Cytotoxic T lymphocytes induced against allogeneic I-region determinants react with Ia molecules on trinitrophenyl-conjugated syngeneic target cells

The major histocompatibility complex codes for determinants which are recognized by and serve as targets for cytolytic T lymphocytes (CTL) (1). Antigens coded for by the K and D loci of the H-2 complex can activate xenogeneic or allogeneic CTL (2,3). In addition, the H-2K or H-2D gene products function as those molecules against which syngeneic CTL responses specific for chemical, viral, and minor H antigens are directed (4-8). It has recently been shown that Ia determinants can also serve as target antigens for distinct but weaker CTL responses (9-13). Those clones which recognize Ia antigens see them independently of K- or D- coded antigens as shown in genetic studies and by antisera-blocking experiments (12,13). We have proposed that the existence of clones of CTL specific for I-region-coded determinants is not fortuitous; rather these clones specifically recognize Ia determinants and may have an immunoregulatory role. These CTL may affect those immune functions which are at least partially dependent on or controlled by I-region-coded molecules. Two predictions can be made and tested concerning the role of Ia determinants in cytolytic systems and the role, if any, of I-region- specific CTL in regulating the immune response: (a) that if as we and others have shown, certain Ia specificities can serve as a third series of major histocompatibility antigens, then Ia antigens should be susceptible to the same types of antigenic modifications as H-2K- or H-2D-coded structures and thus serve as targets for CTL directed against modified-self in selected systems; and (b) that allogeneically induced I-region-specific CTL should demonstrate cross-reactivity with targets bearing modified syngeneic I-region-coded determinants. Data will be present which demonstrates that trinitrophenyl (TNP)-modified syngeneic I-region determinants can serve as targets for CTL induced by allogeneic Ia antigens

Cytotoxic T lymphocytes specific for I region determinants do not require interactions with H-2K or D gene products

Gene products coded for by the major hisocompatibility complex (MHC) can serve as target antigens for cytotoxic T lymphocytes (CTL) (1). A variety of test systems are available which have yielded information consistently reinforcing the importance of this complex of genes in the generation and effector phases of the cytotoxic immune response. Originally, it was shown that allogeneically-induced CTL had specificity primarily for the products of the K and D loci of the mouse H-2 complex (2). More recently this has also been found to be the case for xenogeneic immunizations (3,4). Additional examples of T cell-mediated lysis have been reported involving viral-infected or chemically- modified syngeneic stimulating and target cells in which homology at H-2K or H-2D was required between the responding and target cells for appreciable lysis to occur (5-7). Moreover, CTL specific for minor histocompatability antigens are able to lyse only target cells bearing these membrane antigens and sharing a common H-2K or H2-D gene product with the effector (8,9). Two hypotheses have been proposed to explain the requirement for H-2 identity between effector and targets in these systems. CTL may recognize new antigenic determinants created by the interaction of the modifier with syngeneic K and D gene products. Alternately, a dual recognition system my exist, requiring an antigen-specific receptor as well as a second receptor with specificity for homologous H-2K or H-2D determinants (5). Neither model can be excluded at this time. The I region also contains genes coding for histocompatibility loci since animals differing at the I-A or I-C regions of the H-2 complex reject skin grafts (10-12), though less rapidly than mice differing at the H-2K or H-2D regions, Also CTL can be generated to I region determinants but less efficiently than CTL specific for H-2K or H-2D gene products (12-14). The question can therefore be raised, whether the I region minor histocompatibility loci function independently from the H-2K or H-2D loci or whether I region-specific cytolysis requires the participation of H-2K or H-2D gene products of the target cell. This communication illustrates the generation of CTL showing specificity for I region determinants in primary mixed lymphocyte cultures. Further, we demonstrate by genetic analysis and byt eh use of speficit alloantisera that CTL directed to Ia determinants (a) do not see these antigens as modifications of H-2K or H-2D gene products but as independent gene products coded for by the I region, and (b) they do not require interaction with target cells bearing the same H-2K or H-2D gene product as the effect CTL

