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1.
S Afr Med J ; 112(2): 13498, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35139986

RESUMO

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to be highly effective in the treatment of rheumatic conditions, but may increase the risk of infections. Development of tuberculosis (TB) while on bDMARD therapy is of particular concern in high TB burden settings such as Western Cape Province, South Africa. OBJECTIVES: To describe the diagnosis, management and outcome of patients who developed active TB while receiving a bDMARD. RESULTS: Ten patients who screened negative for TB prior to initiation of a bDMARD subsequently developed active TB. TB was diagnosed between 10 months and 9 years from bDMARD initiation, suggesting new infection, and included 6 cases of extrapulmonary TB. All patients required multiple tests to confirm the diagnosis of TB, and all were successfully treated. CONCLUSIONS: TB can occur in patients on bDMARD therapy despite initial screening, and may have unusual, extrapulmonary manifestations that pose a diagnostic challenge.


Assuntos
Antirreumáticos/efeitos adversos , Doenças Reumáticas/tratamento farmacológico , Tuberculose/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Antirreumáticos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , África do Sul , Tuberculose/diagnóstico , Tuberculose/etiologia , Adulto Jovem
3.
Aust Health Rev ; 45(6): 696-703, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34856118

RESUMO

Objective This study examined the content and impact of a new digital communication medium, called a VIDCAST, implemented at a large hospital and health service when the COVID-19 pandemic was announced, and the key concerns held by staff at the time when the health service was preparing for the COVID-19 pandemic to arrive in this health service. Methods A mixed-methods approach was used. Thematic analysis of 20 transcripts of daily VIDCASTS broadcast between 30 March and 24 April 2020 was undertaken, in addition to descriptive analysis of feedback from an anonymous online survey. Results Survey feedback from 322 staff indicated almost universal satisfaction with this new communication method. The VIDCASTS provided a new COVID-safe method for the Executive to connect to staff at a time of uncertainty. Thematic analysis of the content of the VIDCASTS revealed three themes: 'Accurate Information', 'Reassurance and Support' and 'Innovation'. The Executive was able to reassure staff about what the organisation was doing to safeguard the health and wellbeing of all, and enabled an effective response to the pandemic. Conclusions The digital communication channel of VIDCASTS, rapidly operationalised at a major Australian hospital and health service in March 2020, provided important information and support for staff as it prepared for the anticipated COVID-19 surge. What is known about the topic? When the COVID-19 pandemic began, traditional face-to-face staff meetings were disrupted and many hospitals and their staff were left scrambling for information, and for reassurance about their safety, as they prepared to receive increasing numbers of COVID-19 patients. What does this paper add? The implementation of a digital communication tool was able to address many of the concerns raised by hospital staff in other geographic locations dealing with surging COVID-19 cases and underpinned a globally leading COVID-19 response. What are the implications for practitioners? New digitised communication methods provided an effective vehicle to inform and support staff in the early stages of pandemic preparation.


Assuntos
COVID-19 , Pandemias , Austrália/epidemiologia , Comunicação , Humanos , Pandemias/prevenção & controle , SARS-CoV-2
4.
Burns ; 46(8): 1903-1913, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32739223

RESUMO

OBJECTIVE: Compression garments are well accepted as routine practice for scar management after burn. In a recent systematic review, six main reasons for compression garment non-adherence were identified including sensory disturbances. To further understand the impact of sensory issues, the aim of the present study is to investigate associations between sensory variables and compression garment wear. METHOD: Adults (N = 117) attending a quaternary adult burns outpatient clinic completed: The Adolescent/Adult Sensory Profile; a custom-designed compression garment wear questionnaire; and three quantitative sensory testing procedures (Two-Point Discrimination, Mechanical Detection Threshold and Pressure Pain Threshold). RESULTS: Patients who reported lower Pressure Pain Threshold or Mechanical Detection Threshold, higher acuity for Two Point Discrimination, and higher than average sensory avoiding and sensory sensitivity patterns were less adherent with garment wear. CONCLUSIONS: Overall, sensory factors assessed using both self-report and quantitative sensory testing were associated with compression garment adherence. This knowledge suggests the value in developing and evaluating sensory-informed treatment strategies to improve compression garment wear.


