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Biomedical subjects

Carol Smith

Publications and source records attributed to Carol Smith.

15 recordsLinked to original sources
PubMed2006

The Spine Team Assessment for chronic back pain disability. Part 1: basic protocol and performance in 500 patients.

PURPOSE: For persons with chronic back pain disability, customized, effective, and efficient treatment depends on the initial assessment. Functional capacity evaluations and intake screenings for particular programs are not independent or goal-directed. This paper describes a standardized independent multidisciplinary assessment for treatment planning, and characteristic findings in a population of chronically disabled persons. METHODS: The Spine Team Assessment (STA), a (1/2)-day assessment including extensive intake information, evaluations by therapists and counselors, a team meeting with a physician, and a comprehensive report, was performed on 500 consecutive persons with chronic back pain. RESULTS: Representative findings included maximum cardiac performance of 5.33 (+/-4.08 SD) METS; Progressive Isoinertial Lifting Evaluation floor-to-waist of 36.4% (+/-23.9% of norms, and CESD depression scores of 24.7 (+/-13.5 SD). Fear and avoidance and poor physiologic effort were common. CONCLUSION: Deconditioning, psychosocial factors and functional deficits are common, complex, and variable among chronic back pain patients. This description of the STA provides a potentially reproducible standard for research into individualized treatment. The work provides benchmark data for independent multidisciplinary assessments.

Adult↗
PubMed2006

The Spine Team Assessment for chronic back pain disability. Part 2: team decision making and a preliminary outcome study.

PURPOSE: Back pain disability is complex, involving medical, physical, functional, social, and financial issues. This study aims to develop the first codified decision making process for individualized treatment planning. METHODS: In a multidisciplinary assessment protocol for chronic low back pain disability, the Spine Team Assessment (see Part I), a 'case law' qualitative approach to decision making began with a basic framework. Details were established over 103 cases at a community hospital. Through 500 more cases, a university spine program developed new exceptions, definitions, and rule clarifications. RESULTS: The final framework includes physical deconditioning, psychosocial factors, and potential for cure, with dozens of subcategories. Seventeen different combinations of therapy were recommended. Of 68 persons referred to one multidisciplinary treatment protocol, at 6 - 12 months the 17 completers had less work disability (31 vs. 62%, p = 0.032) and tended towards fewer subsequent diagnostic tests (17.6 vs. 34.7%) and less surgery (0 vs. 4). CONCLUSIONS: The data suggests that the process is complex, that customization did occur, and that at least one team decision led to better outcomes. While derived qualitatively, this decision-making tree provides a road map for less experienced teams and a precedent for researchers who wish to study individualized treatment.

Adult↗
PubMed2006

Risperidone irreversibly binds to and inactivates the h5-HT7 serotonin receptor.

Risperidone displays a novel mechanism of antagonism of the h5-HT7 receptor. Pretreatment of the cells with 5 or 20 nM risperidone, followed by removal of the drug from the media, renders the 5-HT7 receptors unresponsive to 10 microM 5-HT for at least 24 h. Thus, risperidone seems to be producing a rapid, long-lasting inactivation of the h5-HT7 receptor. Whole-cell radioligand binding studies indicate that risperidone interacts in an irreversible or pseudo-irreversible manner with the h5-HT7 receptor, thus producing the inactivation. Internalization of the h5-HT7 receptor was not detected by monitoring green fluorescent protein-labeled fluorescent forms of the h5-HT7 receptor exposed to 20 nM risperidone. Ten other antagonists were tested for h5-HT7-inactivating properties, and only 9-OH-risperidone and methiothepin were found to demonstrate the same anomalous properties as risperidone. These results indicate that the h5-HT7 receptor may possess unique structural features that allow certain drugs to induce a conformation resulting in an irreversible interaction in the intact membrane environment. This may indicate that the h5-HT7 receptor is part of a subfamily of G-protein-coupled receptors (GPCRs) possessing this property or that many GPCRs have the potential to be irreversibly blocked, but only select drugs can induce this effect. At the very least, the possibility that highly prescribed drugs, such as risperidone, are irreversibly antagonizing GPCR function in vivo is noteworthy.

