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Biomedical subjects

J Rasmussen

Publications and source records attributed to J Rasmussen.

At least 19 recordsLinked to original sources
PubMed2005

"Going solid": a model of system dynamics and consequences for patient safety.

Rather than being a static property of hospitals and other healthcare facilities, safety is dynamic and often on short time scales. In the past most healthcare delivery systems were loosely coupled-that is, activities and conditions in one part of the system had only limited effect on those elsewhere. Loose coupling allowed the system to buffer many conditions such as short term surges in demand. Modern management techniques and information systems have allowed facilities to reduce inefficiencies in operation. One side effect is the loss of buffers that previously accommodated demand surges. As a result, situations occur in which activities in one area of the hospital become critically dependent on seemingly insignificant events in seemingly distant areas. This tight coupling condition is called "going solid". Rasmussen's dynamic model of risk and safety can be used to formulate a model of patient safety dynamics that includes "going solid" and its consequences. Because the model addresses the dynamic aspects of safety, it is particularly suited to understanding current conditions in modern healthcare delivery and the way these conditions may lead to accidents.

Efficiency, Organizational↗
PubMed2004

Genetic characterization of orf viruses isolated from various ruminant species of a zoo.

In the present study, an outbreak of proliferative dermatitis in musk ox (Ovibos moschatus), Sichuan takin (Budorcas taxicolor tibetana) and domestic Shetland sheep (Ovis aries) in a zoo is described. Skin lesions consisted of severe, persistent, multifocal, proliferative dermatitis in musk ox, and mild, transient, focal, dermatitis in the Sichuan takin and Shetland sheep. Parapoxviruses were isolated from skin lesions, and characterized by restriction enzyme analysis and partial gene sequencing. The results of this investigation indicate that the outbreak of proliferative dermatitis was due to infection by a single parapoxvirus, which is genetically closely related to other orf virus (ORFV) strains but distant to bovine papular stomatitis virus (BPSV) and pseudocowpox virus (PCPV).

Amino Acid Sequence↗
PubMed2003

The role of error in organizing behaviour. 1990.

During recent years the significance of the concept of human error has changed considerably. The reason for this has partly been an increasing interest of psychological research in the analysis of complex real life phenomena, and partly the changes of modern work conditions caused by advanced information technology. Consequently, the topic of the present contribution is not a definition of the concept or a proper taxonomy. Instead, a review is given of two professional contexts for which the concept of error is important. Three cases of analysis of human-system interaction are reviewed: (1). traditional task analysis and human reliability estimation; (2). causal analysis of accidents after the fact, and (3). design of reliable work conditions in modern sociotechnical systems. It is concluded that "errors" cannot be studied as a separate category of behaviour fragments; the object of study should be cognitive control of behaviour in complex environments.

Efficiency, Organizational↗
PubMed2001

The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis.

Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddI/d4T decreased the numbers of infected cells by 75%, while ddI/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by > or = 25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.

Animals↗
PubMed2001

Reduction in glial immunity and neuropathology by a PAF antagonist and an MMP and TNFalpha inhibitor in SCID mice with HIV-1 encephalitis.

The effects of anti-inflammatory drugs on glial immunity and neuropathology were determined in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis. HIV-1-infected human monocyte-derived macrophages (MDM) are stereotactically inoculated into basal ganglia resulting in a multinucleated giant cell encephalitis. A platelet activating factor antagonist and a matrix metalloproteinase inhibitor, which also inhibits tumor necrosis factor alpha release, were administered to animals at the time of the MDM inoculation. The drugs administered in combination markedly reduced brain inflammation, astrogliosis and microglia activation. These findings demonstrate that reduction of brain inflammatory responses, independent of viral replication, can affect HIVE pathology in an animal model system of disease.

AIDS Dementia Complex↗
PubMed2001

Muscle recruitment by the min/max criterion -- a comparative numerical study.

