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1.
Environ Pollut ; 342: 122931, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38006995

RESUMO

Pollen and nectar can be contaminated with a range of pesticides, including insecticides, fungicides, and herbicides. Since these matrices are important food sources for pollinators and other beneficial insects, their contamination can represent a key route of exposure. However, limited knowledge exists with respect to pesticide residue levels and their dynamics in these matrices for many crops and active ingredients (AIs). We used controlled glasshouse studies to investigate the residue dynamics of a systemic (cyprodinil) and a contact (fludioxonil) fungicide in the floral matrices and other plant parts of courgette/zucchini (Cucurbita pepo L.). We aimed to better understand the processes behind residue accumulation and decline in pollen and nectar. Each AI was applied to plants, either by spraying whole plants or by targeted spraying onto leaves only. Samples of pollen, nectar, anthers, flowers, and leaves were taken on the day of application and each subsequent morning for up to 13 days and analysed for residues using LC-MS/MS. Significant differences in residue levels and dynamics were found between AIs and floral matrices. The present study allowed for the identification of potential routes by which residues translocate between tissues and to link those to the physicochemical properties of each AI, which may facilitate the prediction of residue levels in pollen and nectar. Residues of the contact AI declined more quickly than those of the systemic AI in pollen and nectar. Our results further suggest that the risk of oral exposure for pollinators may be considerably reduced by using contact AIs during the green bud stage of plants, but application of systemic compounds could still result in a low, but continuous long-term exposure for pollinators with limited decline.


Assuntos
Cucurbita , Fungicidas Industriais , Abelhas , Néctar de Plantas/química , Fungicidas Industriais/análise , Cucurbita/química , Polinização , Cromatografia Líquida , Espectrometria de Massas em Tandem , Flores , Pólen/química , Verduras
2.
Pain ; 161(6): 1341-1349, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32068667

RESUMO

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n = 142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single-center, double-blind, 12-week, 4-arm, parallel groups controlled clinical trial of (1) low concentration desipramine titrated to reach a serum concentration level of 15 to 65 ng/mL; (2) CBT and active placebo medication (benztropine mesylate, 0.125 mg); (3) low concentration desipramine and CBT; and (4) active benztropine placebo medication. Participants completed the Differential Description Scale and Roland Morris Disability Questionnaires before and after treatment as validated measures of outcomes in back pain intensity and disability, respectively. Participants within each condition showed significant reductions from pre-treatment to post-treatment in pain intensity (mean changes ranged from = -2.58 to 3.87, Cohen's d's = 0.46-0.84) and improvements in pain disability (mean changes = -3.04 to 4.29, Cohen's d's = 0.54-0.88). However, intent-to-treat analyses at post-treatment showed no significant differences between any condition, with small effect sizes ranging from 0.06 to 0.27. The results from this clinical trial did not support the hypothesis that desipramine, CBT, or their combination would be statistically superior to an active medicine placebo for reducing chronic back pain intensity or disability. Key limitations included recruiting 71% of the planned sample size and use of multiple inclusion/exclusion criteria that may limit generalizability to broader populations of patients with chronic back pain.


Assuntos
Dor Crônica , Terapia Cognitivo-Comportamental , Dor Lombar , Dor nas Costas , Dor Crônica/tratamento farmacológico , Desipramina/uso terapêutico , Humanos , Resultado do Tratamento
3.
Environ Pollut ; 249: 236-247, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30893636

RESUMO

In recent years, the impact of Plant Protection Products (PPPs) on insect pollinator decline has stimulated significant amounts of research, as well as political and public interest. PPP residues have been found in various bee-related matrices, resulting in governmental bodies worldwide releasing guidance documents on methods for the assessment of the overall risk of PPPs to different bee species. An essential part of these risk assessments are PPP residues found in pollen and nectar, as they represent a key route of exposure. However, PPP residue values in these matrices exhibit large variations and are not available for many PPPs and crop species combinations, which results in inaccurate estimations and uncertainties in risk evaluation. Additionally, residue studies on pollen and nectar are expensive and practically challenging. An extrapolation between different cropping scenarios and PPPs is not yet justified, as the behaviour of PPPs in pollen and nectar is poorly understood. Therefore, this review aims to contribute to a better knowledge and understanding of the fate of PPP residues in pollen and nectar and to outline knowledge gaps and future research needs. The literature suggests that four primary factors, the crop type, the application method, the physicochemical properties of a compound and the environmental conditions have the greatest influence on PPP residues in pollen and nectar. However, these factors consist of many sub-factors and initial effects may be disguised by different sampling methodologies, impeding their exact characterisation. Moreover, knowledge about these factors is ambiguous and restricted to a few compounds and plant species. We propose that future research should concentrate on identifying relationships and common features amongst various PPP applications and crops, as well as an overall quantification of the described parameters; in order to enable a reliable estimation of PPP residues in pollen, nectar and other bee matrices.