Binding, Competitive↗
PubMed2005

Phase I clinical trial safety of DNA- and modified virus Ankara-vectored human immunodeficiency virus type 1 (HIV-1) vaccines administered alone and in a prime-boost regime to healthy HIV-1-uninfected volunteers.

DNA- and modified virus Ankara (MVA)-vectored candidate vaccines expressing human immunodeficiency virus type 1 (HIV-1) clade A-derived p24/p17 gag fused to a string of HLA class I epitopes, called HIVA, were tested in phase I trials in healthy, HIV-1/2-uninfected adults in Oxford, United Kingdom. Eighteen volunteers were vaccinated with pTHr.HIVA DNA (IAVI-001) alone, 8 volunteers received MVA.HIVA (IAVI-003) alone and 9 volunteers from study IAVI-001 were boosted with MVA.HIVA 9-14 months after DNA priming (IAVI-005). Immunogenicity results observed in these trials was published previously [Mwau M, Cebere I, Sutton J, Chikoti P, Winstone N, Wee EG-T, et al. An HIV-1 clade A vaccine in clinical trials: stimulation of HIV-specific T cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans. J Gen Virol 2004;85:911-9]. Here, we report on the safety of the two vaccines and the vaccine regimes. Overall, both candidate vaccines were safe and well tolerated. There were no reported vaccine-related adverse events over the 6-month period of the study and up to 2 years after the last vaccination. There were no moderate or severe local symptoms recorded after the pTHr.HIVA DNA intramuscular administration. Almost all participants experienced local reactogenicity events such as redness and induration after MVA.HIVA intradermal injection. Thus, the results from these initial small phase I trials administering the pTHr.HIVA DNA and MVA.HIVA vaccines either alone or in a prime-boost regime to healthy HIV-1/2-negative adults indicated that the vaccines were safe and warranted further testing of this approach in larger phase I/II studies.

AIDS Vaccines↗
PubMed2004

Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.

RATIONALE: In order to determine the possible relationship between antipsychotic drug properties and inverse agonist activity at h5HT6 and h5HT7 receptors, constitutively activated forms of these receptors were created by site-specific mutagenesis. Typical and atypical antipsychotic drugs were assayed for their potencies as inverse agonists at these mutated receptors. OBJECTIVES: Stable cell lines expressing constitutively activated forms of the h5HT6 and h5HT7 receptors were created. Typical and atypical antipsychotic drugs demonstrating high to moderate affinities for the h5HT6 and h5HT7 receptors were assayed for their potencies in reversing the agonist-independent activity (inverse agonist activity). RESULTS: The E322R h5HT6 mutant and the S267K h5HT7 mutant displayed sufficiently robust agonist-independent activity when expressed in stable cell lines to allow the detailed, concentration-dependent, investigation of the inverse agonist activity of typical and atypical antipsychotic drugs. All the drugs tested displayed inverse agonist activity at both the activated h5HT6 and h5HT7 receptors. Native forms of these receptors did not display any constitutive activity. Interestingly, atypical antipsychotic drugs displayed potent inverse agonist activity, relative to typical antipsychotic drugs, at the h5HT7 receptor. LSD displayed neutral antagonist properties at the mutant h5HT7 receptor. CONCLUSIONS: Site-specific mutations in the third intracellular loop of the G(s)-coupled h5HT6 and h5HT7 receptors produce constitutive activation. Antipsychotic drugs display inverse agonist activity at the activated receptors. The inverse agonist mechanism-of-action of the atypical antipsychotic drugs at the h5HT7 receptors may be different from the typical antipsychotic drugs as these drugs displayed far higher potencies as inverse agonists at the h5HT7 receptor.

Amino Acid Substitution↗
PubMed2004

Binding of tryptamine analogs at h5-HT1E receptors: a structure-affinity investigation.

Structure-affinity requirements for the binding of serotonin (5-HT) analogs at human 5-HT1E receptors were investigated by examining the affinities of >40 tryptamine-related compounds. No tryptamine analog was found to bind with substantially higher affinity than 5-HT. The results indicate that hydrogen bonding plays a key role in the 5-HT1E/receptor interaction. This finding was supported using quantitative structure-activity analysis (QSAR) techniques such as comparative molecular field analysis (CoMFA) and the program QsarIS.

