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1.
West J Emerg Med ; 24(3): 436-446, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37278772

RESUMO

INTRODUCTION: The coronavirus 2019 (COVID-19) pandemic not only exacerbated barriers to healthcare but has also highlighted the trend toward increased vaccine hesitancy. Our goal was to improve COVID-19 vaccine uptake through a student-led, emergency department-based (ED) vaccination program. METHODS: This prospective, quality-improvement pilot program used medical and pharmacy student volunteers as COVID-19 vaccine screeners in a southern, urban, academic ED. Patients eligible for vaccination were offered either the Janssen-Johnson & Johnson or the Pfizer-BioNTech COVID-19 vaccine and were educated about vaccine concerns. Vaccine acceptance rates were recorded, as well as reasons for vaccine hesitancy, vaccine brand preferences, and demographics. The primary and secondary quantitative outcomes were overall vaccine acceptance and change in vaccine acceptance after student-provided education, respectively. We performed logistic regression to identify potential variables that correlated with vaccine acceptance. Guided by the Consolidated Framework for Implementation Research, focus group interviews with four key stakeholder groups explored implementation facilitators and barriers. RESULTS: We screened 406 patients for COVID-19 vaccination eligibility and current vaccine status, the majority of whom were unvaccinated. Of unvaccinated or partially vaccinated patients, vaccine acceptance before education was 28.3% (81/286), and vaccine acceptance after education was 31.5% (90/286) (% difference, 3.1% [95% CI 0.3%-5.9%], P=0.03). The most common hesitancy factors cited were concerns about side effects and safety. Results from the regression analysis indicated that increasing age and Black race were associated with an increased odds of vaccine acceptance. Focus groups revealed implementation barriers, including patient resistance and workflow issues, and facilitators, including student involvement and public health promotion. CONCLUSION: Using medical and pharmacy student volunteers as COVID-19 vaccine screeners was successful, and brief education provided by the students led to a modest increase in vaccine acceptance, with overall acceptance of 31.5%. Numerous educational benefits are described.


Assuntos
COVID-19 , Vacinas , Humanos , Vacinas contra COVID-19 , Vacina BNT162 , Estudos Prospectivos , COVID-19/prevenção & controle , Estudantes , Vacinação , Serviço Hospitalar de Emergência
2.
J Am Chem Soc ; 145(20): 11045-11055, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37167534

RESUMO

The ultraviolet photochemistry of the amino acids glycine, leucine, proline, and serine in their neutral forms was investigated using parahydrogen matrix-isolation spectroscopy. Irradiation by 213 nm light destroys the chirality of all three chiral amino acids as a result of the α-carbonyl C-C bond cleavage and hydrocarboxyl (HOCO) radical production. The temporal behavior of the Fourier-transform infrared spectra revealed that HOCO radicals rapidly reach a steady state, which occurs predominantly due to photodissociation of HOCO into CO + OH or CO2 + H. In glycine and leucine, the amine radicals generated by the α-carbonyl C-C bond cleavage rapidly undergo hydrogen elimination to yield methanimine and 3-methylbutane-1-imine, respectively. Breaking of the α-carbonyl C-C bond in proline appeared to yield 1-pyrroline, although due to its weak absorption it remains unconfirmed. In serine, additional products were formaldehyde and E/Z ethanimine. The present study shows that the direct production of HOCO previously observed in α-alanine generalizes to other amino acids of varying structure. It also revealed a tendency for amino acid photolysis to form imines rather than amine radicals. HOCO should be useful in the search for amino acids in interstellar space, particularly in combination with simple imine molecules.


Assuntos
Aminoácidos , Glicina , Aminoácidos/química , Leucina , Glicina/química , Prolina , Serina , Aminas
3.
J Phys Chem Lett ; 12(50): 11992-11997, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34889613

RESUMO

UV photodissociation of α-alanine was studied by parahydrogen matrix isolation infrared spectroscopy. The temporal behavior of Fourier transform infrared spectra revealed that UV irradiation at 213 nm yielded the HOCO radical as a direct photoproduct from the S2 excited state. The concentration of HOCO quickly approached a steady state due to secondary photodissociation of HOCO to produce CO2 + H or CO + OH. On the other hand, no photoproducts were detected by S1 excitation at 266 nm. Irradiation of fully deuterated α-alanine at 213 nm yielded ∼2 times more cis-DOCO radicals than the lower energy isomer trans-DOCO, indicating that the conformation of the hydroxyl group is fairly well-preserved upon photodissociation of α-alanine. The present study suggests that HOCO may be a good tracer species in the search for amino acids in interstellar space.


