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1.  The Rapid Assessment Interface and Discharge service and its implications for patients with dementia 
The rising prevalence of dementia will have an effect on acute care hospitals around the world. At present, around 40% of patients older than 70 years with acute medical admissions have dementia, but only half of these patients have been diagnosed. Patients with dementia have poorer health outcomes, longer hospital stays, and higher rates of readmissions and institutionalization. Worldwide, health care budgets are severely constrained. National Institute for Health and Care Excellence (NICE) has listed ten quality standards for supporting people in living well with dementia. NICE resource implications and commissioning support to implement these guidelines and improve dementia services have been recently published. Although most of the frail elderly patients with dementia are cared for by geriatricians, obstacles to making a diagnosis and to the management of dementia have been recognized. To provide a timely diagnosis of dementia, better care in acute hospital settings, and continuity of care in the community, services integrating all these elements are warranted. Extra resources also will be required for intermediate, palliative care, and mental health liaison services for people with dementia. The Birmingham Rapid Assessment Interface and Discharge service model uses a multiskilled team that provides comprehensive assessment of a person’s physical and psychological well-being in a general hospital setting. It has been shown to be an effective model in terms of reducing both length of stay and avoiding readmission. The aim of this review is to discuss the implications of the Rapid Assessment Interface and Discharge model in people with dementia and to critically compare this model with similar published service provisions.
PMCID: PMC3754487  PMID: 23986633
comorbidity; aged; hospitals; dementia; cost
2.  Cryptosporidiosis in Rhesus Macaques Challenged During Acute and Chronic Phases of SIV Infection 
The intestinal immune dysfunction due to loss of mucosal and peripheral CD4+ T cells in individuals with HIV/AIDS is presumably responsible for the establishment of persistent cryptosporidiosis. Simian immunodeficiency virus (SIV)-infected macaques were used to investigate the phase/timing in SIV infection, which permits a self-limiting Cryptosporidium parvum infection to become persistent in immunodeficient hosts because of significant mucosal immune defects. Two groups of SIV-infected macaques were challenged with C. parvum; one was challenged during the acute SIV infection phase (2 weeks post-SIV infection) and the second was challenged during the chronic SIV phase (CD4 counts 200–500 cells/μl of blood). Samples (fecal, blood, biopsy, and necropsy) were collected at different time points after infection to correlate the progression of disease with the immune status of the animals. All seven SIV-infected macaques challenged during the acute phase of SIV infection became persistently infected and excreted oocysts for 1–4 months. However, four of the six in the chronic SIV phase became infected with cryptosporidiosis, of which one survived 2 weeks and one became naturally infected. Sequential analysis of CD4+ in blood and intestines of coinfected macaques exhibited pronounced losses of CD4 T cells during the first 2 weeks after SIV infection, followed by transient rebound of CD4 T cells in the gut after C. parvum infection, and then a gradual loss over subsequent months. Persistent cryptosporidiosis was more consistently induced during the acute SIV phase indicating that profound viral damage to gut lymphoid tissue during the acute phase was more conducive, compared with the chronic phase, to establishing persistent cryptosporidiosis than low circulating CD4 T cells.
PMCID: PMC3161110  PMID: 21314434
3.  Serial Propagation of the Microsporidian Enterocytozoon bieneusi of Human Origin in Immunocompromised Rodents  
Infection and Immunity  2006;74(8):4424-4429.
Enterocytozoon bieneusi, a microsporidian, is clinically one of the most significant opportunistic causes of diarrhea and wasting associated with profound human immunodeficiencies. The lack of an animal model for E. bieneusi hinders serious investigations and limits the availability of spores to individuals with severe human immunodeficiency virus/AIDS disease who are infected with E. bieneusi. The development of procedures for purification and concentration of spores from stools of infected humans has led to the production of immune reagents and provided a source of spores to conduct research, including attempts to develop and serially propagate E. bieneusi in rodent models. We have evaluated and successfully infected six different immunodeficient and/or immunosuppressed rodent models and have demonstrated persistent infections lasting at least 18 weeks in SCID mice and in nude rats. To enhance the intensity and duration of infection in these two models, animals were given anti-gamma interferon monoclonal antibody injections at regular intervals. Of the six models evaluated, nude rats and gerbils immunosuppressed with dexamethasone excreted the highest number of spores and for longer time periods. Four different E. bieneusi isolates were equally infectious, and one of them was serially propagated in nude rats six times over a period of 10 months. Typically, rats challenged orally with 104 spores yielded 2 × 107 to 6.3 × 107 spores per single fecal sample when the level of spores was measured 2 weeks later. Rodent models and a nonhuman source of fresh spores will considerably enhance future investigations on this important opportunistic pathogen, including the screening and evaluation of urgently needed chemotherapeutic agents.
PMCID: PMC1539595  PMID: 16861628
4.  Immune Response to Individual Maedi-Visna Virus gag Antigens 
Journal of Virology  2006;80(2):912-919.