Benchmarking Home Health Care and Public Health Nursing Services

Purpose The Billings Area Indian Health Service (IHS) serves approximately 60,021 American Indians living in Montana and Wyoming. For many eligible American Indians in the Billings Area, home health care services are not available. The aims of this project are: 1) develop a current profile of existing public health nursing and home health care services on each reservation in the Billings Area IHS; 2) develop a profile of successful home health programs on reservations in the United States; and 3) integrate the two profiles to identify factors contributing to success and failure in home care programs. Methods Benchmarking, a key tool in Total Quality Management (TQM), was used in this project. Several phases are undertaken in a benchmarking process: planning, analysis, integration, action, and maturity. This project focused on the first three phases. Initially, the project team decided what to benchmark - skilled home health care. Next, profiles of the eight Billings Area IHS Service Units were developed. The project team then visited four sites across the U.S. where tribes provided home health care services to tribal members with partner agencies. Results The user populations of the Billings Area Service Units range from 3,700 to 10,400. The proportion of the population that is elderly has been used as an indicator of home health care need. The populations are relatively young with a high percentage of residents under age 5 and a relatively low percentage of residents over the age of 55. The leading causes of persons using home health care include heart disease, musculoskeletal disease, injuries and poisoning, cancer, respiratory disease and endocrine disorders. The availability of home health care resources on the Service Units varies widely. All Billings Service Units have public health nursing services, however, most the Public Health Nurses are only able to provide minimal home health care services. Tribal home health care partnerships developed by Fort Belknap in Montana, Cherokee Nation in Oklahoma, and the Navajo Nation in New Mexico, were reviewed with respect to service agreements, clients, and budget implications. Conclusion For any new skilled home health care service venture to be successful, the following components must be present: 1) commitment; 2) support; 3) communication; 4) leadership; and 5) autonomy. Prior to implementing a strategy of home health care services, several issues must be considered. These issues include: 1) size of service population; 2) geographic location of service population; 3) availability of collaborator agencies; 4) availability of skilled home health care professionals; 5) administrative capacity; 6) technology infrastructure 7) tribal support; and 8) community networks

An intervention to improve care and reduce costs for high-risk patients with frequent hospital admissions: a pilot study

<p>Abstract</p> <p>Background</p> <p>A small percentage of high-risk patients accounts for a large proportion of Medicaid spending in the United States, which has become an urgent policy issue. Our objective was to pilot a novel patient-centered intervention for high-risk patients with frequent hospital admissions to determine its potential to improve care and reduce costs.</p> <p>Methods</p> <p>Community and hospital-based care management and coordination intervention with pre-post analysis of health care utilization. We enrolled Medicaid fee-for-service patients aged 18-64 who were admitted to an urban public hospital and identified as being at high risk for hospital readmission by a validated predictive algorithm. Enrolled patients were evaluated using qualitative and quantitative interview techniques to identify needs such as transportation to/advocacy during medical appointments, mental health/substance use treatment, and home visits. A community housing partner initiated housing applications in-hospital for homeless patients. Care managers facilitated appropriate discharge plans then worked closely with patients in the community using a harm reduction approach.</p> <p>Results</p> <p>Nineteen patients were enrolled; all were male, 18/19 were substance users, and 17/19 were homeless. Patients had a total of 64 inpatient admissions in the 12 months before the intervention, versus 40 in the following 12 months, a 37.5% reduction. Most patients (73.3%) had fewer inpatient admissions in the year after the intervention compared to the prior year. Overall ED visits also decreased after study enrollment, while outpatient clinic visits increased. Yearly study hospital Medicaid reimbursements fell an average of $16,383 per patient.</p> <p>Conclusions</p> <p>A pilot intervention for high-cost patients shows promising results for health services usage. We are currently expanding our model to serve more patients at additional hospitals to see if the pilot's success can be replicated.</p> <p>Trial registration</p> <p>Clinicaltrials.gov Identifier: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1292096">NCT01292096</a></p

Design as a provocation to support discussion about euthanasia: The Plug

Design as a provocation to support discussion about euthanasia: The Plu

Preventable hospitalization and access to primary health care in an area of Southern Italy