Assuntos
Queimaduras/terapia , Transtornos de Sensação/etiologia , Meias de Compressão/normas , Adolescente , Adulto , Idoso , Queimaduras/complicações , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Queensland , Transtornos de Sensação/fisiopatologia , Meias de Compressão/efeitos adversos , Percepção do Tato/fisiologia
5.
Burns ; 46(2): 472-482, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31852617

RESUMO

OBJECTIVE: Up to 40% of adult burn-injured patients are non-adherent with prescribed compression garment wear. The aim of this paper is to systematically review the literature to understand barriers to adherence with compression garment wear. METHOD: Papers were included if they: investigated adults who required compression garment wear for the management of burns scars; focussed on reasons for non-adherence to compression garment wear; and were available in English. The process of meta-ethnography was then followed to synthesise the findings. RESULTS: The factors impacting adherence to compression garment wear were grouped into six themes: sensory factors, psychological state, the impact of the garment on the patient's function, the availability of social support, the degree of choice, and the education provided to patients by their therapists. A model of compression garment adherence was developed detailing how these factors fit within the continuum of treatment for a burn-injured patient. CONCLUSIONS: Adherence to compression garment wear post-burn injury is a complex, dynamic phenomenon impacted by a range of factors. Findings from this review may inform approaches to support more consistent and/or extended garment wear, potentially improving scar outcomes and quality-of-life. Further research is recommended to investigate how each of the six identified themes impact adherence.


Assuntos
Atividades Cotidianas , Queimaduras/terapia , Cicatriz Hipertrófica/prevenção & controle , Vestuário , Bandagens Compressivas , Cooperação do Paciente , Educação de Pacientes como Assunto , Apoio Social , Antropologia Cultural , Ansiedade/psicologia , Imagem Corporal/psicologia , Temperatura Corporal , Comportamento de Escolha , Cicatriz Hipertrófica/terapia , Humanos , Terapeutas Ocupacionais , Terapia Ocupacional , Dor , Fatores de Risco , Autoimagem
6.
S Afr Med J ; 108(4): 325-328, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29629684

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological condition presenting with seizures and visual disturbances and diagnosed on magnetic resonance imaging (MRI). Little is understood about its pathogenesis, particularly in children, but it is thought to be related to hypertension. OBJECTIVES: To review the presentation, diagnosis and outcome of PRES in paediatric renal patients at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, between 1 January 2000 and 31 January 2017 and compare these with published case reports to date. METHODS: This was a retrospective analysis of five new cases and a review of the existing literature. RESULTS: The five reported patients were all hypertensive at the time of diagnosis and presented with seizures. Most (91%) of the 64 reviewed patients were also hypertensive at initial presentation. All five of the reported and 91% of the reviewed patients presented with seizures. The most common pattern of change on MRI occurred in the parietal and occipital regions. Complete neurological recovery occurred in four of the five reported and 87.5% of the reviewed patients. CONCLUSION: All patients presented clinically with hypertensive crises and radiological evidence of PRES. Seizures were the most common presenting symptom. The prognosis for paediatric patients with PRES is favourable, so it is important to confirm the diagnosis in low-resource settings where intensive care is limited.

7.
Ann Thyroid Res ; 4(1): 122-125, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29541701

RESUMO

OBJECTIVES: To evaluate the reliability of normal Thyroid Stimulating Hormone (TSH) as a thyroid function test and assess the effect of Adrenocorticotropic Hormone (ACTH) on serum TSH concentration. DESIGN AND METHODS: Patients presenting to the National Institutes of Health Department of Endocrinology outpatient clinic with symptoms consistent with hypothyroidism were identified. Thyroid hormone concentrations were measured by liquid chromatography/tandem mass spectrometry and immunoassay. Patients with normal TSH concentrations were assessed for both clinical and biochemical hypothyroidism.We evaluated the effect of ACTH stimulation (performed on patients for assessment of adrenal function) on TSH concentration. RESULTS: Patients with symptoms consistent with hypothyroidism but with normal TSH values in the range of 1-4 IU/mL and normal free T4 (FT4) values by immunoassay measurements were confirmed to be biochemically hypothyroid following measurements of thyroid hormones by mass spectrometry. We present case studies of two patients, a 76-year-old male and a 58-year-old female. Improvement in the male patient's hypothyroid symptoms, including afternoon fatigue, constipation, alopecia, dry skin and high cholesterol, was documented after initiating thyroid hormone replacement.ACTH stimulation resulted in an average decrease of 17% in TSH between time 0 and 60 minutes post stimulation. CONCLUSION: Although measurement of TSH is a convenient screen for thyroid function, it is influenced by many factors which may affect its overall reliability. We believe thyroid function should be assessed by more than a single test. We recommend measurement of thyroid hormone concentrations by mass spectrometry if the patient's clinical presentation is discordant with their TSH levels.