Assuntos
Alanina/química , Dióxido de Carbono/química , Raios Ultravioleta , Isomerismo , Fotólise/efeitos da radiação , Teoria Quântica
4.
Pharmacy (Basel) ; 9(4)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34842802

RESUMO

Medicines optimisation for those with respiratory conditions can have a significant impact on clinical outcomes and substantial efficiency gains for health care. Consultant pharmacists are experts working at the top of their specialism in four main pillars of practice, namely clinical care, leadership, education and training, and research and development. A consultant respiratory pharmacist has recently been appointed at a large Health and Social Care Trust in Northern Ireland to provide expert care and clinical leadership for the medicines optimisation agenda with regards to respiratory care in Northern Ireland. Alongside clinical practice, leadership, and service development, emphasis will be placed on monitoring and evaluating the work of the consultant respiratory pharmacist with a view to gathering the necessary evidence to support the case for further investment in such consultant pharmacist posts in the region. This short communication article outlines some of the clinical and economic factors associated with the decisions to invest in the consultant pharmacist model of care in Northern Ireland.

5.
Phys Chem Chem Phys ; 23(7): 4094-4106, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33586746

RESUMO

Samples of H2O, HDO, and D2O were isolated in solid parahydrogen (pH2) matrices and irradiated by vacuum ultraviolet (VUV) radiation at 147 nm. Fourier-Transform Infrared (FTIR) spectra showed a clear depletion of D2O and an enrichment of both HDO and H2O by 147 nm irradiation. These irradiation-dependent changes are attributed to the production of OH and/or OD radicals through photodissociations of H2O, HDO, and D2O. The radicals subsequently react with the hydrogen matrix, leading to the observed enrichment of H2O. No trace of isolated OH or OD was detected in the FTIR spectra, indicating that the OH/OD radicals react with the surrounding matrix hydrogen molecules via quantum tunneling within our experimental timescale. The observed temporal changes in concentrations, especially the increase of HDO concentration during VUV irradiation, can be interpreted by a model with a rapid conversion from orthohydrogen (oH2) to pH2 in water-oH2 complexes upon VUV photodissociation, indicating either the acceleration of the nuclear spin conversion (NSC) of H2 due to the magnetic moment of the intermediate OH/OD radical, or the preferential reaction of the OH/OD radical with a nearby oH2 molecule over other pH2 molecules. We have also identified and quantified an anomalously slow NSC of H2O and D2O complexed with oH2 in solid pH2.

6.
Infect Immun ; 88(12)2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32928963

RESUMO

During the natural enzootic life cycle of Borrelia burgdorferi (also known as Borreliella burgdorferi), the bacteria must sense conditions within the vertebrate and arthropod and appropriately regulate expression of genes necessary to persist within these distinct environments. bb0345 of B. burgdorferi encodes a hypothetical protein of unknown function that is predicted to contain an N-terminal helix-turn-helix (HTH) domain. Because HTH domains can mediate protein-DNA interactions, we hypothesized that BB0345 might represent a previously unidentified borrelial transcriptional regulator with the ability to regulate events critical for the B. burgdorferi enzootic cycle. To study the role of BB0345 within mammals, we generated a bb0345 mutant and assessed its virulence potential in immunocompetent mice. The bb0345 mutant was able to initiate localized infection and disseminate to distal tissues but was cleared from all sites by 14 days postinfection. In vitro growth curve analyses revealed that the bb0345 mutant grew similar to wild-type bacteria in standard Barbour-Stoenner-Kelley II (BSK-II) medium; however, the mutant was not able to grow in dilute BSK-II medium or dialysis membrane chambers (DMCs) implanted in rats. Proteinase K accessibility assays and whole-cell partitioning indicated that BB0345 was intracellular and partially membrane associated. Comparison of protein production profiles between the wild-type parent and the bb0345 mutant revealed no major differences, suggesting BB0345 may not be a global transcriptional regulator. Taken together, these data show that BB0345 is essential for B. burgdorferi survival in the mammalian host, potentially by aiding the spirochete with a physiological function that is required by the bacterium during infection.