<p>Abstract</p> <p>Background</p> <p>Ambulatory care-sensitive conditions (ACSC), such as hypertension, diabetes, chronic heart failure, chronic obstructive pulmonary disease and asthma, are conditions that can be managed with timely and effective outpatient care reducing the need of hospitalization. Avoidable hospitalizations for ACSC have been used to assess access, quality and performance of the primary care delivery system. The aims of this study were to quantify the proportion of avoidable hospital admissions for ACSCs, to identify the related patient's socio-demographic profile and health conditions, to assess the relationship between the primary care access characteristics and preventable hospitalizations, and the usefulness of avoidable hospitalizations for ACSCs to monitor the effectiveness of primary health care.</p> <p>Methods</p> <p>A random sample of 520 medical records of patients admitted to medical wards (Cardiology, Internal Medicine, Pneumology, Geriatrics) of a non-teaching acute care 717-bed hospital located in Catanzaro (Italy) were reviewed.</p> <p>Results</p> <p>A total of 31.5% of the hospitalizations in the sample were judged to be preventable. Of these, 40% were for congestive heart failure, 23.2% for chronic obstructive pulmonary disease, 13.5% for angina without procedure, 8.4% for hypertension, and 7.1% for bacterial pneumonia. Preventable hospitalizations were significantly associated to age and sex since they were higher in older patients and in males. The proportion of patients who had a preventable hospitalization significantly increased with regard to the number of hospital admissions in the previous year and to the number of patients for each primary care physician (PCP), with lower number of PCP accesses and PCP medical visits in the previous year, with less satisfaction about PCP health services, and, finally, with worse self-reported health status and shorter length of hospital stay.</p> <p>Conclusion</p> <p>The findings from this study add to the evidence and the urgency of developing and implementing effective interventions to improve delivery of health care at the community level and provided support to the usefulness of avoidable hospitalizations for ACSCs to monitor this process.</p

Compliance with continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea among privately paying patients- a cross sectional study

Background: To evaluate the compliance, benefits and side effects associated with continuous positive airway pressure (CPAP) therapy among Pakistani patients treated for obstructive sleep apnea (OSA) in private sector.Methods: Patients diagnosed to have OSA based on overnight study who were recommended for CPAP therapy, between 1998 and 2003, were evaluated by telephonic survey and review of hospital notes. Compliance, benefits and side effects associated with CPAP therapy were assessed.Results: Out of 135 patients who were prescribed CPAP therapy, 75 could be contacted. Sixty (80%) started using CPAP within one month of diagnosis and 46 (61%) continued to use it long-term (beyond one year). Compliance with CPAP therapy was associated with higher body mass index, higher Epworth sleepiness scale score, history of witnessed apnea, and reduction in daytime sleepiness with CPAP therapy. OSA severity as assessed by apnea-hypopnea index did not affect compliance with CPAP therapy. Use of anti-depressants and CPAP induced sleep disturbances were associated with poor compliance with CPAP therapy.CONCLUSIONS: Obesity, excessive daytime sleepiness, witnessed apnea and improvement of daytime symptoms following use of CPAP were predictors of improved compliance. Use of antidepressants and CPAP induced sleep disturbances were predictors of poor compliance

Effects of climate and snow depth on Bromus tectorum population dynamics at high elevation

Invasive plants are thought to be especially capable of range shifts or expansion in response to climate change due to high dispersal and colonization abilities. Although highly invasive throughout the Intermountain West, the presence and impact of the grass Bromus tectorum has been limited at higher elevations in the eastern Sierra Nevada, potentially due to extreme wintertime conditions. However, climate models project an upward elevational shift of climate regimes in the Sierra Nevada that could favor B. tectorum expansion. This research specifically examined the effects of experimental snow depth manipulations and interannual climate variability over 5 years on B. tectorum populations at high elevation (2,175 m). Experimentally-increased snow depth had an effect on phenology and biomass, but no effect on individual fecundity. Instead an experimentally-increased snowpack inhibited population growth in 1 year by reducing seedling emergence and early survival. A similar negative effect of increased snow was observed 2 years later. However, a strong negative effect on B. tectorum was also associated with a naturally low-snow winter, when seedling emergence was reduced by 86%. Across 5 years, winters with greater snow cover and a slower accumulation of degree-days coincided with higher B. tectorum seedling density and population growth. Thus, we observed negative effects associated with both experimentally-increased and naturally-decreased snowpacks. It is likely that the effect of snow at high elevation is nonlinear and differs from lower elevations where wintertime germination can be favorable. Additionally, we observed a doubling of population size in 1 year, which is alarming at this elevation