This paper introduces the min/max criterion for simulation of muscle recruitment in multiple muscle systems. The criterion is introduced and justified by comparison to two known criterion types: the polynomial criterion and the soft saturation criterion. The comparison is performed on a planar three-muscle elbow model performing a dumbbell curl. A generalized form of the soft saturation criterion is introduced, and it is shown that the min/max criterion can be interpreted as the limit of the classical criteria when the exponents in their mathematical expressions approach infinity. We finally show how the min/max criterion can be cast into a form that allows for efficient and robust numerical solution by linear programming. It is concluded that the min/max criterion possesses a number of attractive physiological as well as algorithmic advantages.

Algorithms↗
PubMed2000

Evaluation of antiretroviral drug efficacy for HIV-1 encephalitis in SCID mice.

OBJECTIVES: To compare the efficacy of the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir, zidovudine (AZT), lamivudine (3TC), didanosine (ddI), and stavudine (d4T) to inhibit viral replication in brain macrophages. A severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE) was used to monitor spreading viral infection in the CNS. BACKGROUND: The development of antiretroviral therapies with CNS efficacy against neuroinvasive virus is important if eradication of HIV-1 can be achieved within critical "hidden reservoirs." METHODS: HIV-1-infected human monocyte-derived macrophages (MDMs) (after a single round of viral replication) were inoculated into the caudate and putamen of SCID mice. This resulted in the spreading of viral infection with a concomitant multinucleated giant cell encephalitis (astrogliosis, microglial activation, and neuronal injury). NRTIs were administered to animals at the time of intracerebral MDM inoculations and continued until the time of sacrifice. Antiretroviral effects were assessed by viral load and percentages of infected MDMs. RESULTS: In brains of SCID mice with HIVE, abacavir and lamivudine reduced HIV-1 p24 antigen-positive cells by 80% and 95%, respectively, whereas both decreased viral load by approximately 1 log. Zidovudine, didanosine, and stavudine showed variable effects. CONCLUSION: Abacavir and lamivudine showed significant antiretroviral activity in SCID mice with HIVE when compared with other NRTIs. The extrapolation of these results to humans with HIV-1 dementia awaits future investigations.

AIDS Dementia Complex↗
PubMed2000

Human factors in a dynamic information society: where are we heading?

Society is becoming increasingly dynamic and integrated owing to the extensive use of information technology. This has several implications that pose new challenges to the human factors profession. In an integrated society, changes and disturbances propagate rapidly and widely and the increasing scale of operations requires also that rare events and circumstances are considered during systems design. In this situation, human factors contributions should be increasingly proactive, not only responding to observed problems, but also, they should be based on models of adaptive human behaviour in complex, dynamic systems. The paper suggests some methodological issues to consider for human factors analyses by designers, evaluators and teachers.

Computer Systems↗
PubMed1999

Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis.

The numbers of immune-activated brain mononuclear phagocytes (MPs) affect the progression of human immunodeficiency virus (HIV)-1-associated dementia (HAD). Such MPs originate, in measure, from a pool of circulating monocytes. To address the mechanism(s) for monocyte penetration across the blood-brain barrier (BBB), we performed cross-validating laboratory, animal model, and human brain tissue investigations into HAD pathogenesis. First, an artificial BBB was constructed in which human brain microvascular endothelial and glial cells-astrocytes, microglia, and/or monocyte-derived macrophages (MDM)-were placed on opposite sides of a matrix-coated porous membrane. Second, a SCID mouse model of HIV-1 encephalitis (HIVE) was used to determine in vivo monocyte blood-to-brain migration. Third, immunohistochemical analyses of human HIVE tissue defined the relationships between astrogliosis, activation of microglia, virus infection, monocyte brain infiltration, and beta-chemokine expression. The results, taken together, showed that HIV-1-infected microglia increased monocyte migration through an artificial BBB 2 to 3.5 times more than replicate numbers of MDM. In the HIVE SCID mice, a marked accumulation of murine MDM was found in areas surrounding virus-infected human microglia but not MDM. For human HIVE, microglial activation and virus infection correlated with astrogliosis, monocyte transendothelial migration, and beta-chemokine expression. Pure cultures of virus-infected and activated microglia or astrocytes exposed to microglial conditioned media produced significant quantities of beta-chemokines. We conclude that microglial activation alone and/or through its interactions with astrocytes induces beta-chemokine-mediated monocyte migration in HAD.

