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Biomedical subjects

L Loo

Publications and source records attributed to L Loo.

12 recordsLinked to original sources

Stroke disease management--a framework for comprehensive stroke care.

Disease management is an approach to patient care that coordinates medical resources for the patient across the entire healthcare delivery system throughout the lifetime of the patient with the disease. Stroke is suitable for disease management as it is a well-known disease with a high prevalence, high cost, variable practice pattern, poor clinical outcome, and managed by a non-integrated healthcare system. It has measurable and actionable outcomes, with available local expertise and support of the Ministry of Health. Developing the programme requires a multidisciplinary team, baseline data on target populations and healthcare services, identification of core components, collaboration with key stakeholders, development of evidence-based clinical practice guidelines and carepaths, institution of care coordinators, use of information technology and continuous quality improvement to produce an effective plan. Core components include public education, risk factor screening and management, primary care and specialist clinics, acute stroke units, inpatient and outpatient rehabilitation facilities, and supportive community services including medical, nursing, therapy, home help and support groups for patients and carers. The family physician plays a key role. Coordination of services is best done by a network of hospital and community-based care managers, and is enhanced by a coordinating call centre. Continuous quality improvement is required, with audit of processes and outcomes, facilitated by a disease registry. Pitfalls include inappropriate exclusion of deserving patients, misuse, loss of physician and patient independence, over-estimation of benefits, and care fragmentation. Collaboration and cooperative among all parties will help ensure a successful and sustainable programme.

Comprehensive Health Care↗

Solution structure of the interacting domains of the Mad-Sin3 complex: implications for recruitment of a chromatin-modifying complex.

Gene-specific targeting of the Sin3 corepressor complex by DNA-bound repressors is an important mechanism of gene silencing in eukaryotes. The Sin3 corepressor specifically associates with a diverse group of transcriptional repressors, including members of the Mad family, that play crucial roles in development. The NMR structure of the complex formed by the PAH2 domain of mammalian Sin3A with the transrepression domain (SID) of human Mad1 reveals that both domains undergo mutual folding transitions upon complex formation generating an unusual left-handed four-helix bundle structure and an amphipathic alpha helix, respectively. The SID helix is wedged within a deep hydrophobic pocket defined by two PAH2 helices. Structure-function analyses of the Mad-Sin3 complex provide a basis for understanding the underlying mechanism(s) that lead to gene silencing.

Amino Acid Sequence↗

Predicting non-elective hospital readmissions: a multi-site study. Department of Veterans Affairs Cooperative Study Group on Primary Care and Readmissions.

OBJECTIVE: To determine clinical and patient-centered factors predicting non-elective hospital readmissions. DESIGN: Secondary analysis from a randomized clinical trial. CLINICAL SETTING: Nine VA medical centers. PARTICIPANTS: Patients discharged from the medical service with diabetes mellitus, congestive heart failure, and/or chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASUREMENT: Non-elective readmission within 90 days. RESULTS: Of 1378 patients discharged, 23.3% were readmitted. After controlling for hospital and intervention status, risk of readmission was increased if the patient had more hospitalizations and emergency room visits in the prior 6 months, higher blood urea nitrogen, lower mental health function, a diagnosis of COPD, and increased satisfaction with access to emergency care assessed on the index hospitalization. CONCLUSIONS: Both clinical and patient-centered factors identifiable at discharge are related to non-elective readmission. These factors identify high-risk patients and provide guidance for future interventions. The relationship of patient satisfaction measures to readmission deserves further study.

Diabetes Mellitus↗

Classifying general medicine readmissions. Are they preventable? Veterans Affairs Cooperative Studies in Health Services Group on Primary Care and Hospital Readmissions.