8.
Int J Pharm ; 536(1): 370-376, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29197564

RESUMO

Tablets are the most common solid dosage form of pharmaceutical active ingredients due to their ease of use. Their dissolution behaviour depends on the particle size distribution and physicochemical properties of the formulation, and the compression process, which need to be optimised for producing consistently robust tablets, as weaker tablets are often prone to breakage during production, transport and end use. Tablet strength is typically determined by diametric compression and friability tests. The former gives rise to propagation of a crack on a plane along the compression axis, whilst the latter, carried out in a rotating drum, incurs surface damage and produces chips and debris. These tests produce different measures of strength, neither of which have been correlated with mechanical properties that are accountable for breakage, i.e. hardness, elastic modulus and fracture toughness. We propose a new method based on single tablet impact testing, following the work of Ghadiri and Zhang, 2002, who analysed particle damage by propagation of sub-surface lateral cracks and identified the fundamental form accountable for impact surface damage to be a lumped parameter related to hardness and fracture toughness. Microindentation, carried out separately, to determine fracture toughness led to complete failure of the tablets, hence an unreliable measurement of fracture toughness and no correlation with the experimental trend. In addition, by assuming the fracture toughness to be proportional to the square root of Young's modulus, the indentation measurements do not correlate well with the impact breakage. The discrepancy between the impact and indentation methods is expected to be due to mechanical property variation across the tablet surface, and with strain rate. The impact method is a more suitable test to describe tablet propensity for attrition as it directly represents the failure mode tablets may experience during processing under well-defined conditions. In contrast, the friability test subjects tablets to a similar breakage mechanism but under less well-defined conditions, whilst the compression test represents a different failure mode that is not representative of stresses incurred during processing.


Assuntos
Comprimidos/química , Química Farmacêutica/métodos , Módulo de Elasticidade/efeitos dos fármacos , Excipientes/química , Dureza/efeitos dos fármacos , Teste de Materiais/métodos , Pressão , Estresse Mecânico , Propriedades de Superfície/efeitos dos fármacos
9.
Eur J Pain ; 21(1): 82-91, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27301642

RESUMO

BACKGROUND: Establishment of cutpoints for classifying mild, moderate and severe pain is commonly based on single rating of worst or average pain. However, single pain measure may serve as a brief and partial surrogate for composite pain ratings. This study aimed to base composite pain ratings to establish optimal cutpoint that maximized the difference of pain interference on daily function and compare its utility with those based on single worst and average pain. METHODS: Data were from a cohort study of 322 patients with chronic pain. Brief pain inventory (including four items measuring the least, worst, average and current pain) was administered. Rasch analysis and Serlin et al.'s (Pain, 61, 1995, 277) method were used to derive optimal cutpoint. RESULTS: Rasch analysis calibrated the least, worst, average and current pain items into a unidimensional hierarchy and produced composite pain measurement. The optimal cutpoint for composite pain (mild, ≤4; moderate, >4-6; severe, >6-10 on the 0-10 numeric rating scale) differed from those cutpoints for worst (≤6; >6-8; >8-10) and average pain (≤5; >5-7; >7-10). The optimal cutpoint for composite pain was better able than those for worst and average pain to distinguish among groups on patient-rated pain quality and quality of life. The optimal cutpoint for average pain had better discriminant ability than that for worst pain. CONCLUSION: The results suggest that using optimal cutpoint for composite pain may be useful to classify clinically important groups in patients with chronic pain and that average pain may be an alternative choice if a single item is used. WHAT DOES THIS STUDY ADD?: Using composite pain, optimal classification for mild, moderate and severe pain exhibited better discriminant ability than using single worst/average pain. The difficulty hierarchy of the least, worst, average and current pain helps to screen people with irregular responses.


