Biomedical subjects
Publications and source records attributed to C Harrington.
Role restructuring can be the key to maximizing efficiency, productivity, and operational effectiveness. The clinical nurse specialist role was restructured from a divisional project focus to a unit-based design to enhance the care of specific patient populations. The authors describe the process used to make this change, the outcomes achieved, and the lessons learned.
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Health plan satisfaction among the elderly is affected by multiple individual and locational factors. We used a general behavioral framework of predisposing, enabling, and service use factors to produce adjusted satisfaction scores. These then were included in a logistic analysis to determine the effect of satisfaction on continued membership in social health maintenance organizations (S/HMOs) or continued participation in fee-for-service care. S/HMO members, after one year in the plan, generally reported satisfaction scores comparable to Medicare beneficiaries in fee-for-service care. Satisfaction with perceived physician quality and interpersonal relationships with the providers reduced the risk of disenrollment. Functional impairment reduced the likelihood of disenrollment, but this effect varied by community. Being impaired was protective in communities with established HMOs. In markets where HMOs were emerging or where intensive HMO competition was beginning, disability increased the likelihood of changing current coverage. S/HMO membership, after adjusting for the market area's general disenrollment propensities, had varying effects. Being a newly formed plan was not a consistent predictor of higher disenrollment rates.
Cholinergic muscarinic receptor genes are members of the G-protein receptor gene superfamily. In this study we describe the structure of the gene and promoter of the rat m4 muscarinic receptor gene. A rat cosmid clone containing the coding region for the m4 gene and 25 kilobases of upstream sequence was isolated. This clone directed expression of the rat m4 gene when introduced in IMR32 cells, a human neuroblastoma that expresses m4, but did not drive expression when introduced into Chinese hamster ovary cells, a line that does not express the m4 gene. S1 nuclease, modified 5'-rapid amplification of cDNA ends and polymerase chain reaction analysis of rat cosmid DNA and cDNA showed that the gene consists of a 2.6-kilobase coding exon, extending 34 base pairs (bp) upstream from the initiating ATG, separated from a 460-493 bp noncoding exon by a 4.8-kilobase intron. DNA sequence analysis shows that the non-coding exon is GC-rich and that the promoter does not contain a TATA or CAAT box and has several consensus sequences for enhancer elements including five Sp-1 binding sites, one AP-2 site, one AP-3 binding site and two E-boxes within the proximal 600 bp. A reporter construct consisting of 1440 bp of flanking DNA and 80 bp of the first exon cloned into a luciferase reporter plasmid, drove cell specific expression in transient transfection assays. Removal of 1088 bp of the 5' end of this construct resulted in expression in non-m4 expressing cell lines suggesting there is a repressor element in this region.
Oligonucleotides containing a specific initiation site for polymerase alpha-primase (pol alpha-primase) were used to measure the effects of cytosine arabinoside triphosphate and cytosine arabinoside monophosphate (araCMP) in DNA on RNA-primed DNA synthesis. Primase inserts araCMP at the 3' terminus of a full-length RNA primer with a 400-fold preference over CMP. The araCMP is elongated efficiently by pol alpha in the primase-coupled reaction. Extension from RNA 3'-araCMP is 50-fold less efficient than from CMP, and extension from DNA 3'-araCMP is 1600-fold less efficient than from dCMP. Using araCMP-containing templates, primer synthesis is reduced 2-3-fold, and RNA-primed DNA synthesis is reduced 2-8-fold. The efficiency of polymerization past a template araCMP by pol alpha is reduced 180-fold during insertion of dGMP opposite araCMP and 35-fold during extension from the araCMP:dGMP 3' terminus. These results show that the pol alpha-primase efficiently incorporates araCMP as the border nucleotide between RNA and DNA and suggest that the inhibitory effects of araC most likely result from slowed elongation of pol alpha and less so from inhibition of primer synthesis by primase.
The initiation of new DNA strands at origins of replication in animal cells requires de novo synthesis of RNA primers by primase and subsequent elongation from RNA primers by DNA polymerase alpha. To study the specificity of primer site selection by the DNA polymerase alpha-primase complex (pol alpha-primase), a natural DNA template containing a site for replication initiation was constructed. Two single-stranded DNA (ssDNA) molecules were hybridized to each other generating a duplex DNA molecule with an open helix replication 'bubble' to serve as an initiation zone. Pol alpha-primase recognizes the open helix region and initiates RNA-primed DNA synthesis at four specific sites that are rich in pyrimidine nucleotides. The priming site positioned nearest the ssDNA-dsDNA junction in the replication 'bubble' template is the preferred site for initiation. Using a 40 base oligonucleotide template containing the sequence of the preferred priming site, primase synthesizes RNA primers of 9 and 10 nt in length with the sequence 5'-(G)GAAGAAAGC-3'. These studies demonstrate that pol alpha-primase selects specific nucleotide sequences for RNA primer formation and suggest that the open helix structure of the replication 'bubble' directs pol alpha-primase to initiate RNA primer synthesis near the ssDNA-dsDNA junction.
