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Biomedical subjects

T A Larson

Publications and source records attributed to T A Larson.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of the impact and acceptance of a nutrition program in an HIV community clinic.

The present paper describes the evaluation of a nutrition service and research model for human immunodeficiency virus (HIV)-positive clients within a community based HIV acquired immune deficiency syndrome (AIDS) medical clinic. This program was designed to develop an effective, practical, replicable model for the delivery of nutrition services in the ambulatory HIV care setting. The objectives of evaluating the model were to define the ways that nutrition services in HIV/AIDS impacted clients, the clinic, and referral sources, and to continually refine the model by determining what services provide greatest benefit to clients, especially in view of the changing landscape of HIV therapy. Four evaluation activities completed during the study period of 5 years are described. These included a focus group and semistructured interview with clients, a semistructured interview with workers from the local network of service referral agencies and a client satisfaction survey at study "close-out." These evaluation processes confirmed or prompted programmatic modifications that improved access, confidentiality, and the relevance of specific components for clients. Providers/stakeholder's concerns were addressed through more frequent communication about clients' specific nutrition issues, clearer and easier referral and cooperation in recruiting patients. Also, the evaluation activities provided a platform for the communication of general and specific information about the program and for outreach. Although clients' and workers' priorities differed in some details of program implementation, there was strong agreement on the value of addressing nutrition concerns in HIV. Favorable feedback about the program gave impetus to continue nutrition services in the clinic after the project period ended and supports its application in other sites and settings.

Adult↗
PubMed2001

Finding the underserved: directions for HIV care in the future.

The demographic, behavior, and background characteristics of 4,804 participants in 17 national demonstration projects for HIV medical and/or psychosocial support services were coded for an index of "service need" or possible under-representation in the traditional healthcare system. Fifteen items were coded including status as a person of color, lack of private insurance, unemployment/disability, problem drinking, crack cocaine use, heroin use, other illicit drug use, less than 12 years of education, criminal justice system involvement, children requiring care while the patient receives services, sex work, being the sex partner of an injection drug user, unstable housing, primary language not English, and age less than 21 or over 55 years. Most (87.7%) of the program participants had four or more of these factors present. Through CHAID modeling, those groups with the highest levels of service need and vulnerability were identified. These data suggest that these projects, designed to attract and serve individuals potentially underrepresented in the health services system, had in fact achieved that goal. Implications of the changing demographics of the HIV epidemic for the health service delivery system are discussed.

Adult↗
PubMed2000

Key elements for implementing comprehensive health care models for persons with HIV: a stakeholder analysis.

A semistructured interview was conducted with 69 stakeholders in three university-based health care projects that were funded to provide an integrated continuum of care for persons living with HIV/AIDS. Data from the key informant interviews yielded composite indicators of familiarity with the service model, the importance of the elements in the service model, and the perceived quality of services provided by these innovative HIV service demonstration projects. Ratings of service quality were related to ratings of the respondent's knowledge of the service demonstration project, the importance of the various elements in the service continuum, and several indicators of stakeholder characteristics using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). The groups of stakeholders most likely to give the highest quality or success ratings for these projects are identified. The implications of these findings for developing collaborative and comprehensive service models for persons with HIV/AIDS are discussed.

Comprehensive Health Care↗
PubMed2000

Typology of quality of life experiences among persons living with HIV.

This article develops a typology of 2,038 participants in 13 innovative HIV/AIDS treatment model service demonstration projects targeted to traditionally underserved populations. The typology is based on self-reported health-related quality of life levels. Eight clusters were identified that classify HIV/AIDS patients based on their reported health-related quality of life. Participants were clustered based on their overall levels of quality of life, as well as by deficits in specific areas of functioning such as energy level, physical impairment, and role impairment. However, factor analysis suggests that health-related quality of life as perceived by the HIV-positive participants is best represented as a single underlying dimension and an ordering of the types shows that they are consistently related, in the same order, to several criterion measures of impairment. The results suggest that a general categorization of patients with HIV in terms of quality of life is more meaningful than an assessment of the relative areas of impairment. Since the impairment ratings were also self-reported, analyses relating quality of life clusters to actual symptom levels and healthcare utilization are needed. Implications for the assessment of health-related quality of life and the evaluation of service delivery programs for persons living with HIV are discussed.