Assuntos
Poluentes Ambientais/análise , Resíduos de Praguicidas/análise , Néctar de Plantas/química , Pólen/química , Animais , Abelhas , Produtos Agrícolas , Insetos , Inseticidas/análise , Magnoliopsida , Polinização/efeitos dos fármacos , Medição de Risco
4.
Clin J Pain ; 35(4): 295-303, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30664550

RESUMO

OBJECTIVE: To compare the efficacy of mental health professional versus primary care nurse-delivered telehealth cognitive-behavioral therapy (CBT) and supportive care (SC) treatments for chronic low back pain, using data from 2 separate randomized controlled trials. Both trials were completed in the same hospital and used the same study design, research team, and outcome measures. MATERIALS AND METHODS: Participants from Study 1 (Mental Health Professional Study) (N=66; 2007 to 2011) and Study 2 (Nursing Study) (N=61; 2012 to 2016) were patients with chronic low back pain (≥4/10 intensity) randomized to either an 8-week CBT or an SC telehealth condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability (Roland Morris Disability Questionnaire [RMDQ]), pain intensity (Numeric Rating Scale [NRS]), depressive symptoms (Beck Depression Inventory 2 [BDI-2]), pain catastrophizing (Pain Catastrophizing Scale [PCS]), and overall improvement (Global Clinical Impressions [GCI]). RESULTS: Intent-to-treat analyses at posttreatment showed that scores on the RMDQ (Cohen d=0.33 to 0.55), NRS (d=0.45 to 0.90), PCS (d=0.21 to 0.41), and GCI (18.5% to 39.1%) improved significantly in both studies and in both treatments from pretreatment to posttreatment. Changes in BDI scores were inconsistent (d=-0.06 to 0.51). The analyses revealed no significant differences in treatment efficacy between the trained nurse versus the mental health professionals on the RMDQ, NRS, PCS, or GCI measures (P>0.20). DISCUSSION: Results from these clinical trials suggest that the benefits of home-based, telehealth-delivered CBT and SC treatments for chronic back pain were comparable when delivered by a primary care nurse or mental health professional.


Assuntos
Dor nas Costas/terapia , Pessoal de Saúde , Enfermeiras e Enfermeiros , Manejo da Dor/métodos , Psicoterapia , Telemedicina/métodos , Adulto , Idoso , Dor nas Costas/psicologia , Catastrofização , Competência Clínica , Terapia Cognitivo-Comportamental , Depressão/etiologia , Depressão/psicologia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
J Pain ; 19(9): 1033-1039, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29673974

RESUMO

This study evaluated a nurse-delivered, telehealth intervention of cognitive-behavioral therapy (CBT) versus supportive psychotherapy for chronic back pain. Participants (N = 61) had chronic back pain (pain "daily" ≥6 months at an intensity of ≥4 of 10 scale) and were randomized to an 8-week, 12-session, CBT or to supportive care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the numeric rating scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n = 30) showed significant improvements on the RMDQ (mean = 11.4 [SD = 5.9] vs 9.4 [SD = 6.1] at baseline and post-treatment, respectively, P < .05; d = .33), NRS (mean = 4.9 [SD = 2.1] vs 4.0 [SD = 1.9], respectively, P < .05; d = .45), and on the CGI (39.1% reporting "much improved" or "very much improved"). SC participants (n = 31) also showed significant improvements on the RMDQ (mean = 11.1 [SD = 5.4] vs 9.1 [SD = 5.2], respectively, P < .05; d = .38), the NRS, (mean = 5.0 [SD = 1.9] vs 3.8 [SD = 2.1], respectively, P < .05; d = .60), and 26.7% reporting "much improved" or "very much improved" on the CGI. Between groups comparisons of CBT and SC showed no differences on the study outcomes (Ps > .10). The results suggest that telehealth, nurse-delivered CBT, and SC treatments for chronic back pain can offer significant and relatively comparable benefits. PERSPECTIVE: This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Because of the high prevalence of chronic pain and the growing emphasis on nonopioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management.