Cell Line↗
PubMed2004

Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.

BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. METHODS: Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. RESULTS: Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. CONCLUSIONS: Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.

AIDS Vaccines↗
PubMed2004

Surgical fires--learn not to burn.

Consequences of a surgical fire can be deadly. Fires can occur in any setting where invasive procedures are performed. The basic principle to remember is that people start most fires, and people can prevent them. Fire safety training is essential so that staff members recognize the elements of the fire triangle and how these elements come together every day in their practice. Fire drills are an important aspect of this training. Education also must include review of written policies and procedures on fire safety and prevention. Staff members must learn how to respond to and fight fires on or in the patient. Fire safety and prevention must be a priority for managers and staff members.

Attitude of Health Personnel↗
PubMed2003

Binding of beta-carbolines at 5-HT(2) serotonin receptors.

A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-beta-carbolines was examined at 5-HT(2A) and 5-HT(2C) serotonin receptors. Whereas most of the methoxy-substituted derivatives typically displayed affinities similar to their unsubstituted parents, certain (particularly 8-substituted) bromo derivatives displayed enhanced affinity. A binding profile was obtained for selected beta-carbolines.

Binding Sites↗
PubMed2003

Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.

On the basis of an earlier finding that 5-methyl-5H-1,2,3,4-tetrahydropyrido[4,3-b]indole (5-methyl-1,2,3,4-tetrahydro-gamma-carboline; 1) binds at murine 5-HT(5A) receptors, preliminary structure-affinity studies were conducted. The present investigation extends these structure-affinity studies using human 5-HT(5A) receptors and examined additional analogues of 1. It was found (a) that there is little interspecies difference for the affinities of these compounds, (b) that an intact 1,2,3,4-tetrahydro-gamma-carboline ring system seems optimal and an N(2)-(3-(substituted-phenoxy)propyl) moiety results in high affinity, (c) that structurally related 1,2,3,4-tetrahydro-beta-carbolines also bind at 5-HT(5A) receptors, and (d) that all examined derivatives also possess affinity for 5-HT(2A) receptors. Evidence is provided that 5-HT(5A) and 5-HT(2A) receptor affinities probably do not covary and that it might be possible, with continued investigation, to develop analogues with enhanced 5-HT(5A) selectivity.

Animals↗
PubMed2002

Evaluation of isotryptamine derivatives at 5-HT(2) serotonin receptors.

On the basis that meta-chlorophenylpiperazine (mCPP; 1) is a nonselective 5-HT(2C) agonist, that benz-fused tryptamines (e.g., 5) display enhanced 5-HT(2) affinity, and that certain isotryptamines 3 reportedly bind with enhanced affinity and selectivity at 5-HT(2C) receptors, we prepared and examined a series of isotryptamine-related analogues as potentially selective 5-HT(2C) agonists. None of the compounds displayed selectivity for 5-HT(2C) versus 5-HT(2A) receptors. Detailed re-examination of a compound previously reported to display 100-fold 5-HT(2C) selectivity [i.e., S(+)-5,6-difluoro-alpha-methylisotryptamine] revealed that its selectivity versus 5-HT(2A) receptors was, at best, only 10-fold.

Drug Evaluation, Preclinical↗
PubMedDate not supplied

Unrestricted access to mental health services.

BACKGROUND: This study examines referrals to a nurse-led, community-based, acute psychiatric assessment and treatment centre in the north west of England which operates an open referral system. Data were collated over 12 months and the total number of assessments was 1,544. It focused on the appropriateness of emergency assessments, which accounted for 29 per cent (n = 446) of the total. In considering 'appropriateness' the authors examined each assessment by source, risk, diagnosis and outcome. CONCLUSION: The results show that professionals and non-health professionals, such as the patient themselves, carers or a voluntary group, are equally likely to make inappropriate referrals, but, overall, open access was used efficiently by both groups. The results also indicate that open access to the service enabled early intervention for high-risk client groups. Implications for professionals and services are discussed.

Community Health Centers↗