Assuntos
Dor Crônica/classificação , Dor Crônica/diagnóstico , Adulto , Idoso , Dor Crônica/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Qualidade de Vida , Índice de Gravidade de Doença
10.
Eur J Pain ; 20(7): 1044-57, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26688332

RESUMO

BACKGROUND: Endometriosis is a common cause of pain including radicular pain. Ectopic endometrial tissue may directly affect peripheral nerves including the sciatic, which has not been modelled in animals. METHODS: We developed a rat model for sciatic endometriosis by grafting a piece of autologous uterine tissue around the sciatic nerve. Control animals underwent a similar surgery but received a graft of pelvic fat tissue. RESULTS: The uterine grafts survived and developed fluid-filled cysts; the adjacent nerve showed signs of swelling and damage. Mechanical and cold hypersensitivity and allodynia of the ipsilateral hindpaw developed gradually over the first 2 weeks after the surgery, peaked at 2-5 weeks, and was almost resolved by 7 weeks. Control animals showed only minor changes in these pain behaviours. Histological signs of inflammation in the uterine graft and in the adjacent nerve were observed at 3 weeks but were resolving by 7 weeks. In vivo fibre recording showed increased spontaneous activity, especially of C-fibres, in sciatic nerve proximal to the uterine graft. Several pro-inflammatory cytokines including interluekin-18, VEGF, fractalkine, and MIP-1α, were elevated in the uterine graft plus sciatic nerve samples, compared to samples from normal nerve or nerve plus fat graft. Growth associated protein 43 (GAP43), a marker of regenerating nerve fibres, was observed in the adjacent sciatic nerve as well as in the uterine graft. CONCLUSIONS: This model shared many features with other rat models of endometriosis, but also had some unique features more closely related to neuropathic pain models. WHAT DOES THIS STUDY/REVIEW ADD: Some especially painful forms of endometriosis are essentially neuropathic, because peripheral nerves are directly affected by nearby ectopic endometrial tissue. We modelled endometriosis by implanting autologous uterine tissue around rat sciatic nerve. We observed mechanical and cold pain behaviours along with signs of inflammation and nerve damage and increased pro-inflammatory cytokines at the implant site. Pain behaviours correlated with signs of nerve inflammation and damage rather than with cyst survival.


Assuntos
Endometriose/complicações , Hiperalgesia/etiologia , Inflamação/etiologia , Neuralgia/etiologia , Nervo Isquiático/patologia , Animais , Modelos Animais de Doenças , Feminino , Ratos , Ratos Sprague-Dawley
11.
Neuroscience ; 291: 317-30, 2015 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-25686526

RESUMO

In the spinal nerve ligation (SNL) model of neuropathic pain, as in other pain models, abnormal spontaneous activity of myelinated sensory neurons occurs early and is essential for establishing pain behaviors and other pathologies. Sympathetic sprouting into the dorsal root ganglion (DRG) is observed after SNL, and sympathectomy reduces pain behavior. Sprouting and spontaneous activity may be mutually reinforcing: blocking neuronal activity reduces sympathetic sprouting, and sympathetic spouts functionally increase spontaneous activity in vitro. However, most studies in this field have used nonspecific methods to block spontaneous activity, methods that also block evoked and normal activity. In this study, we injected small inhibitory (si) RNA directed against the NaV1.6 sodium channel isoform into the DRG before SNL. This isoform can mediate high-frequency repetitive firing, like that seen in spontaneously active neurons. Local knockdown of NaV1.6 markedly reduced mechanical pain behaviors induced by SNL, reduced sympathetic sprouting into the ligated sensory ganglion, and blocked abnormal spontaneous activity and other measures of hyperexcitability in myelinated neurons in the ligated sensory ganglion. Immunohistochemical experiments showed that sympathetic sprouting preferentially targeted NaV1.6-positive neurons. Under these experimental conditions, NaV1.6 knockdown did not prevent or strongly alter single evoked action potentials, unlike previous less specific methods used to block spontaneous activity. NaV1.6 knockdown also reduced pain behaviors in another pain model, chronic constriction of the sciatic nerve, provided the model was modified so that the lesion site was relatively close to the siRNA-injected lumbar DRGs. The results highlight the relative importance of abnormal spontaneous activity in establishing both pain behaviors and sympathetic sprouting, and suggest that the NaV1.6 isoform may have value as a therapeutic target.