Assuntos
Dor nas Costas/enfermagem , Dor nas Costas/terapia , Terapia Cognitivo-Comportamental/métodos , Manejo da Dor/métodos , Manejo da Dor/enfermagem , Adulto , Dor Crônica/enfermagem , Dor Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicoterapia/métodos , Telemedicina/métodos
6.
Clin J Pain ; 34(4): 322-327, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28877139

RESUMO

OBJECTIVE: The objective of this study was to evaluate the efficacy of a telephone-delivered, home-based cognitive-behavioral intervention for chronic low back pain in comparison to a matched supportive care (SC) treatment. METHODS: Participants (N=66) were patients with chronic back pain that were randomized to either an 8-week Cognitive-Behavioral Therapy (CBT) or a SC condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability, pain severity, and overall improvement. RESULTS: Intent-to-treat analyses at posttreatment showed that the treatment groups not show significantly different improvements in back pain disability (mean changes, -2.4 and -2.6 for CBT and SC, respectively; Cohen d, 0.49 and 0.55, respectively) or reductions in pain severity (mean changes, -0.9 and -1.4 for CBT and SC respectively; Cohen d, 0.50, and 0.90, respectively). Participants rated their overall improvement levels at 31% (CBT) versus 18.5% (SC). DISCUSSION: Results from this clinical trial suggest that home-based, telephone-delivered CBT and SC treatments did not significantly differ in their benefits for back pain severity and disability, and may warrant further research for applications to hospital settings. Major limitations included recruitment difficulties that underpowered primary analyses, the lack of objective improvement measures, and the absence of a usual care/untreated control group for comparisons.


Assuntos
Dor nas Costas/terapia , Dor Crônica/terapia , Terapia Cognitivo-Comportamental/métodos , Telefone , Atividades Cotidianas , Adulto , Idoso , Dor nas Costas/fisiopatologia , Dor nas Costas/psicologia , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Psicoterapia/métodos , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento
7.
Pain ; 157(7): 1499-1507, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26963844

RESUMO

Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, 2-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized patients with chronic back pain (daily pain for ≥6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (P < 0.0001) with subjects on gabapentin or placebo, reporting reductions of about 30% from baseline, but did not differ significantly between groups (P = 0.423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N = 72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least "Minimal Improvement" on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and nonradiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component.


Assuntos
Aminas/uso terapêutico , Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Dor Lombar/tratamento farmacológico , Ácido gama-Aminobutírico/uso terapêutico , Adulto , Idoso , Avaliação da Deficiência , Método Duplo-Cego , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Resultado do Tratamento
8.
Molecules ; 19(6): 8629-43, 2014 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-24962396

RESUMO

Polyhydroxyalkanoate (PHA) is a carbon storage polymer produced by certain bacteria in unbalanced nutrient conditions. The PHA forms spherical inclusions surrounded by granule associate proteins including the PHA synthase (PhaC). Recently, the intracellular formation of PHA granules with covalently attached synthase from Ralstonia eutropha has been exploited as a novel strategy for oriented enzyme immobilisation. Fusing the enzyme of interest to PHA synthase results in a bifunctional protein able to produce PHA granules and immobilise the active enzyme of choice to the granule surface. Functionalised PHA granules can be isolated from the bacterial hosts, such as Escherichia coli, and maintain enzymatic activity in a wide variety of assay conditions. This approach to oriented enzyme immobilisation has produced higher enzyme activities and product levels than non-oriented immobilisation techniques such as protein inclusion based particles. Here, enzyme immobilisation via PHA synthase fusion is reviewed in terms of the genetic designs, the choices of enzymes, the control of enzyme orientations, as well as their current and potential applications.