BACKGROUND: The social health maintenance organization (S/HMO) demonstration was implemented, in part, to determine if the presumed integration of acute and chronic care in these plans could produce sufficient savings to allow plans to offer expanded and chronic care benefits without increased cost to the Medicare program. METHODS: S/HMO members and a sample of fee-for-service (FFS) recipients were tracked over three years to assess their utilization experience. Analyses controlled for case mix, using Grade of Membership procedures. RESULTS: In 1987, the last year of risk sharing, S/HMOs reported higher total expenditures than FFS in each health status class. For the "healthy," differences were largest for physician care. In other classes, differences in nonskilled nursing or home care use were noted. In 1988, the first year of full risk, Seniors Plus had equivalent or lower expenditures relative to FFS for all classes. Elderplan had lower expenditures in four of six classes and provided more service to the "frail" and the "acutely ill." SHP had higher expenditures in all classes because of higher hospital and nursing home expenditures. Medicare Plus II had higher expenditures in all classes, for physician, nonskilled nursing home, and home care expenditures. CONCLUSIONS: Overall plan losses and higher expenditures among a number of case mix groups suggest a need for refinement of S/HMO operations--especially in case management relationships to medical care and in the selection of "high risk" cases.
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The evaluation of long-term care demonstrations has to deal with complex organizational entities, with large, heterogeneous client populations that, during the course of study, may have to change features of their organization or operation. The implications of such "real-time" changes are discussed for analyses of the operation and performance of Social/Health Maintenance Organizations over a 5-year period (2 years of start-up and enrollment and 3 years of follow-up). Analyses conducted of the plans in the context of real-time changes have to be based on different statistical models than for classic experimental study designs, where treatment factors are fixed rather than dynamic. A number of issues that may arise are identified, and possible approaches to their solutions described. Key words: long-term care; demonstrations; evaluations; study design; capitation.
A high-performance liquid chromatographic (HPLC) method was developed for the quantitative, simultaneous determination of the following four compounds in serum: E-doxepin, Z-doxepin, E-desmethyldoxepin, and Z-desmethyldoxepin. A 3-microns analytical silica column (6 x 100 mm) was employed with the mobile phase 0.025 M phosphate:acetonitrile:n-nonylamine (80:20:1). This HPLC method allows for the accurate measurement of all four isomeric compounds.
Access by older persons to nursing home care is a major concern. Turmoil in the health care industry in the 1980s worsened access problems, including waits for admission, already severe at the start of the decade. This paper examines waits for nursing home admission, relating them to facility and market factors.
The demand for nursing facility (NF) beds has been growing with the aging of the population and many other factors. As the need for nursing home care grows, the Nation's capacity to provide such care is the subject of increasing concern. This article examines licensed NFs and beds, presenting data on trends from 1978-93. Measures of the adequacy of NF beds in States are examined over time, including the ratio of beds per aged population, occupancy rates, and State official's opinions of the adequacy of supply. State and regional variations are shown over time, and we speculate on the factors which may be associated with the variation.
Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.
A multivariate procedure for identifying case-mix dimensions from discrete health variables is presented. Since the dimensions are generated only from health use data and not service use data, they can be used for adjust capitation rates to provide incentives to treat persons not currently well integrated in standard health care system (e.g., very ill persons, the uninsured) or to promote specific health outcomes. The procedure is illustrated with data from Social/Health Maintenance Organizations (S/HMO) since they provide both acute and long-term care (LTC) services. Thus, case-mix measures to adjust S/HMO reimbursements have to represent both medical conditions and the degree, and type, of functional impairment. From 31 health and functioning items, six case-mix dimensions, and scores for individuals on each, were calculated. The multivariate distribution of scores in S/HMO enrollees, and in Medicare eligible, comparison samples, were examined in each site to see how their health differed. S/HMO enrollees were healthier and less frail than persons remaining in the Medicare FFS system. Such differences are important in adjusting capitation rates to provide incentive to accept clients with complex health problems.
This article examines the political agendas of public sector and organized private sector interests concerned with policies affecting uncertified home care agencies in three metropolitan areas. Using a telephone survey, the study found substantial differences across these groups in both the frequency with which they work on given issues and in some key attitudes. Overall, respondents were most likely to work on policies related to home care quality, and had particularly diverse--and at times conflicting--concerns in this area. Policymakers need to actively solicit the diverse attitudes of key interest groups towards controversial issues in order to understand less dominant perspectives, keep in mind the interconnection of policy issues, and arrive at politically viable solutions to home care policy problems.
Between May 1983 and September 1991 eleven patients with severe haemophilia underwent splenectomy for HIV-related thrombocytopenia. The sustained complete remission rate (platelets > 100 x 10(9)/l) was 82% over a mean follow-up period of 54 months. The group was compared with 22 age-matched non-thrombocytopenic HIV seropositive haemophiliacs who had not undergone splenectomy. Both groups had equivalent use of factor concentrate and there was no significant difference between the groups in terms of anti-retroviral treatment. Analysis of clinical progression of HIV infection and CD4 positive lymphocyte (CD4+) counts, for the time since splenectomy, revealed no significant difference in progression of HIV infection in the splenectomized group compared with the control group. It is concluded that splenectomy is an effective treatment for HIV-related thrombocytopenia and has no adverse effect on the progression of HIV infection.
Imipramine and desipramine were structurally modified by the attachment of spacer arms to the aromatic ring which were subsequently attached to bovine serum albumin. This approach utilized novel spacer arms and conjugation methods. This method yielded antisera with excellent selectivity and good titers. Rabbits were used to raise the antisera and the antibodies produced were characterized with respect to their cross-reactivity with imipramine, desipramine and hydroxy metabolites as well as selected structurally related compounds.