Adult↗
PubMed2000

Service needs and factors related to quality of life at time of service enrollment among persons living with HIV.

This article explores the relationships of HIV risk factors, service needs, and vulnerabilities to health-related quality of life in a sample of 1,371 participants newly enrolled into 13 innovative HIV/AIDS treatment model service demonstration projects. These projects targeted services to traditionally underserved populations. Eight distinct quality of life clusters of HIV patients were used in this analysis along with patient self-identified risk factors. The quality of life clusters were based on patient self-reported quality of life dimensions. The eight clusters were differentiated based on relative strengths and weaknesses in physical functioning, energy levels, and social functioning. Data on patient need-vulnerability factors and demographic characteristics were related to these eight clusters using the data modeling method of Exhaustive CHAID (Chi-squared Automatic Interaction Detector). Through this method, the characteristics most likely to be associated with higher and lower levels of quality of life at the time of enrollment into services were identified. The results provide further support that quality of life assessment is a useful clinical tool for monitoring patient progress.

Adolescent↗
PubMed1998

Building comprehensive HIV/AIDS care services.

This article presents the experiences of three innovative programs for HIV/AIDS-related health care funded by the Health Resources and Services Administration (HRSA) Special Projects of National Significance (SPNS) Program. The Comprehensive Healthcare projects were funded as part of a larger initiative for innovative HIV service delivery models, consisting of 27 grantees, the funding agency (HRSA), and an Evaluation and Dissemination Center. These projects--the University of Nevada School of Medicine's Early Nutrition Intervention in HIV and AIDS project, the University of Vermont and State Agricultural College's Rural HIV Service Delivery project, and Washington University School of Medicine's Helena Hatch Special Care Center for Women--have developed specialized medical care models within the context of a continuum of services in a medical clinic. This article serves to describe the initial experiences of these three service demonstration projects, and some of the lessons learned as a result of their implementation. All of these projects share the goal of providing integrated services, such as medical care, nutrition, case management, and social and mental health services to people living with HIV/AIDS. However, the projects target different populations, (e.g., those in rural areas versus those in a large inner city), and use contrasting service delivery models of comprehensive HIV care. These projects have undertaken diverse activities and have used numerous effective strategies to increase their ability to provide a continuum of care and services for people living with HIV/AIDS. Based on the valuable lessons that the Comprehensive Healthcare projects learned during the first 2 years of funding, a number of collective recommendations have been made. It is expected that these suggestions will prove extremely useful to other programs that consider offering comprehensive health-care services to people living with HIV/AIDS or other complex medical conditions.

Academic Medical Centers↗
PubMed1996

An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes.

Homologous recombination in embryonal stem cells has been used to produce a fusion oncogene, thereby mimicking chromosomal translocations that frequently result in formation of tumor-specific fusion oncogenes in human malignancies. AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusion gene occurred from endogenous Mll transcription control elements, as in t(9;11) found in human leukemias. Chimeric mice carrying the fusion gene developed tumors, which were restricted to acute myeloid leukemias despite the widespread activity of the Mll promoter. Onset of perceptible disease was preceded by expansion of ES cell derivatives in peripheral blood. This novel use of homologous recombination formally proves that chromosomal translocations contribute to malignancy and provides a general strategy to create fusion oncogenes for studying their role in tumorigenesis.

Acute Disease↗
PubMed1996

Stability of epinephrine hydrochloride in an extemporaneously compounded topical anesthetic solution of lidocaine, racepinephrine, and tetracaine.

The stability of lidocaine, epinephrine (as racepinephrine, or racemic epinephrine), and tetracaine (LET) in a topical anesthetic solution under various conditions was studied. The LET solution was prepared by mixing together 100 mL of 20% lidocaine hydrochloride, 50 mL of 2.25% racepinephrine (as the hydrochloride salt), 125 mL of 2% tetracaine hydrochlorides 315 mg of sodium metabisulfite, and 225 mL of water. The solution was stored in three amber glass and two clear glass bottles. One amber container and one clear container were stored at 35 degrees C, one amber and one clear container were stored at room temperature (approximately 18 degrees C), and the third amber container was stored at 4 degrees C. Except for the refrigerated container, each bottle was subjected to continuous room light. Each of the five solutions was sampled at 0, 1, 2, 3, 4, 8, 16, and 26 weeks for visual inspection and high-performance liquid chromatography (HPLC). The HPLC assay was shown to be stability indicating for epinephrine only. All the drugs in the LET solution had no more than a 5% reduction from initial concentration, according to the assay, when stored for 4 weeks in amber or glass containers at 4 or 18 degrees C and when stored for 26 weeks in amber containers at 4 degrees C. Solution stored in clear containers discolored more quickly than solution stored in amber containers. Epinephrine in an extemporaneously prepared LET solution was stable in amber glass bottles for 4 weeks at 18 degrees C and for 26 weeks at 4 degrees C.