Assuntos
Aciltransferases/metabolismo , Enzimas Imobilizadas/metabolismo , Complexos Multienzimáticos/metabolismo , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Cupriavidus necator/enzimologia , Escherichia coli/enzimologia , Escherichia coli/genética , Lactococcus lactis/enzimologia , Lactococcus lactis/genética , Poli-Hidroxialcanoatos/biossíntese , Poliestirenos , Estrutura Quaternária de Proteína , Proteínas Recombinantes de Fusão/genética , Especificidade por Substrato
9.
Appl Environ Microbiol ; 80(10): 3062-71, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24610847

RESUMO

Bacterial inclusion bodies are aggregations of mostly inactive and misfolded proteins. However, previously the in vivo self-assembly of green fluorescent protein (GFP) fusions into fluorescent particles which displayed specific binding sites suitable for applications in bioseparation and diagnostics was demonstrated. Here, the suitability of GFP particles for enzyme immobilization was assessed. The enzymes tested were a thermostable α-amylase from Bacillus licheniformis, N-acetyl-d-neuraminic acid aldolase (NanA) from Escherichia coli, and organophosphohydrolase (OpdA) from Agrobacterium radiobacter. Respective GFP particles were isolated and could be stably maintained outside the cell. These enzyme-bearing GFP particles exhibited considerable stability across a range of temperature, pH, and storage conditions and could be recycled. The α-amylase-bearing particles retained activity after treatments at 4 to 85°C and at pHs 4 to 10, were stable for 3 months at 4°C, and could be recycled up to three times. OpdA-bearing particles retained degradation activity after treatments at 4 to 45°C and at pHs 5 to 10 and were able to be recycled up to four times. In contrast, the performance of NanA-bearing particles rapidly declined (>50% loss) after each recycling step and 3 months storage at 4°C. However, they were still able to convert N-acetylmannosamine and pyruvate to N-acetylneuraminic acid after treatment at 4 to 85°C and at pHs 4 to 11. Fluorescent GFP fusion particles represent a novel method for the immobilization and display of enzymes. Potential applications include diagnostic assays, biomass conversion, pharmaceutical production, and bioremediation.


Assuntos
Bacillus/enzimologia , Proteínas de Bactérias/química , Proteínas de Fluorescência Verde/química , Oxo-Ácido-Liases/química , Monoéster Fosfórico Hidrolases/química , alfa-Amilases/química , Agrobacterium tumefaciens/enzimologia , Agrobacterium tumefaciens/genética , Bacillus/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/genética , Enzimas Imobilizadas/metabolismo , Escherichia coli/enzimologia , Escherichia coli/genética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Concentração de Íons de Hidrogênio , Corpos de Inclusão/química , Corpos de Inclusão/genética , Corpos de Inclusão/metabolismo , Oxo-Ácido-Liases/genética , Oxo-Ácido-Liases/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Dobramento de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , alfa-Amilases/genética , alfa-Amilases/metabolismo
10.
Org Lett ; 14(10): 2650-3, 2012 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-22571756

RESUMO

A decarboxylative radical cyclization reaction has been developed for the synthesis of fluorenones. The reaction uses Ag(I)/K2S2O8 to oxidatively decarboxylate an aroylbenzoic acid to an aryl radical, which undergoes cyclization to afford fluorenone products in good yield.

11.
Pain Med ; 11(9): 1391-400, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20735749

RESUMO

OBJECTIVE: To assess whether pre-existing psychiatric diagnoses increase the likelihood of transitioning from sub-acute to chronic back pain. DESIGN: Prospective cohort study. METHODS: Men (N = 140) experiencing a first onset of low back pain (LBP) were examined for lifetime psychiatric disorders approximately 8 weeks post pain-onset using the Diagnostic Interview Schedule (DIS-III-R), then re-evaluated at 6 months after pain onset to determine who did or did not progress to pain chronicity. OUTCOME MEASURE: Transition to chronic pain and disability was based on 6-month self-report measures of pain intensity and perceived disability. RESULTS: Men with a pre-pain lifetime diagnosis of major depressive disorder had 5 times greater risk of transitioning to chronic LBP (odds ratio [OR] = 4.99; 95% confidence interval [CI] 1.49-16.76). Increased risk was also associated with a pre-pain lifetime diagnosis of generalized anxiety (OR = 2.45; 95% CI 1.06-5.68), post-traumatic stress (OR = 3.23; 95% CI 1.11-9.44), and with current nicotine dependence (OR = 2.49; 95% CI 1.15-5.40). There were no statistically significant effects for abuse or dependence of alcohol or other psychoactive substances. DISCUSSION: Lifetime history of major depression or a major anxiety disorder may represent potential psychosocial "yellow flags" for the transition to chronicity in men with first-onset LBP. Screening for lifetime depressive or anxiety disorders may identify individuals at higher risk, who may benefit from referral for more intensive rehabilitation.