The lesions caused by maedi-visna virus (MVV) are known to be immune mediated with a presumed contribution by the response to viral antigens. However, very little is known about the T-cell response to individual viral proteins. We have therefore expressed the three individual gag antigens of MVV strain EV1 (p16, p25, and p14) in a bacterial expression system and used the purified recombinant proteins to analyze the antibody and CD4+ T-cell response to MVV. Plasma samples were taken from sheep after 1 year of infection with MVV. The titers for antibodies in these samples were determined by indirect enzyme-linked immunosorbent assays and were as follows: anti-p25 antibody, 1:400 to >1:3,200; anti-p16 antibody, 1:400 to 1:3,200; and anti-p14 antibody, 1:<100 to 1:3,200. When the induction of antibodies was followed over time postinfection (p.i.), samples positive for anti-p25 were seen by day 24 p.i., followed by anti-p16 by day 45 p.i., and lastly anti-p14 by day 100 p.i. T-cell proliferative responses to all three gag antigens were detected in persistently infected sheep peripheral blood lymphocytes. The antigens were therefore used to raise T-cell lines from persistently infected sheep. These T-cell lines were shown to be specific for the recombinant gag antigens and for viral antigen expressed on infected macrophages. The proliferative response was restricted to major histocompatibility complex class II HLA-DR and so was due to CD4+ T lymphocytes. All three gag antigens may therefore play a role in immune-mediated lesion formation in MVV disease by presentation on infected macrophages in lesions.
PMCID: PMC1346880  PMID: 16378993
5.  Sensitivity and Specificity of a Monoclonal Antibody-Based Fluorescence Assay for Detecting Enterocytozoon bieneusi Spores in Feces of Simian Immunodeficiency Virus-Infected Macaques 
Enterocytozoon bieneusi is clinically the most significant among the microsporidia causing chronic diarrhea, wasting, and cholangitis in individuals with human immunodeficiency virus/AIDS. Microscopy with either calcofluor or modified trichrome stains is the standard diagnostic test for microsporidiosis and does not allow species identification. Detection of E. bieneusi infection based on PCR is limited to a few reference laboratories, and thus it is not the standard diagnostic assay. We have recently reported the development and characterization of a panel of monoclonal antibodies against E. bieneusi, and in this publication we evaluated the specificity and sensitivity of an immunofluorescence assay (IFA), compared with PCR, in simian immunodeficiency virus-infected macaques. The IFA, which correlated with the primary PCR method, with a detection limit of 1.5 ×105 spores per gram of feces, will simplify considerably the detection of E. bieneusi spores in clinical and environmental specimens and in laboratory and epidemiological investigations.
PMCID: PMC1247839  PMID: 16210474
6.  Monoclonal Antibodies against Enterocytozoon bieneusi of Human Origin 
Enterocytozoon bieneusi is clinically the most significant among the microsporidia infecting humans, causing chronic diarrhea, wasting, and cholangitis in individuals with human immunodeficiency virus/AIDS. The lack of immune reagents is largely due to the absence of methods for laboratory propagation of E. bieneusi. We recently described a procedure for the concentration and purification of spores from diarrheic stool of infected humans. Purified spores were used to immunize mice for production and screening of monoclonal antibodies (MAbs) against E. bieneusi. The eight immunoglobulin M MAbs generated and fully characterized did not cross-react with other human microsporidia or with other microorganisms normally present in stool. One of the MAbs, 2G4, reacted with E. bieneusi spores in stools from monkeys and humans, without background fluorescence, which makes it an ideal diagnostic reagent. It also recognizes intracellular stages of the parasite and will be suitable for determining tissue distribution of E. bieneusi in infected hosts. At least two immunodominant antigens of E. bieneusi of 33,000 and 35,000 Da exist, which were recognized by rabbit and mouse antisera. The availability of MAbs against E. bieneusi will simplify considerably the diagnosis of this infection in humans and will provide tools for epidemiologic investigations regarding the true prevalence of the infection in various human and mammalian populations and the environmental sources of infection.
PMCID: PMC1235791  PMID: 16148179
7.  Production and Characterization of Monoclonal Antibodies against Enterocytozoon bieneusi Purified from Rhesus Macaques  
Infection and Immunity  2005;73(8):5166-5172.
Enterocytozoon bieneusi spores derived from rhesus macaque feces were purified by serial salt-Percoll-sucrose-iodixanol centrifugation, resulting in two bands with different specific densities of 95.6% and 99.5% purity and with a recovery efficiency of 10.8%. An ultrastructural examination revealed typical E. bieneusi spores. Twenty-six stable hybridomas were derived from BALB/c mice immunized with spores and were cloned twice by limiting dilution or growth on semisolid medium. Four monoclonal antibodies (MAbs), reacting exclusively with spores, were further characterized. These MAbs specifically reacted with spores present in stools of humans and macaques, as visualized by immunofluorescence, and with spore walls, as visualized by immunoelectron microscopy. A blocking enzyme-linked immunosorbent assay and Western blotting revealed that the epitope recognized by 8E2 was different from those recognized by 7G2, 7H2, and 12G8, which identified the same 40-kDa protein. These MAbs will be valuable tools for diagnostics, for epidemiological investigations, for host-pathogen interaction studies, and for comparative genomics and proteomics.
PMCID: PMC1201209  PMID: 16041034
8.  Recombinant Proteins of Cryptosporidium parvum Induce Proliferation of Mesenteric Lymph Node Cells in Infected Mice  
Infection and Immunity  2005;73(8):5245-5248.
Recombinant antigens of Cryptosporidium parvum, Cp900 and Cp40 but not Cp15, stimulated C. parvum-specific proliferative immune responses of mesenteric lymph node cells in C57BL/6J mice infected with different isolates (MD, GCH1, UCP, and IOWA) of C. parvum, indicating that both Cp900 and Cp40 are immunodominant targets of cellular immune responses during C. parvum infection.
PMCID: PMC1201208  PMID: 16041049

Results 1-8 (8)