Assuntos
Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/metabolismo , Regulação Bacteriana da Expressão Gênica/genética , Interações entre Hospedeiro e Microrganismos/genética , Lipoproteínas/metabolismo , Doença de Lyme/microbiologia , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Borrelia burgdorferi/crescimento & desenvolvimento , Borrelia burgdorferi/patogenicidade , Biologia Computacional , Feminino , Lipoproteínas/química , Lipoproteínas/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes , Spirochaetales/genética , Spirochaetales/metabolismo , Spirochaetales/patogenicidade
7.
Int J Pediatr Otorhinolaryngol ; 134: 110013, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32247220

RESUMO

BACKGROUND: Controversy exists on management of lymphatic malformations, with schools of thought advocating for observation, surgery or sclerotherapy. This study sought to examine outcomes after surgical resection of pediatric cervicofacial macrocystic lymphatic malformations (MLM). METHODS: Case series with planned data collection on pediatric patients with cervicofacial MLM who underwent surgical resection at a tertiary referral center for vascular anomalies from January 1995 to June 2016. For consistency in patient population analysis, patients who had pre-surgical sclerotherapy or had mixed or microcystic disease were excluded. The main outcome was complete response rate (CR) and long-term recurrence-free survival (RFS). RESULTS: Sixty-three patients who underwent excision of MLM were included, 52.4% were female, 77.8% Caucasian. The majority had de Serres stage I-III (96.8%) affecting the neck (71.4%). Patients were discharged the same day (28.6%), or had a 1 day median length-of-stay (interquartile range (IQR) = 2). Surgical complications included seroma/hematoma (9.5%), transient nerve weakness (facial nerve, sympathetic chain, or phrenic nerve, 6.3%), and infection (1.6%). On long-term follow-up (median: 12 months, IQR 1-43 months), a single surgery achieved CR in 90.5% of patients. RFS was achieved in 86% of patients in our observation period of up to 15 years. Most patients requiring a second intervention failed within 6-months of initial procedure (4/5 patients, 90%); associated factors included bilaterality, advanced staging, and partial response at first-follow-up (p = 0.0051, 0.0051, and <0.0001, respectively). CONCLUSIONS: Surgery is safe and effective as first line treatment for selected MLM. For stage I-III MLM CR and long-term RFS can be achieved with a single surgery. A direct and randomized comparison of treatment modalities is needed.


Assuntos
Face/anormalidades , Anormalidades Linfáticas/patologia , Anormalidades Linfáticas/cirurgia , Pescoço/anormalidades , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Escleroterapia , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
8.
J Phys Chem B ; 123(20): 4392-4399, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31038312

RESUMO

Amino acids are the building blocks of proteins, and their detection in outer space thus has implications on the origin of life. They form a zwitterionic structure in aqueous environments while adopting a neutral configuration in the gas phase. We perform an experimental and computational study on the number of water molecules needed for zwitterion formation of ß-alanine. Our density functional theory investigation reveals that a minimum of five water molecules are required to form and stabilize the zwitterion. A characteristic connecting water molecule located between the COO- and NH3+ groups is found to enhance the stability. This water molecule is also involved in a characteristic infrared active vibration at ≈1560 cm-1, which is slightly shifted with the number of surrounding water molecules and is located in a spectral region outside of water vibrations. A corresponding infrared signal is found in high-resolution experimental spectra of ß-alanine and water in a solid para-hydrogen matrix.


Assuntos
Teoria da Densidade Funcional , Água/química , beta-Alanina/química , Estrutura Molecular , Espectrofotometria Infravermelho
9.
J Phys Chem Lett ; 9(22): 6475-6479, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30376636

RESUMO

With the use of solid parahydrogen in matrix isolation spectroscopy becoming more commonplace over the past few decades, it is increasingly important to understand the behavior of molecules isolated in this solid. The mobility of molecules in solid parahydrogen can play an important role in the dynamics of the system. Water molecules embedded in solid parahydrogen as deposited were found to be mobile at 4.0 K on the time scale of a few days. The diffusion at this temperature must be due to quantum tunneling in solid parahydrogen. The diffusion dynamics were analyzed based on the theory of nucleation. The concentration dependence on the diffusion rate indicates that there might be correlated motion of water molecules, a signature of quantum diffusion. We find that both water monomers and water dimers migrate in solid parahydrogen and provide insight into the behavior of molecules embedded in this quantum crystal.