Anesthetics, Local↗
PubMed1996

Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice.

The LMO2 and TAL1 genes were first identified via chromosomal translocations and later found to encode proteins that interact during normal erythroid development. Some T cell leukaemia patients have chromosomal abnormalities involving both genes, implying that LMO2 and TAL1 act synergistically to promote tumorigenesis after their inappropriate co-expression. To test this hypothesis, transgenic mice were made which co-express Lmo2 and Tal1 genes in T cells. Dimers of Lmo2 and Tal1 proteins were formed in thymocytes of double but not single transgenic mice. Furthermore, thymuses of double transgenic mice were almost completely populated by immature T cells from birth, and these mice develop T cell tumours approximately 3 months earlier than those with only the Lmo2 transgene. Thus interaction between these two proteins can alter T cell development and potentiate tumorigenesis. The data also provide formal proof that TAL1 is an oncogene, apparently acting as a tumour promoter in this system.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice.

RBTN2 is activated by the chromosomal translocation t(11;14) (P13;p11) in some T cell leukaemias. Histologically similar T cell tumours develop with long latency in transgenic mice when either CD2 or thy1.1 promoters control rbtn2 expression. During the asymptomatic period, perturbation of T cell differentiation occurs in the thymus. The major anomalies present during this phase are an increase in the percentage of large thymocytes lacking CD4 and CD8 markers and also of small thymocytes express both the T cell marker CD3 and the B cell-specific form of CD45. These abnormal T cell populations can be clonal and thus a primary result of aberrant expression of the LIM-protein Rbtn2 is alteration of T cell differentiation preceding overt malignancy. These data provide a biological explanation for the role of Rbtn2 in tumorigenesis and presumably RBTN2 expression in T cells after the translocation t(11;14) in children has the same effect.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Indomethacin suppositories versus intravenously titrated morphine for the treatment of ureteral colic.

STUDY OBJECTIVES: To develop a protocol for the blinded IV titration of morphine and to compare the analgesic efficacy and side effect profile of indomethacin suppositories versus IV morphine in the treatment of acute ureteral colic. DESIGN: Randomized, double-blind, double-dummy, two-period crossover study. SETTING: Emergency department of a central-city, teaching hospital. PARTICIPANTS: Patients 18 to 75 years of age with pain suggestive of ureteral colic. Exclusions included pregnancy, adverse reactions to the study drugs, chronic nonsteroidal anti-inflammatory drug (NSAID) therapy, or any pain medicine taken within four hours of ED admission. INTERVENTIONS: Patients were randomized to one of two groups: indomethacin 100-mg rectal suppository or morphine by IV titration (5-mg loading dose and up to two additional 2.5-mg doses if needed). At the end of 30 minutes, if adequate pain relief had not been obtained, treatment was crossed over. MEASUREMENTS: Verbal analog scale (initial pain) and visual analog pain relief scale. MAIN RESULTS: Seventy-five patients were entered into the study. Only data from those patients with stone presence confirmed by IV pyelogram or stone passage were analyzed. Twenty-four could not be evaluated (23 who did not meet criteria for stone presence and one whose pain resolved spontaneously before study medications could be administered). Of the remaining 51 patients, 31 received indomethacin first and 20 received morphine first. Morphine recipients reported more pain relief at ten minutes (P = .02), but at 20 and 30 minutes, no significant difference (P = .17 and .74, respectively) existed between the two groups. CONCLUSION: IV morphine produced more rapid analgesia than rectally administered indomethacin. There were no significant differences in vital sign changes or number of side effects between the two treatment groups. This study is the first to compare an NSAID with morphine administered by IV titration, considered by many to be the "gold standard" for relief of acute, severe pain. Future studies could evaluate the simultaneous administration of an opioid combined with an NSAID or compare an IV titrated opioid with an IV NSAID.