Assuntos
Gânglios Espinais/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.6/metabolismo , Neuralgia/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Potenciais de Ação/fisiologia , Animais , Modelos Animais de Doenças , Feminino , Gânglios Espinais/patologia , Técnicas de Silenciamento de Genes , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Ligadura , Masculino , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/fisiologia , Neuralgia/patologia , RNA Interferente Pequeno , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Células Receptoras Sensoriais/patologia , Caracteres Sexuais , Nervos Espinhais/lesões , Tato
12.
Am J Health Promot ; 29(3): 158-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24460005

RESUMO

PURPOSE: To determine the effect of two jumping programs on hip bone mineral density (BMD) in women. DESIGN: Randomized controlled trial. SETTING: Approximately 20 cities in the Mountain West. SUBJECTS: Sixty premenopausal women, aged 25 to 50 years, completed the intervention. INTERVENTION: Subjects were randomly assigned to a control group or one of two jumping groups. The Jump 10 group performed 10 jumps with 30 seconds rest between jumps, twice daily for 16 weeks, while the Jump 20 group performed the same protocol but with 20 jumps. MEASURES: Hip BMD was measured by using dual-energy x-ray absorptiometry. ANALYSIS: Analysis of variance and covariance. RESULTS: At 8 weeks, unadjusted percentage change in hip BMD was significantly different among groups (F = 5.4, p = .0236). Specifically, compared with controls, the Jump 20 women had significantly greater gains in hip BMD and the Jump 10 women had marginally greater improvements. Following 16 weeks of jumping, differences between the Jump 10 and the Jump 20 groups compared with controls were significant (F = 4.2, p = .0444), especially after adjusting for the covariates (F = 7.3, p = .0092). CONCLUSION: After 16 weeks of high-impact jump training, hip BMD can be improved in premenopausal women by jumping 10 or 20 times, twice daily, with 30 seconds of rest between each jump, compared with controls.


Assuntos
Densidade Óssea/fisiologia , Exercício Físico/fisiologia , Pré-Menopausa/fisiologia , Absorciometria de Fóton , Adulto , Fatores Etários , Peso Corporal , Cálcio da Dieta , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Estados Unidos
13.
Can Commun Dis Rep ; 41(6): 124-131, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29769944

RESUMO

Hantavirus pulmonary syndrome is a disease caused by the inhalation of excreta from infected deer mice. In Canada, the majority of hantavirus pulmonary syndrome cases occur in the western provinces of British Columbia, Alberta, Saskatchewan and Manitoba and the primary cause of the illness is the Sin Nombre virus. Only one case of hantavirus pulmonary syndrome has been documented in eastern Canada (Québec); however, Sin Nombre virus-infected deer mice have been identified across the country. Although cases are rare (yearly case numbers range from zero to 13 and the total number of confirmed cases in Canada now total 109), the mortality rate among infected individuals is approximately 30%. The majority of cases occur in the spring and early summer indicating seasonally-associated risk factors for viral exposure. In 2013 and 2014, a substantial increase in the number of hantavirus pulmonary syndrome cases was identified; however the cause remains unclear. No antivirals or vaccines are currently available and treatment is supportive. Public education, rodent control and the use of personal protective measures are key to avoid infections in at-risk populations.

14.
Work ; 49(3): 455-64, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24004780

RESUMO

BACKGROUND: No self-management interventions have been developed to empower those chronically disabled by a musculoskeletal condition to find and/or remain at work. OBJECTIVE: Developand evaluate the content of two self-management training modules to improve vocational outcomes for those with chronic musculoskeletal disorders. METHODS: Stanford University's Chronic Disease Self-Management Program provided the framework for the new modules. Focus groups with the eightpersons with workdisabilities and concept-mapping sessions with the 12 experienced vocational rehabilitation professionals were conducted to identify factors and themes contributing to workers remaining/returning to work post-injury. Five experienced self-management trainers reviewed the modules for consistency with self-management principles. RESULTS: Two new self-management modules: 'Navigating the System' and 'Managing a Return to Work' were developed.The persons with work disabilitiesgenerated four themes: accepting and coping with injury; skills to manage pain and life; positive working relationships and, re-inventing self, whereas the rehabilitation professionals identified three themes:communication and support of others; the injured worker's abilities and resources, and knowledge and education. CONCLUSIONS: Anintervention developed to enhance self-management skills and facilitate positive vocational outcomes of those seeking to return to work post-injury was confirmed as relevant by persons with work disabilities, rehabilitation professionals and self-management trainers.