In-reach specialist nursing teams for residential care homes : uptake of services, impact on care provision and cost-effectiveness

Background: A joint NHS-Local Authority initiative in England designed to provide a dedicated nursing and physiotherapy in-reach team (IRT) to four residential care homes has been evaluated.The IRT supported 131 residents and maintained 15 'virtual' beds for specialist nursing in these care homes. Methods: Data captured prospectively (July 2005 to June 2007) included: numbers of referrals; reason for referral; outcome (e.g. admission to IRT bed, short-term IRT support); length of stay in IRT; prevented hospital admissions; early hospital discharges; avoided nursing home transfers; and detection of unrecognised illnesses. An economic analysis was undertaken. Results: 733 referrals were made during the 2 years (range 0.5 to 13.0 per resident per annum)resulting in a total of 6,528 visits. Two thirds of referrals aimed at maintaining the resident's independence in the care home. According to expert panel assessment, 197 hospital admissions were averted over the period; 20 early discharges facilitated; and 28 resident transfers to a nursing home prevented. Detection of previously unrecognised illnesses accounted for a high number of visits. Investment in IRT equalled £44.38 per resident per week. Savings through reduced hospital admissions, early discharges, delayed transfers to nursing homes, and identification of previously unrecognised illnesses are conservatively estimated to produce a final reduction in care cost of £6.33 per resident per week. A sensitivity analysis indicates this figure might range from a weekly overall saving of £36.90 per resident to a 'worst case' estimate of £2.70 extra expenditure per resident per week. Evaluation early in implementation may underestimate some cost-saving activities and greater savings may emerge over a longer time period. Similarly, IRT costs may reduce over time due to the potential for refinement of team without major loss in effectiveness. Conclusion: Introduction of a specialist nursing in-reach team for residential homes is at least cost neutral and, in all probability, cost saving. Further benefits include development of new skills in the care home workforce and enhanced quality of care. Residents are enabled to stay in familiar surroundings rather than unnecessarily spending time in hospital or being transferred to a higher dependency nursing home setting

Environmental and vegetation controls on the spatial variability of CH4 emission from wet-sedge and tussock tundra ecosystems in the Arctic

Aims Despite multiple studies investigating the environmental controls on CH4 fluxes from arctic tundra ecosystems, the high spatial variability of CH4 emissions is not fully understood. This makes the upscaling of CH4 fluxes from plot to regional scale, particularly challenging. The goal of this study is to refine our knowledge of the spatial variability and controls on CH4 emission from tundra ecosystems. Methods CH4 fluxes were measured in four sites across a variety of wet-sedge and tussock tundra ecosystems in Alaska using chambers and a Los Gatos CO2 and CH4 gas analyser. Results All sites were found to be sources of CH4, with northern sites (in Barrow) showing similar CH4 emission rates to the southernmost site (ca. 300 km south, Ivotuk). Gross primary productivity (GPP), water level and soil temperature were the most important environmental controls on CH4 emission. Greater vascular plant cover was linked with higher CH4 emission, but this increased emission with increased vascular plant cover was much higher (86 %) in the drier sites, than the wettest sites (30 %), suggesting that transport and/or substrate availability were crucial limiting factors for CH4 emission in these tundra ecosystems. Conclusions Overall, this study provides an increased understanding of the fine scale spatial controls on CH4 flux, in particular the key role that plant cover and GPP play in enhancing CH4 emissions from tundra soils