Assuntos
Doença Crônica/psicologia , Dor Lombar/psicologia , Transtornos Mentais/complicações , Adolescente , Adulto , Humanos , Masculino , Transtornos Mentais/diagnóstico , Pessoa de Meia-Idade , Medição da Dor , Escalas de Graduação Psiquiátrica , Fatores de Risco , Tabagismo/complicações , Adulto Jovem
12.
Arch Phys Med Rehabil ; 90(4): 545-52, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19345767

RESUMO

OBJECTIVES: To evaluate the effects of a behavioral medicine intervention, relative to an attention control, in preventing chronic pain and disability in patients with first-onset, subacute low back pain (LBP) with limitations in work-role function. DESIGN: A 2-group, experimental design with randomization to behavioral medicine or attention control groups. SETTING: Orthopedic clinic at a Naval Medical Center. PARTICIPANTS: Sixty-seven participants with first-onset LBP of 6 to 10 weeks of duration and impairment in work function, of whom 50 completed all 4 therapy sessions and follow-up 6 months after pain onset. INTERVENTION: Four 1-hour individual treatment sessions of either behavioral medicine, focused on back function and pain education, self-management training, graded activity increases, fear reduction, and pain belief change; or attention control condition, focused on empathy, support, and reassurance. MAIN OUTCOME MEASURES: The primary outcome was proportion of participants classified as recovered, according to pre-established clinical cutoffs on standardized measures, signifying absence of chronic pain and disability at 6 months after pain onset. Secondary analyses were conducted on pain, disability, health status, and functional work category. Intervention credibility and pain belief manipulation checks were also evaluated. RESULTS: Chi square analyses comparing proportions recovered at 6 months after pain onset for behavioral medicine and attention control participants found relative rates of 52% versus 31% in the modified intent-to-treat sample (P=.09) and 54% versus 23% for those completing all 4 sessions and 6-month follow-up (P=.02). At 12 months, 79% of recovered and 68% of chronic pain participants still met criteria for their respective groups (P<.0001). Recovered participants also had higher rates of functional work status recovery at 12 months (recovered: 96% full duty and 4% light duty; chronic pain: 61% full duty, 18% light duty, and 21% medical discharge, respectively; P=.03). CONCLUSIONS: Early intervention using a behavioral medicine rehabilitation approach may enhance recovery and reduce chronic pain and disability in patients with first-onset, subacute LBP. Effects are stronger for participants attending all 4 sessions and the follow-up assessment.


Assuntos
Medicina do Comportamento/métodos , Conhecimentos, Atitudes e Prática em Saúde , Dor Lombar/reabilitação , Adulto , Doença Crônica , Progressão da Doença , Feminino , Humanos , Dor Lombar/classificação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Educação de Pacientes como Assunto/métodos , Modalidades de Fisioterapia , Qualidade de Vida , Resultado do Tratamento
13.
Curr Pain Headache Rep ; 13(2): 93-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19272274

RESUMO

Most antidepressants and anticonvulsants used in chronic pain syndromes have dose- and concentration-response curves developed for their application to treat psychiatric disorders. Because these are important clinical tools in medication management of psychiatric syndromes, it is reasonable to expect that utilizing concentration-effect relationships and known sources of pharmacokinetic variability for determining doses for analgesia may also improve treatment tolerability and outcomes. Efforts to identify dosing "therapeutic windows" or minimum "thresholds" for analgesic efficacy have provided useful guidance for initiating treatment, reducing toxicity, and assisting with decision making in the face of limited therapeutic response. This article reviews the strengths, limitations, and potential of therapeutic drug monitoring of antidepressants and anticonvulsants as analgesics for selected chronic pain syndromes.