Assuntos
Pessoas com Deficiência , Doenças Musculoesqueléticas/fisiopatologia , Recuperação de Função Fisiológica , Retorno ao Trabalho , Autocuidado , Educação Vocacional , Gerenciamento Clínico , Feminino , Grupos Focais , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde
15.
Zoonoses Public Health ; 59 Suppl 2: 151-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22958259

RESUMO

The mobile laboratory provides a safe, rapid and flexible platform to provide effective diagnosis of Ebola virus as well as additional differential diagnostic agents in remote settings of equatorial Africa. During the 2007 Democratic Republic of Congo outbreak of Ebola-Zaire, the mobile laboratory was set up in two different locations by two separate teams within a day of equipment arriving in each location. The first location was in Mweka where our laboratory took over the diagnostic laboratory space of the local hospital, whereas the second location, approximately 50 km south near Kampungu at the epicentre of the outbreak, required local labour to fabricate a tent structure as a suitable pre-existing structure was not available. In both settings, the laboratory was able to quickly set up, providing accurate and efficient molecular diagnostics (within 3 h of receiving samples) for 67 individuals, including four cases of Ebola, seven cases of Shigella and 13 cases of malaria. This rapid turn-around time provides an important role in the support of patient management and epidemiological surveillance.


Assuntos
Doença pelo Vírus Ebola/epidemiologia , Doença pelo Vírus Ebola/terapia , Laboratórios/organização & administração , Animais , Controle de Doenças Transmissíveis , República Democrática do Congo , Reservatórios de Doenças/veterinária , Ebolavirus , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Zoonoses
16.
J Neurophysiol ; 108(5): 1473-83, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22673325

RESUMO

Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR(1)) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. To examine the potential role of S1PR(2) in regulating neuronal excitability we used the established selective antagonist of S1PR(2), JTE-013. Here we report that exposure to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70-80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5'-O-(2-thiodiphosphate) (GDP-ß-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E(2). Pretreatment with pertussis toxin or the selective S1PR(1) antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR(2). In behavioral studies, injection of JTE-013 into the rat's hindpaw produced a significant increase in the mechanical sensitivity in the ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect the withdrawal latency to thermal stimulation. Thus JTE-013 augments neuronal excitability independently of S1PR(2) by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR(1). Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Pirazóis/farmacologia , Piridinas/farmacologia , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Células Receptoras Sensoriais/efeitos dos fármacos , Análise de Variância , Anilidas/farmacologia , Animais , Capsaicina/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Dinoprostona/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Gânglios Espinais/citologia , Guanosina Difosfato/análogos & derivados , Guanosina Difosfato/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Lisofosfolipídeos/farmacologia , Masculino , Melanoma/patologia , Camundongos , Organofosfonatos/farmacologia , Limiar da Dor/efeitos dos fármacos , Técnicas de Patch-Clamp , Toxina Pertussis/farmacologia , Ratos , Ratos Sprague-Dawley , Fármacos do Sistema Sensorial/farmacologia , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Tionucleotídeos/farmacologia , Fatores de Tempo , Cicatrização/efeitos dos fármacos
17.
Neuroscience ; 206: 212-23, 2012 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-22265726

RESUMO

Abnormal spontaneous activity of sensory neurons is observed in many different preclinical pain models, but its basis is not well understood. In this study mechanical and cold hypersensitivity were induced in rats after inflammation of the L5 dorsal root ganglion (DRG), initiated by local application of the immune stimulator zymosan in incomplete Freund's adjuvant. Mechanical hypersensitivity was evident by day 1 and maintained for 2 months. The model also showed reduction of rearing behavior in a novel environment. Microelectrode recordings made in isolated whole DRG on day 3 after inflammation showed a marked increase of spontaneous activity, predominantly with a bursting pattern. The incidence was especially high (44%) in Aαß cells. Spontaneous activity and subthreshold membrane potential oscillations were completely blocked by tetrodotoxin (500 nM) and by riluzole (10 µM), a blocker of persistent sodium currents. In vivo, local perfusion of the inflamed DRG for the first 7 days with riluzole gave long-lasting, dose-dependent reduction in mechanical pain behaviors. Riluzole perfusion did not affect mechanical sensitivity in normal animals. Unmyelinated C cells had a very low incidence of spontaneous activity and were much less affected by riluzole in vitro. Taken together these results suggest that high-frequency and/or bursting spontaneous activity in Aαß sensory neurons may play important roles in initiating pain behaviors resulting from inflammatory irritation of the DRG.