10.
Pain Rep ; 3(4): e669, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30123859

RESUMO

INTRODUCTION: Cognitive performance and inflammation are altered in people with chronic low back pain (CLBP). Yet, the magnitude of these changes has been unclear because of the potential influence of opioid analgesics. OBJECTIVES: This cross-sectional pilot study aimed to explore whether patients with CLBP receiving long-term opioid analgesics differed from patients not taking opioids on measures of cognitive performance and plasma cytokine concentrations. METHODS: Patients with CLBP who were either taking (N = 18) or not taking (N = 22) opioids daily for 3 or more months were recruited from a tertiary care private hospital and compared with healthy adults (N = 20). All groups were administered validated questionnaires to assess depression, anxiety, and stress; a cognitive test of memory, attention, and executive function; and a peripheral blood draw to measure proinflammatory (IL-1ß, IL-2, IL-8, IL-12p70, TNF-α, and IFN-γ), anti-inflammatory (IL-4, IL-10, and IL-13), and pleiotropic (IL-6) cytokine concentrations. Patients also completed pain-specific questionnaires. RESULTS: Patients receiving opioid analgesics performed significantly (P < 0.05) worse in attention and had significantly (P < 0.05) lower pain self-efficacy beliefs than those patients not taking opioids. Patient groups did not differ in mean pain severity or pain interference scores, tests of memory and executive function, and mean plasma cytokine concentrations, despite long-term opioid analgesics. CONCLUSION: Patients receiving long-term opioid analgesics for CLBP have minor differences when compared with patients not taking opioids. This has important clinical implications when considering long-term treatment for patients with CLBP.

11.
Pain Med ; 15(12): 1992-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25287811

RESUMO

Since its formation, the Faculty of Pain Medicine (FPM) has grown into an organization with 369 fellows. It has 29 accredited pain medicine training units in Australia, New Zealand, Hong Kong, and Singapore. This article reviews the history of its birth and subsequent growth. The FPM fellowship is widely recognized as a high-quality qualification, based on a sound curriculum, excellent clinical exposure, and robust continuing professional development. But how does the Faculty position itself for the future? The Faculty's 5-year Strategic Plan (from 2013 to 2017) sets out its vision "to reduce the burden of pain in society through education, advocacy, training and research."


Assuntos
Educação de Pós-Graduação em Medicina/métodos , Manejo da Dor/história , Sociedades Médicas/história , Austrália , Medicina Clínica/educação , Medicina Clínica/organização & administração , Bolsas de Estudo , História do Século XX , História do Século XXI , Humanos , Nova Zelândia , Sociedades Médicas/organização & administração
12.
Pain Physician ; 17(5): 401-14, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25247898

RESUMO

BACKGROUND: Long-term opioid use for chronic non-cancer pain has increased substantially in recent years despite the paucity of strong supporting scientific data and concerns regarding adverse effects and potential misuse. STUDY DESIGN: Review and summary of practice guidelines available on PubMed and Cochrane databases as well as on the Internet on chronic opioid therapy from June 2004 to June 2013. OBJECTIVE: To review expert-developed practice guidelines on chronic opioid therapy, published in different countries over the past decade in order to reveal similar principles of therapy and to provide useful information and references for future development of opioid guidelines to identify adequately supported practice points and areas in need of further scientific evidence. METHOD: Seven guidelines were identified as pertaining specifically to the long-term use of opioids for general chronic non-cancer pain from an initial search of the PubMed/Medline and Cochrane databases using combinations of the search terms "opioid," "chronic opioid therapy," "chronic pain," "chronic non-cancer pain," "chronic non-malignant pain," "guidelines," "practice guidelines," and "clinical practice guidelines," filtered to include only articles on humans published in the English language over the past 10 years. RESULTS: All guidelines espouse an individual approach to management, beginning with a comprehensive patient evaluation, with particular focus on eliciting factors that may indicate potential drug misuse and abuse, and a trial of therapy to determine the course of treatment. Goals of treatment should be adequately discussed with and consented to by the patient. Opioids are generally not recommended as first-line therapy but, when used, clinicians should closely monitor patients for loss of response, adverse effects or aberrant behavior, and revise the treatment plan accordingly. Urine drug testing (UDT) may be used as a tool to monitor for aberrant behavior or drug misuse; opioid rotation may be considered when loss of response or adverse effects are a concern, at a starting dose lower than the calculated equianalgesic dose. LIMITATIONS: Information on some African nations, countries in the Middle-East, and Pacific Islands is not available and therefore was not included in this review. CONCLUSION: There is a growing body of scientific evidence to support opioid use in chronic pain. Future work should focus on continuing to generate good-quality evidence on the long-term benefits of opioid therapy, as well as scientific data to guide drug choice and dosing for specific conditions, populations, and situations.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Manejo da Dor/métodos , Guias de Prática Clínica como Assunto/normas , Analgésicos Opioides/administração & dosagem , Humanos , Manejo da Dor/normas
13.
Infect Immun ; 82(10): 4292-306, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25069985