Assuntos
Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Dor/tratamento farmacológico , Relação Dose-Resposta a Droga , Humanos , Doenças do Sistema Nervoso Periférico
14.
Clin J Pain ; 23(5): 409-16, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17515739

RESUMO

OBJECTIVES: Psychosocial variables are acknowledged predictors of back disability, but multivariate studies are needed to understand their independent and overlapping effects. The objective of this prospective cohort study was to evaluate independent and shared associations of psychosocial variables on work status after first onset of low back pain (LBP) in working men. METHODS: One hundred forty male military personnel reporting subacute, first onset LBP (2 mo average duration) completed an interview-based and survey-based psychosocial assessment within the domains of job satisfaction, stress and coping, pain perceptions and beliefs, perceived functional disability, and mood disturbance. Work status was assessed at baseline, 6 and 12-month postpain onset. RESULTS: In logistic regression analyses at baseline, work status was associated with pain interference and perceptions of physical impairment. Beyond 2 months, the extent to which pain was believed to interfere with function was the only significant predictor of subsequent changes in work status. Job dissatisfaction was associated with more impaired work status, but not after controlling for income. Depressive and anxious mood symptoms were prevalent but failed to explain additional variance in work status. DISCUSSION: After first onset of men with subacute LBP, self-reported pain intensity and functional limitation account for most of the variance in work status explained by psychosocial factors; however, the resulting disability can be accompanied by mild to moderate mood symptoms. This suggests that interventions to improve function, if commenced early in the course of subacute pain, might prevent work disability.


Assuntos
Dor Lombar/epidemiologia , Dor Lombar/psicologia , Adaptação Psicológica , Adulto , Afeto/fisiologia , Ansiedade/psicologia , Estudos de Coortes , Depressão/psicologia , Emprego , Humanos , Satisfação no Emprego , Modelos Logísticos , Estudos Longitudinais , Masculino , Militares , Transtornos do Humor/complicações , Transtornos do Humor/psicologia , Estudos Prospectivos , Apoio Social , Fatores Socioeconômicos , Estresse Psicológico/psicologia , Resultado do Tratamento
15.
J Clin Psychopharmacol ; 27(2): 135-42, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17414235

RESUMO

OBJECTIVE: Although antidepressants are widely prescribed as analgesics in chronic back pain, their clinical pharmacology is not well established. Norepinephrine transporter blockade seems to be essential for analgesia, but optimal concentrations are unknown. Fixed-dose studies of serotonin reuptake inhibitors are generally negative, but such studies cannot be interpreted clearly because efficacy might be detected if concentration-response relationships were known. We evaluated (1) the feasibility of conducting a controlled-concentration study of a norepinephrine (desipramine) and a serotonin reuptake (fluoxetine) inhibitor and (2) the relationship between achieved concentrations and analgesic response. METHODS: This single-center, 12-week, double-blind, prospective, controlled-concentration study randomized 121 chronic back pain patients without major depression to active placebo (benztropine mesylate) or to predetermined low, medium, or high concentrations of desipramine (targets were 50, 110, and 150 ng/mL, respectively) or fluoxetine (targets were 100, 200, and 400 ng/mL, respectively). Of these, 83 completed the trial: 38 withdrew primarily due to side effects. RESULTS: Manipulation check revealed significant overlap of assigned and achieved concentrations related to drug intolerability. Completers' analysis of achieved concentrations revealed reduction in pain intensity was significantly greater for low-concentration desipramine (<60 ng/mL, mean Descriptor Differential Scale [DDS], 4.5) compared with placebo (DDS 6.2), higher concentrations of desipramine (>60 ng/mL, DDS 7.9), and all concentrations of fluoxetine (P < 0.05, DDS 7.1). Significant improvement in everyday function mirrored findings for pain intensity. CONCLUSIONS: Preliminary evidence for a low-concentration "therapeutic window" for noradrenergic analgesia may warrant additional study.


Assuntos
Dor nas Costas/tratamento farmacológico , Desipramina/uso terapêutico , Fluoxetina/uso terapêutico , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/efeitos adversos , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Idoso , Cápsulas , Doença Crônica , Constipação Intestinal/induzido quimicamente , Desipramina/administração & dosagem , Desipramina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Fluoxetina/administração & dosagem , Fluoxetina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Medição da Dor/métodos , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Estudos Prospectivos , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Disfunções Sexuais Fisiológicas/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento , Xerostomia/induzido quimicamente
16.
Org Biomol Chem ; 4(22): 4118-26, 2006 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-17312966

RESUMO

A concise and convergent eight-step synthesis of the antifungal metabolite monocerin 1 is reported. The key step involves an allylsilane metathesis/aldehyde condensation sequence to establish the core 2,3,5-trisubstituted tetrahydrofuran. End-game approaches based around intramolecular Heck chemistry revealed an interesting example of formal 6-endo cyclisation, the origin of which was probed using model substrates. The synthesis was ultimately completed by a strategy involving stepwise oxidative cleavage of the C3-ethenyl substituent.