AIDS Dementia Complex↗
PubMed1997

Outcome of nursing home care for residents with alcohol use disorders.

OBJECTIVES: To describe the outcome of nursing home (NH) care for a previously established cohort of residents with active, inactive or no alcohol use disorder (AUD), and to examine demographic variables, health services utilization, mortality and drinking behaviors in this group. DESIGN: Retrospective cohort study with participant interviews at NH admission and 3 years later. SETTING: Urban Veterans Affairs (VA) Medical Center and Nursing Home Care Unit (NHCU). PARTICIPANTS: Patients older than age 50 admitted consecutively to a VA NHCU between July 1991 and February 1993 who completed a structured interview, N = 117. MAIN OUTCOME MEASURES: AUD as determined by DSM-III-R criteria. Demographics, health services utilization and mortality as abstracted from the VA medical record. RESULTS: Health service utilization as measured by care episodes was not significantly different in the three groups (active, inactive and no AUD), but subjects with AUD had documented health services use related to alcoholism, including hospitalizations for alcohol-related illness, placements in long-term care facilities to control drinking and death from alcohol-related causes. The mean age at death was significantly younger for study participants with active or inactive AUD compared to those with no AUD: 67.7, 70.4 and 77.9 years, respectively (p < 0.004). Of the 21 participants with active AUD at NHCU entry, 11 resumed drinking after discharge and six still met criteria for active AUD 3 years later. CONCLUSIONS: The subset of NHCU patients with active AUD continued to incur alcohol-related hospitalizations and institutionalizations following NHCU discharge and suffered early mortality relative to their peers. Effective models of care for this subset of patients should be sought.

Age Factors↗
PubMed1996

Agonist-induced functional desensitization of the mu-opioid receptor is mediated by loss of membrane receptors rather than uncoupling from G protein.

The effects of acute exposure of the opioid peptide [D-Ala2,N-MePhe4, Gly-ol5]enkephalin (DAMGO) on the mu-opioid receptor were examined in Chinese hamster ovary (CHO) K-1 and baby hamster kidney stable transfectants. In the CHO cell line, acute 1-hr treatment with DAMGO decreased the density of receptors without affecting the affinity or proportion of agonist-detected sites and attenuated the ability of the agonist to inhibit forskolin-stimulated cAMP accumulation. In contrast, similar 1-hr treatment of baby hamster kidney cells did not affect receptor density or agonist ability to inhibit cAMP accumulation, but longer duration of agonist exposure resulted in a reduction in membrane receptor, identical to the CHO cells. These results suggested that for the mu-opioid receptor, alteration in receptor density was the major determinant for the observed agonist-induced desensitization. Consistent with this notion, the ratio of the DAMGO concentration yielding half-maximal occupation of the mu receptor to that yielding half-maximal functional response was < 1. This suggests the necessity for a high mu receptor occupancy rate for maximal functional response, so that any loss of cell surface opioid-binding sites was a critical determinant in reducing the maximal response. This hypothesis was further supported by the observation that irreversible inactivation of fixed proportions of opioid-binding sites with beta-chlorn-altrexamine demonstrated that there were few spare receptors, which is in contrast to what has been reported for other G protein-coupled receptors, including the delta-opioid receptor. Taken together, these data suggest that the opioid agonist DAMGO has a high affinity for the mu receptor but must occupy > 70% of the available receptors to generate the maximal second messenger-linked response.

Analgesics↗