RESUMO

The Lyme disease spirochete, Borrelia burgdorferi, occupies both a tick vector and mammalian host in nature. Considering the unique enzootic life cycle of B. burgdorferi, it is not surprising that a large proportion of its genome is composed of hypothetical proteins not found in other bacterial pathogens. bb0238 encodes a conserved hypothetical protein of unknown function that is predicted to contain a tetratricopeptide repeat (TPR) domain, a structural motif responsible for mediating protein-protein interactions. To evaluate the role of bb0238 during mammalian infection, a bb0238-deficient mutant was constructed. The bb0238 mutant was attenuated in mice infected via needle inoculation, and complementation of bb0238 expression restored infectivity to wild-type levels. bb0238 expression does not change in response to varying culture conditions, and thus, it appears to be constitutively expressed under in vitro conditions. bb0238 is expressed in murine tissues during infection, though there was no significant change in expression levels among different tissue types. Localization studies indicate that BB0238 is associated with the inner membrane of the spirochete and is therefore unlikely to promote interaction with host ligands during infection. B. burgdorferi clones containing point mutations in conserved residues of the putative TPR motif of BB0238 demonstrated attenuation in mice that was comparable to that in the bb0238 deletion mutant, suggesting that BB0238 may contain a functional TPR domain.


Assuntos
Proteínas de Bactérias/metabolismo , Borrelia burgdorferi/patogenicidade , Doença de Lyme/microbiologia , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/genética , Borrelia burgdorferi/genética , Análise Mutacional de DNA , Modelos Animais de Doenças , Feminino , Deleção de Genes , Teste de Complementação Genética , Camundongos , Camundongos Endogâmicos C3H , Mutação Puntual , Ratos Sprague-Dawley , Fatores de Virulência/genética
14.
Infect Immun ; 82(8): 3186-98, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24842928

RESUMO

Decorin-binding protein A (DbpA) of Borrelia burgdorferi mediates bacterial adhesion to heparin and dermatan sulfate associated with decorin. Lysines K82, K163, and K170 of DbpA are known to be important for in vitro interaction with decorin, and the DbpA structure, initially solved by nuclear magnetic resonance (NMR) spectroscopy, suggests these lysine residues colocalize in a pocket near the C terminus of the protein. In the current study, we solved the structure of DbpA from B. burgdorferi strain 297 using X-ray crystallography and confirmed the existing NMR structural data. In vitro binding experiments confirmed that recombinant DbpA proteins with mutations in K82, K163, or K170 did not bind decorin, which was due to an inability to interact with dermatan sulfate. Most importantly, we determined that the in vitro binding defect observed upon mutation of K82, K163, or K170 in DbpA also led to a defect during infection. The infectivity of B. burgdorferi expressing individual dbpA lysine point mutants was assessed in mice challenged via needle inoculation. Murine infection studies showed that strains expressing dbpA with mutations in K82, K163, and K170 were significantly attenuated and could not be cultured from any tissue. Proper expression and cellular localization of the mutated DbpA proteins were examined, and NMR spectroscopy determined that the mutant DbpA proteins were structurally similar to wild-type DbpA. Taken together, these data showed that lysines K82, K163, and K170 potentiate the binding of DbpA to dermatan sulfate and that an interaction(s) mediated by these lysines is essential for B. burgdorferi murine infection.