OBJECTIVES: To describe a new quality assessment method used to classify the preventability of hospitalization in terms of patient, clinician, or system factors. DESIGN: The instrument was developed in two phases. Phase 1 was a prospective comparison of admitting residents' and their attending physicians' classifications of the perceived preventability of consecutive admissions to one Veterans Affairs Medical Center (VAMC) excluding admissions to the intensive care unit (ICU). In phase 2, a panel of 10 physicians rated 811 abstracted records of readmissions from nine VAMCs. SETTING: Nine VAMCs across the United States with varying degrees of university hospital affiliation. PATIENTS: Phase 1, 156 patients admitted to the general medicine service at the Durham VAMC. Phase 2, 514 patients accounting for 811 readmissions within 6 months of a general medicine service discharge at nine VAMCs. MEASUREMENTS AND MAIN RESULTS: Physicians used a checklist to record the reason for hospitalization, the preventability of the hospitalization, and, if preventable, a reason defining preventability, which was classified in terms of system, clinician, and patient factors. In phase 2, two physician panelists assessed preventability for each chart. When two panelists disagreed on the preventability of hospitalization, a third panelist, blind to the original assessments, rated the chart. In phase 1, residents and attending physicians rated 33% and 34% of admissions as preventable (kappa = 0.41), respectively. In phase 2, 277 (34%) of 811 readmissions were deemed preventable. Intraobserver accuracy for the assessment of preventability was 96% (kappa = 0.89). interobserver accuracy was 73% (kappa = 0.43). Hospital system factors accounted for 37% of preventable readmissions, clinician factors for 38%, and patient factors for 21%. The nine hospitals differed markedly in their profile of reasons for preventable readmissions (p = .005). CONCLUSIONS: Using a new method of determining the preventability of hospitalizations, we identified several factors that might avert hospitalizations. Focusing efforts to identify preventable hospitalizations may yield better methods for managing patients' total health care needs; however, the content of those efforts will vary by institution.

Adult↗

Induction of cytokines in normal placental cells by the human immunodeficiency virus.

Placental cotyledon mononuclear cells (CMC) resemble peripheral blood monocytes/marcophages (MM) with respect to their expression of surface antigens and cellular function. CMC also express the CD4 antigen receptor and are thus susceptible to infection with the human immunodeficiency virus (HIV). When vertical transmission of HIV from mother to fetus occurs, the infection often remains latent until appropriate factors initiate the transcription of virus-specific mRNA. Cytokines, such as interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) which are produced by MM, up-regulate HIV expression in infected cells. The induction of cytokines in MM does not require active infection with HIV since heat-inactivated HIV (iHIV) and envelope gp120 caused cytokine secretion. We studied the ability of CMC from normal placentas to secrete these cytokines following stimulation with endotoxin, iHIV, recombinant GP160 and GAG55, and synthetic p17, HGP-30. Whereas CMC spontaneously secreted low levels of IL-1 beta and TNF-alpha, they constitutively secreted high levels of IL-6. All cytokine levels could be boosted by endotoxin. GP160, iHIV, and HGP-30 failed to augment cytokine levels above baseline. In contrast, GAG55 significantly boosted only TNF-alpha. The relevance of these findings is discussed with respect to the putative roles of cytokines in the immunoregulation of HIV in utero.

Cell Transformation, Viral↗

Human carboxypeptidase E. Isolation and characterization of the cDNA, sequence conservation, expression and processing in vitro.

Carboxypeptidase E (CPE), which cleaves C-terminal amino acid residues and is involved in neuropeptide processing, is itself subject to intracellular processing. Human CPE cDNA was isolated and sequence comparisons were made with those of a previously isolated brain cDNA (M1622) encoding rat CPE and of other human carboxypeptidases (M and N). Human (2.5 kb) and rat (2.1 kb) CPE cDNAs approximated to the size of their respective mRNAs; additional sequences were located in putative 5' and 3' untranslated regions of human CPE mRNA. There is 79% sequence similarity between human and rat CPE cDNAs, with greater similarity (89%) over the coding region and short sections of the non-coding sequence. The predicted 476-amino acid-residue sequences of human and rat preproCPEs are highly conserved (96% identity), with lower degree of similarity of the N-terminal signal peptide (76%). Human CPE showed 51% and 43% sequence similarity to human CPN and CPM respectively, with discrete regions of divergence dispersed between the highly conserved mechanistically implicated regions. Antiserum generated from a fusion protein, synthesized in Escherichia coli from constructs of the human cDNA, recognized an approx. 50 kDa membrane protein and a smaller soluble protein in rat and human brain preparations, corresponding to the two forms of native CPE. Human CPE mRNA transcripts directed the synthesis in reticulocyte lysate of a 54 kDa translation product, which in the presence of dog pancreas microsomal membranes was co-translationally processed with cleavage, insertion into membranes and glycosylation. Three processed forms were generated, the largest (56 kDa) and smallest (52 kDa) being equally glycosylated. The membrane association of the processed translation products and of native brain membrane CPE, detected immunologically, was resistant to moderate alkali but not pH 11.5 extraction. These results are consistent with secondary-structure predictions that CPE is a peripheral membrane protein. The dissimilar regions of human carboxypeptidases may provide information on sequences responsible for their different cellular disposition.

Amino Acid Sequence↗