Assuntos
Lactonas/síntese química , Lactonas/química , Estrutura Molecular , Estereoisomerismo
18.
Pain ; 76(3): 287-296, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9718247

RESUMO

To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline (n = 5) had significantly (P < 0.05) better analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Dor Lombar/tratamento farmacológico , Nortriptilina/uso terapêutico , Adulto , Afeto/efeitos dos fármacos , Idoso , Antidepressivos Tricíclicos/efeitos adversos , Método Duplo-Cego , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Nortriptilina/efeitos adversos , Medição da Dor , Placebos , Qualidade de Vida , Perfil de Impacto da Doença
19.
Pain ; 73(2): 213-221, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9415508

RESUMO

Efforts to examine the process and risk of developing chronic back pain have relied generally upon retrospective study of individuals with already established pain. In an alternative approach to understanding the clinical course and evolution of low back disorders, a cohort of 76 men experiencing their first episode of back pain was assessed prospectively at 2, 6 and 12 months following pain onset. Standard measures of pain (Descriptor Differential Scale: DDS), disability (Sickness Impact Profile: SIP), and distress (Beck Depression Inventory: BDI) were employed to classify the sample into five groups: Resolved, Pain Only, Disability/Distress Only, Pain and Mild Disability/Distress, and Clinical Range. At both 6 and 12 months post pain onset, most (78%, 72% respectively) of the sample continued to experience pain. Many also experienced marked disability at 6 months (26%) and 12 months (14%). At 12 months, no participants had worsened relative to the 2-month baseline. Doubly multivariate analyses of variance (MANOVAs) were employed to compare baseline groups (Pain Only, Pain and Mild Disability/Distress, Clinical Range) on the DDS, SIP, and BDI across time. The group by time interaction from 2 through 12 months was reliable, with greatest change occurring in the Clinical Range group in disability and distress; interestingly, the decrease in pain was comparable among all groups. Follow-up tests across measures demonstrated greater change in the early (2-6-month) interval and relative stability in the later (6-12-month) interval. Comparison of those classified as 'improvers' with those who did not improve from 2 to 12 months showed similar findings. The clinical course of first onset back pain may be prolonged for many patients, and involves a continuum of related disability and distress. Individuals at risk for marked symptoms 1 year after an initial episode of back pain can be identified early, and prompt treatment might reduce the risk of pain chronicity.


Assuntos
Pessoas com Deficiência , Dor Lombar/terapia , Adolescente , Adulto , Idade de Início , Análise Custo-Benefício , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Resultado do Tratamento
20.
Pain ; 62(3): 349-355, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8657435

RESUMO

Previous studies have empirically defined clinical subgroups of chronic low back pain (CLBP) patients, based on differing patterns of pain, disability and emotional distress. Because these identified groups generally are comparable in terms of physical and demographic variables, variation in functional status cannot be adequately explained by medical or social factors. In the present study we evaluated whether other psychosocial factors (stress, coping attempts, and satisfaction with social supports) might differentiate the observed groups. A discriminate function analysis indicated that ratings of life adversity, coping, and social support statistically differentiate clinical groups of CLBP patients. Patients categorized as chronic pain syndrome (i.e., high levels of pain, disability and depression) reported greater life adversity, more reliance on passive/avoidant coping strategies, and less satisfaction with social support networks. Patients categorized as having good pain control (i.e., low levels of pain, disability and depression) reported less life adversity, less reliance on passive/avoidant coping strategies, and more satisfaction with social support networks. Finally, a mixed picture of less life adversity, but more reliance on passive/avoidant coping strategies and more satisfactory social support networks was reported by patients categorized in the positive adaptation to pain group (i.e., high levels of pain, but relatively low levels of disability and depression). These findings suggest that psychosocial factors may be important and complex correlates of multidimensional clinical presentations of CLBP. Psychosocial factors may also offer an avenue for intervention across 3 key dimensions of CLBP.


Assuntos
Dor nas Costas/classificação , Psicologia , Adaptação Psicológica , Adulto , Fatores Etários , Análise de Variância , Doença Crônica , Análise Discriminante , Humanos , Renda , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Apoio Social , Estresse Psicológico
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