its validity. Forty-two cases were derived from an epidemiological study of cognitive function in an elderly population for which post-mortem brain tissue was collected. Cases with neuropathological diagnoses other than Alzheimer's disease and normal aging were excluded. Neurofibrillary tangle counts were determined in all cortical laminae and regions used for staging. There was a significant correlation between the overall extent of neurofibrillary pathology and the number of regions affected. There were frequent order violations in the proposed hierarchy: 19 instances (45%) involving entorhinal and transentorhinal cortices, and 16 instances (38%) involving CA1 of hippocampus and entorhinal cortex. Only 6 out of 42 cases conformed in all regions to the expected hierarchy. Nevertheless, 90% of the cases had 2 order violations or less, supporting the approximate validity of the hierarchy.

Aging↗
PubMed1997

The identification and characterization of a G4-DNA resolvase activity.

There is increasing evidence that four-stranded Hoogsteen-bonded DNA structures, G4-DNA, play an important role in cellular processes such as meiosis and recombination. The Hoogsteen-bonded G4-DNA is thermodynamically more stable than duplex DNA, and many guanine-rich genomic DNA sequences with the ability to form G4-DNA have been identified. A protein-dependent activity that resolves G4-DNA into single-stranded DNA has been identified in human placental tissue. The resolvase activity was purified from any apparent nuclease activity and is dependent on NTP hydrolysis and MgCl2. Resolvase activity is optimal with 5 mM MgCl2. The Vmax/Km of ATP is 0. 055%/min/microM, higher than the Vmax/Km of the other dNTPs. The products of the resolvase reaction are unmodified single-stranded DNA. The resolvase is not a duplex DNA helicase or a topoisomerase II activity and does not unwind Hoogsteen-bonded triplex DNA. Resolvase is a novel activity that unwinds stable G4-DNA structures using a dNTP-dependent mechanism producing unmodified single-stranded DNA. Potential in vivo roles for this G4-DNA resolvase activity are discussed.

Chromatography, Gel↗
PubMed1997

Eucaryotic DNA primase does not prefer to synthesize primers at pyrimidine rich DNA sequences when nucleoside triphosphates are present at concentrations found in whole cells.

The critical role of NTP concentration in determining where calf thymus DNA primase synthesizes a primer on a DNA template was examined. Varying the concentration of NTPs dramatically altered the template sequences at which primase synthesized primers. At the low NTP concentrations typically used for in vitro experiments (100 microM), primase greatly preferred to synthesize primers at pyrimidine rich DNA sequences. However, when the concentrations of NTPs were increased to levels typically found in whole cells, primers were now synthesized in all regions of the template. Importantly, synthesis of primers in all regions of the DNA template, not just the pyrimidine rich sequences, is the pattern of primer synthesis observed during DNA replication in whole cells. With low concentrations of NTPs (i.e., Vmax/K(M) conditions), primers are only synthesized at the most preferred synthesis sites, namely, those that are pyrimidine rich. In contrast, under conditions of high NTP concentrations, primer synthesis will occur at the first potential synthesis site to which primase binds. Now, the primase x DNA complex will be immediately converted to a primase x DNA x NTP x NTP complex that is poised for primer synthesis.

Adenosine Triphosphate↗
PubMed1997

Microsatellite polymorphism of the alpha 1-antichymotrypsin gene locus associated with sporadic Alzheimer's disease.

A variant of the apolipoprotein E gene, APOE*4, is associated with both sporadic Alzheimer's disease (AD) and a subset of familial AD and this association is stronger with early as opposed to late onset AD. Both APOE*4 and alpha 1-antichymotrypsin (ACT) will accelerate the rate of amyloid filament formation and are major constituents of the plaques associated with AD. We now show that a dinucleotide microsatellite allele in the 5'-flanking sequence of the ACT gene, designated A10, in association with APOE*4 significantly increases the risk of developing sporadic AD, which accounts for the majority of AD cases.

Aged↗
PubMed1997

The effect of certificate of need and moratoria policy on change in nursing home beds in the United States.