Adult↗
PubMed1994

Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan.

Serum obtained from normal human subjects contains antibodies reactive in an enzyme-linked immunosorbent assay with the glucuronoxylomannan (GXM) of Cryptococcus neoformans. The frequency of occurrence of class-specific antibodies among normal subjects was 28% for immunoglobulin G (IgG), 98% for IgM, and 3% for IgA. Anti-GXM antibodies with kappa light chains occurred in 98% of normal subjects, while the occurrence of lambda light chains was 28%. Each of five subjects with high levels of anti-GXM IgG antibodies had readily detectable antibodies of the IgG2 isotype; two of the five subjects had readily detectable IgG1 antibody. An examination of sera from human immunodeficiency virus-infected patients showed that human immunodeficiency virus infection was accompanied by a significant decrease in the occurrence of IgM antibodies and anti-GXM antibodies with kappa light chains; these decreases occurred early in infection when CD4 counts were still > or = 500 cells per microliter. A slight but not statistically significant decrease in the occurrence of anti-GXM IgG antibodies was seen only in patients with CD4 levels of < 200 cells per microliter. Sera from normal subjects with high levels of anti-GXM IgG antibodies were examined to identify any contribution of the antibodies to complement activation or to opsonization of the yeast cells. An analysis of the kinetics for activation and binding of C3 to the yeast cell showed no pattern of quantitative or qualitative differences between sera with high or low levels of anti-GXM IgG antibodies. Phagocytosis studies showed that the naturally occurring IgG antibodies did not contribute to opsonization of the yeast cells.

Antibodies, Fungal↗
PubMed1994

T cell tumours of disparate phenotype in mice transgenic for Rbtn-2.

RBTN2 is a LIM domain protein which can be activated by the translocation t(11;14)(p13;q11) in childhood T cell acute leukaemia. Transgenic mice were examined in which rbtn2 protein is expressed in the T cell lineage. An average of 72% of these mice developed T cell tumours before 18 months of age, compared with 9% in transgenic mice expressing the related gene Rbtn-1. Rbtn2-induced tumours first appeared at 5 months of age and were clonal. They displayed a range of phenotypes, the most notable being CD3/CD45R double-positive cells. Tumours expressing either T cell receptor alpha/beta or gamma/delta heterodimers were found. Thus rbtn2 can promote tumours within a range of T cell types and maturities. The latency period before tumour development indicates that secondary events must occur before the onset of overt malignancy.

Adaptor Proteins, Signal Transducing↗
PubMed1992

An in vitro pharmacodynamic model to simulate antibiotic behavior of acute otitis media with effusion.

The purpose of this investigation was to develop an in vitro pharmacodynamic model (IVPM) that would simultaneously simulate in vivo serum and middle ear amoxicillin pharmacokinetic characteristics of acute (purulent) otitis media and then utilize the IVPM to assess amoxicillin-mediated killing of a type 7F Streptococcus pneumoniae (MIC = 0.002 mg/L). The IVPM consisted of a sterile central compartment and a membrane-bound "infected" peripheral compartment. Peak peripheral compartment amoxicillin concentrations occurred within 2 hr after its introduction into the central compartment and were approximately 30% of peak central compartment concentrations. Amoxicillin elimination from the central compartment was designed to provide a 1-hr t 1/2. Amoxicillin elimination from the peripheral compartment was slower than from the central compartment, with an average half-life of 2.3 hr. Significant concentration-related differences in maximal bacterial kill rates were not detected over the range of amoxicillin concentrations studied (0.26 to 14.6 mg/L). However, at peak central compartment amoxicillin concentrations of less than or equal to 2 mg/L, a lag phase in killing was observed. In general, the in vitro pharmacokinetic data derived from this model compare well with published in vivo data.

Amoxicillin↗
PubMed1992

Investigation of the early killing of Staphylococcus aureus by daptomycin by using an in vitro pharmacodynamic model.