Assuntos
Adesinas Bacterianas/metabolismo , Borrelia burgdorferi/fisiologia , Doença de Lyme/microbiologia , Lisina/metabolismo , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Substituição de Aminoácidos , Animais , Borrelia burgdorferi/genética , Cristalografia por Raios X , Análise Mutacional de DNA , Lisina/química , Lisina/genética , Camundongos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Conformação Proteica
15.
Expert Opin Pharmacother ; 13(10): 1527-33, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22725707

RESUMO

INTRODUCTION: Fibromyalgia (FM) is the most common cause of chronic widespread body pain in humans. Co-morbidities include sleep disturbance, fatigue, impaired physical functioning, altered mood and negative effects on health-related quality of life. Pregabalin inhibits presynaptic release of pronociceptive neurotransmitters in the CNS; this likely underpins its therapeutic benefit in patients with FM. AREAS COVERED: This review addresses pregabalin pharmacokinetics, efficacy and adverse event (AE) profiles from randomized controlled trials and open-label extension studies in patients with FM. These effects are compared with those of the serotonin norepinephrine reuptake inhibitors, duloxetine and milnacipran that also have FDA approval for the treatment of fibromyalgia. EXPERT OPINION: At the approved dosages, oral pregabalin has at most a moderate therapeutic benefit above placebo with tolerable side-effects, in no more than 50% of patients with FM. Durability of clinically meaningful (≥ 30%) pain relief in pregabalin-responders has been demonstrated for at least 6-months, but longer-term studies are required as most patients have symptoms for decades. Exclusion of patients with common co-morbidities from the pregabalin RCTs in FM raises questions on the generalizability of the RCT findings to the typical patient seen in clinical practice and so additional investigation is required.


Assuntos
Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Ácido gama-Aminobutírico/análogos & derivados , Analgésicos/farmacologia , Humanos , Pregabalina , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Ácido gama-Aminobutírico/farmacologia , Ácido gama-Aminobutírico/uso terapêutico
16.
Pain Med ; 11(4): 550-61, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20202139

RESUMO

OBJECTIVE: This preliminary study assessed possible relationships between plasma and/or cerebrospinal fluid (CSF) concentrations of the pleiotropic cytokine, interleukin (IL)-6, the anti-inflammatory cytokine, IL-10, and levels of pain reported by patients receiving intrathecal (i.t.) opioids. DESIGN: A prospective study quantifying IL-6 and IL-10 concentrations using enzyme-linked immunoassays in samples of plasma and CSF as well as assessment of pain scores in patients receiving intrathecal opioids for management of chronic noncancer pain. SETTING: Outpatient pain clinics. PATIENTS: Patients with chronic pain receiving intrathecal morphine or hydromorphone alone or in combination with local anesthetics. INTERVENTIONS: Two groups of patients were studied. The first group (n = 50) had been receiving long-term i.t. opioids by chronically implanted pump for approximately 5 years; paired samples of plasma and CSF were collected at the time of i.t. pump refill. For the second patient group (n = 10), possible temporal changes in the plasma and/or CSF concentrations of IL-6 and IL-10 were investigated for 3 months after initiation of i.t. opioid infusions. RESULTS: For patients receiving long-term i.t. opioid infusions, there were significant inverse correlations (P < or = 0.05) between pain intensity and the plasma (but not CSF) IL-10 and IL-6 concentrations. Despite the considerable inter-patient variability in the CSF concentrations of IL-6 in the long-term cohort, the mean CSF IL-6 concentration was approximately fivefold higher in patients receiving long-term i.t. opioids relative to those receiving i.t. opioids for only 3 months. CONCLUSIONS: The significant inverse correlations observed between pain intensity and the plasma IL-6 and IL-10 concentrations in patients receiving longterm i.t. opioids for chronic pain management, suggests that these cytokines are worthy of further investigation as possible biomarkers of persistent pain.


Assuntos
Analgésicos Opioides , Bombas de Infusão Implantáveis , Injeções Espinhais , Interleucina-10 , Interleucina-6 , Dor/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Feminino , Humanos , Interleucina-10/sangue , Interleucina-10/líquido cefalorraquidiano , Interleucina-6/sangue , Interleucina-6/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Clínicas de Dor , Medição da Dor , Estudos Prospectivos , Resultado do Tratamento
17.
J Pain ; 11(5): 462-71, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19962354

RESUMO

UNLABELLED: The aim of this randomized double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of pregabalin in combination with oxycodone or placebo, in patients with either postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN). After a 7-day washout period, 62 patients were randomized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week. Patients were then started on open-label pregabalin (75, 150, 300 and 600 mg/day) according to a forced titration dosing regimen, while continuing the same dosage of oxycodone or placebo for 4 weeks. The primary efficacy measure was a decrease in the pain-intensity score of at least 2cm and a pain score <4cm measured using a 10-cm visual analogue scale (VAS) following pregabalin dosage escalation and treatment for 4 weeks. Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale. There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain. PERSPECTIVE: Peripheral neuropathic pain presents commonly in clinical practice, and 2 of its most prevalent types are PHN and PDN. Currently available treatments provide some degree of pain relief in approximately 40-60% of patients, leaving the remainder with unremitting pain. Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN, it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin.