OBJECTIVES: This study examined the effects of state certificate of need and/or moratorium requirements on the change in nursing home bed growth in states over a 13-year period. METHODS: Data were collected from five telephone surveys of state officials about state certificate of need and moratorium policies, state Medicaid nursing home reimbursement rates, and the licensed nursing home beds in each state for the 1979 through 1993 period. Two-stage least squares regression analysis treated certificate of need and/or moratorium and Medicaid reimbursement rates as endogenous variables in predicting the change in nursing home beds per aged population in states. RESULTS: States that had a certificate of need and/or moratorium did have significant reductions in the growth in nursing home beds but Medicaid nursing home reimbursement rates were not related to change in bed stock. The percentage of the population living in a metropolitan area, the personal income per 1,000 population, the percent unemployed, a state's tax effort, and time were positively associated with change in nursing home beds. The ratio of nursing home beds per 1,000 aged population in the previous year was a negative predictor of change in bed stock in a given year. CONCLUSIONS: State regulatory policies have an effect on bed growth in contrast to reimbursement policies.

Certificate of Need↗
PubMed1997

State-imposed limits on Medicaid reimbursement for nursing facility care.

OBJECTIVES: Nursing cost-center limits were examined, along with their effects on Medicaid. METHODS: A national survey of Medicaid nursing facility reimbursement provided data on cost centers for nursing, administration, and capital, whether in specific, larger, or multiple cost centers. RESULTS: Most states impose nursing and administration limits. Far fewer states impose capital limits, but only capital limits may be related to constraint of reimbursement rates. CONCLUSIONS: Shifting toward limiting capital costs, or simply eliminating cost-center limits, might accommodate cost control while removing negative constraints on direct resident care.

Cost Allocation↗
PubMed1997

The diagnosis and treatment of post-stroke depression.

Depression is common after stroke but the diagnosis may be difficult. Anterior and subcortical brain lesions increase the risk of depression. It is important to make an accurate diagnosis of PSD as treatment may reduce morbidity. Treatment should consist of family support, education and anti-depressant medication.

Aged↗
PubMed1997

Initiation and regulation of CNS autoimmunity.

Our studies addressed the questions of how self-reactive T cells escape tolerance and what stimuli cause these T cells to initiate autoimmune responses. We employed experimental allergic encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). Endogenous expression of myelin basic protein (MBP) induces tolerance in T cells that recognize one region of MBP, whereas T cells specific for a different region escape tolerance. Triggers of disease induction were investigated in a T-cell receptor (TCR) transgenic model in which the majority of T cells recognize the MBP epitope that does not induce tolerance. EAE occurs spontaneously in this model and the incidence of disease depends on microbial exposure. EAE can also be actively induced by immunization with MBP peptide accompanied by injection of pertussis toxin as well as by administration of pertussis toxin alone. Immunization with MBP peptide without pertussis toxin, however, stimulates the transgenic T cells, but the activated T cells do not accumulate in the central nervous system (CNS) or induce EAE. Our studies suggest that initiation of autoimmune disease involves complex interactions between the neuroendocrine system as well as the innate and specific immune systems.

Animals↗
PubMed1996

Hepatitis A vaccine responses in HIV-positive persons with haemophilia.

The safety and immunogenicity of subcutaneously (s.c.) administered hepatitis A (HA) vaccine was evaluated in HIV positive and negative patients with haemophilia and healthy male controls. The vaccine was well tolerated. Seroconversion occurred among all controls after one dose of vaccine but was delayed among patients, particularly if HIV-positive-4 of 17 (24%) failed to respond to three doses of vaccine. Following the third dose of vaccine, geometric mean titres were significantly higher among controls (1354) than among HIV infected patients (204) (P < 0.05). Non-responders failed to develop an immune response following boosting with high titre vaccine. Patients with haemophilia may be vaccinated against HA s.c. but consideration should be given to ensuring that HIV-positive individuals with haemophilia and other immunosuppressed individuals should have their immune responses checked since additional booster doses or passive prophylaxis may be necessary in such individuals.

Adolescent↗