The purpose of this study was to develop a pharmacodynamic model to describe the dependency of the rate of Staphylococcus aureus killing upon the concentration of daptomycin. A range of free (unbound) daptomycin concentrations ranging from 0.12 to 27 times the MIC were simulated in the peripheral compartment of a two-compartment pharmacokinetic model. Log-linear regression of free daptomycin concentrations versus growth or kill rate constants showed a significant correlation (r = -0.90; P less than 0.001). A Lineweaver-Burk plot of the reciprocal transformation of these data yielded a poor fit (r = -0.38; P greater than 0.05). When a Lineweaver-Burk-type regression analysis was performed on the reciprocal of the change in the rate constant rather than the rate constant itself, the result demonstrated good correlation (r = 0.90; P less than 0.0001). The observations were also well described by a sigmoidal maximum plateau pharmacologic effect model, in which the pharmacologic effect of daptomycin is a reduction in the bacterial exponential growth rate constant from the baseline in the absence of antibiotic to a lower (positive) growth or (negative) death rate constant observed in the presence of antibiotic. These data confirm that daptomycin exhibits concentration-dependent killing over a wide range of free daptomycin concentrations relative to the MIC and suggest that this is a saturable process similar to the Michaelis-Menten pharmacokinetic elimination of certain drugs.

Anti-Bacterial Agents↗
PubMed1991

Aminoglycoside resistance and aminoglycoside usage: ten years of experience in one hospital.

For 10 years the 700-bed Minneapolis Veterans Affairs Medical Center has conducted a policy of carefully controlled aminoglycoside usage and monitoring of resistance of over 25,000 aerobic and facultative gram-negative bacillary isolates to the aminoglycosides. On two occasions during the 1980s, our experience of introducing amikacin at a high level of usage was associated with a significant reduction in resistance to gentamicin and tobramycin among gram-negative bacilli. Rapid reintroduction of gentamicin usage in 1982 after the first amikacin period was associated with a significant and rapid increase in gentamicin and tobramycin resistance. However, in 1986, gentamicin was again reintroduced to this institution at an initially modest level, and the percentage of usage of gentamicin was gradually increased over a 15-month period without a significant change in resistance to gentamicin, tobramycin, or amikacin while maintaining an overall 68% gentamicin usage and 30% amikacin usage. Aminoglycoside usage (measured as patient days) rose steadily from under 2,000 patient days per quarter in 1980 and 1981 to over 3,000 days per quarter in 1985. Since 1985, usage has declined to under 2,500 patient days per quarter in 1990. This usage rise and fall occurred during a steadily declining daily patient census that was 590 in 1980 and 465 in 1989. A move to a new hospital building in June 1988 was associated with an additional significant decline in resistance to all aminoglycosides (P less than 0.05), continuing a trend that was evident for the year preceding the move. Resistance to aminoglycoside antibiotics is now at the lowest level in 10 years at this institution, with only one gram-negative organism, Pseudomonas aeruginosa, that exhibits more than 5% resistance to gentamicin and no gram-negative species that are more than 5% resistant to amikacin and tobramycin.

Amikacin↗
PubMed1990

Assessment of effects of protein binding on daptomycin and vancomycin killing of Staphylococcus aureus by using an in vitro pharmacodynamic model.

Initial clinical trials with daptomycin (2 mg/kg per day) were prematurely suspended because of unexplained treatment failures in patients with bacteremia who were treated with daptomycin, despite in vitro data indicating that the gram-positive cocci causing the infection were susceptible to daptomycin. One explanation for these clinical failures may relate to the relatively high degree of daptomycin protein binding (94%). To evaluate the impact of protein on daptomycin activity, a two-chamber in vitro pharmacodynamic model was used to study and compare the interaction between Staphylococcus aureus (clinical isolate) and either daptomycin or vancomycin, each in the presence and absence of physiologic human albumin concentrations. Low-dose (2 mg/kg) daptomycin, high-dose (6 mg/kg) daptomycin, and 10 mg of vancomycin per kg beta-phase elimination serum-concentration-versus-time curves were simulated by using this in vitro pharmacodynamic model. The bacterial kill rates by all three regimens were decreased in the presence of albumin (P less than 0.0002). The average times required for a 99% kill of the initial S. aureus inocula (approximately 5 x 10(7) CFU/ml) without albumin were 0.81 (low-dose daptomycin), 0.33 (high-dose daptomycin), and 6.18 (vancomycin) h. The average times required for a 99% kill of S. aureus with albumin were 7.66 (low-dose daptomycin), 0.95 (high-dose daptomycin), and 10.52 (vancomycin) h. These data demonstrate that, depending on the concentration of daptomycin, the presence of albumin can profoundly diminish the bactericidal activity of daptomycin.

Daptomycin↗