Assuntos
Analgésicos Opioides/uso terapêutico , Analgésicos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Neuralgia/tratamento farmacológico , Oxicodona/uso terapêutico , Ácido gama-Aminobutírico/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxicodona/administração & dosagem , Oxicodona/efeitos adversos , Dor/tratamento farmacológico , Medição da Dor , Pregabalina , Sono/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/uso terapêutico
18.
Opt Express ; 16(3): 1583-9, 2008 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-18542236

RESUMO

A local optical surface representation as a sum of basis functions is proposed and implemented. Specifically, we investigate the use of linear combination of Gaussians. The proposed approach is a local descriptor of shape and we show how such surfaces are optimized to represent rotationally non-symmetric surfaces as well as rotationally symmetric surfaces. As an optical design example, a single surface off-axis mirror with multiple fields is optimized, analyzed, and compared to existing shape descriptors. For the specific case of the single surface off-axis magnifier with a 3 mm pupil, >15 mm eye relief, 24 degree diagonal full field of view, we found the linear combination of Gaussians surface to yield an 18.5% gain in the average MTF across 17 field points compared to a Zernike polynomial up to and including 10th order. The sum of local basis representation is not limited to circular apertures.


Assuntos
Desenho Assistido por Computador , Desenho de Equipamento/métodos , Análise de Falha de Equipamento/métodos , Lentes , Modelos Teóricos , Simulação por Computador
19.
CNS Drugs ; 22(5): 417-42, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18399710

RESUMO

Neuropathic pain is a persistent pain condition that develops secondary to nerve injury. The two most common types of peripheral neuropathic pain are post-herpetic neuralgia (PHN) and painful diabetic neuropathy (PDN). Amitriptyline, nortriptyline, desipramine and imipramine are TCAs that have been shown to be effective for the symptomatic relief of PHN and PDN. Serotonin noradrenaline reuptake inhibitors (SNRIs) such as venlafaxine and duloxetine have been shown to be very promising for the treatment of PDN with fewer adverse effects than TCAs. Selective serotonin reuptake inhibitors (SSRIs) were shown in a number of studies to have some efficacy in relieving PDN-related pain, yet other studies of the SSRIs have demonstrated conflicting outcomes. Most of the older antiepileptic studies were performed in patients with PDN; consequently, little is known about the efficacy of these drugs in patients with PHN. Carbamazepine, phenytoin and valproic acid were shown to be effective in ameliorating PDN-related pain. Other antiepileptic agents, including lamotrigine, oxcarbazepine and topiramate, have demonstrated some beneficial effects for the treatment of PDN, although they were also found to be ineffective in some PDN studies. alpha2delta Ligands such as gabapentin and pregabalin have been proven to be effective for the treatment of PHN and PDN in a number of large placebo-controlled trials. These drugs are useful not only in relieving pain but also in improving quality of life. Although the use of opioids for the treatment of neuropathic pain is controversial, a number of studies support the efficacy and safety of opioids in the treatment of neuropathic pain. Of these, oxycodone and tramadol have been shown to be superior to placebo for the treatment of PHN and PDN. A number of small studies have shown that dextromethorphan was effective in patients with PDN but not in patients with PHN. Topical agents such as lidocaine 5% patches and topical capsaicin are useful in ameliorating pain in patients with PHN but these agents are unsatisfactory for use as a sole agent. Although a number of drug treatments are available for the symptomatic relief of neuropathic pain symptoms, these agents do not provide satisfactory relief in all patients. For these patients, other treatment alternatives such as combination drug therapy that produces pain relief via distinctly different mechanisms may be successful. The purpose of this review is to compare the efficacy and limitations of currently available pharmacological treatments for the symptomatic relief of PHN and PDN, and to discuss the potential of combination therapy in PHN and PDN.


Assuntos
Analgésicos Opioides/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Neuropatias Diabéticas/tratamento farmacológico , Neuralgia Pós-Herpética/tratamento farmacológico , Animais , Neuropatias Diabéticas/complicações , Humanos , Neuralgia Pós-Herpética/complicações
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