Assuntos
Gânglios Sensitivos/fisiologia , Inflamação/fisiopatologia , Fibras Nervosas Mielinizadas/fisiologia , Dor/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Adjuvantes Imunológicos/toxicidade , Animais , Comportamento Animal/fisiologia , Adjuvante de Freund/toxicidade , Gânglios Espinais/fisiologia , Inflamação/induzido quimicamente , Masculino , Potenciais da Membrana/fisiologia , Ratos , Ratos Sprague-Dawley , Zimosan/toxicidade
18.
J Inorg Biochem ; 105(12): 1580-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22071082

RESUMO

Terbium-sensitized luminescence and its applicability towards the detection of Bacillus spores such as anthrax are of significant interest to research in biodefense and medical diagnostics. Accordingly, we have measured the effects of terbium chelation upon the parameters associated with dipicolinate ligation and spore detection. Namely, the dissociation constants, intrinsic brightness, luminescent lifetimes, and biological stabilities for several Tb(chelate)(dipicolinate)(x) complexes were determined using linear, cyclic, and aromatic chelators of differing structure and coordination number. This included the chelator array of NTA, BisTris, EGTA, EDTA, BAPTA, DO2A, DTPA, DO3A, and DOTA (respectively, 2,2',2″-nitrilotriacetic acid; 2,2-bis(hydroxymethyl)-2,2',2″-nitrilotriethanol; ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid; ethylenediamine-N,N,N',N'-tetraacetic acid; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid; diethylenetriamine-N,N,N',N″,N″-pentaacetic acid; 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Our study has revealed that the thermodynamic and temporal emission stabilities of the Tb(chelate)(dipicolinate)(x) complexes are directly related to chelate rigidity and a ligand stoichiometry of x=1, and that chelators possessing either aromaticity or low coordination numbers are destabilizing to the complexes when in extracts of an extremotolerant Bacillus spore. Together, our results demonstrate that both Tb(EDTA) and Tb(DO2A) are chemically and biochemically stable and thus applicable as respectively low and high-cost luminescent reporters for spore detection, and thereby of significance to institutions with developing biodefense programs.


Assuntos
Bacillus/fisiologia , Quelantes/química , Complexos de Coordenação/química , Substâncias Luminescentes/química , Ácidos Picolínicos/química , Térbio/química , Complexos de Coordenação/síntese química , Indicadores e Reagentes/síntese química , Indicadores e Reagentes/química , Cinética , Substâncias Luminescentes/síntese química , Análise de Regressão , Esporos Bacterianos , Relação Estrutura-Atividade , Titulometria
20.
Optometry ; 82(3): 166-74, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21147552

RESUMO

BACKGROUND: While information technology (IT) is playing an increasing role in the delivery of optometric services, little specific information is available about how IT is changing the practice of optometry in Canada or whether optometry schools are adequately preparing their students to use this technology when they graduate. METHODS: Quantitative data on how IT is being used, as well as related barriers and potential benefits, were obtained in a survey of Canadian optometrists (N = 474). Three site visits were made to geographically dispersed Canadian optometry practices identified as exemplars of IT adoption. RESULTS: More than 96% of Canadian optometrists use computers in their practices, but fewer have integrated computers into their examination rooms. Optometrists are regularly using computers to manage their practices and medical record keeping. The automated perimeter is the clinical assessment technology most used (88.4%), followed by the autorefractor (83.9%) and the autokeratometer (72.2%). The anterior segment camera is the technology most likely to be acquired within the next 5 years (36.9%), followed by the scanning laser ophthalmoscope (26.8%). Major benefits of IT for optometrists include being better able to provide patients with images and information to explain results and to inspire greater patient confidence that the practice is state of the art. Perceived barriers include the need for frequent updates, lack of resources for training, and cost. There is support for increased exposure to IT as part of training in optometry. CONCLUSIONS: Use of IT in optometry practices is widespread and likely to continue to increase in the years ahead. IT may be a key element in the future success of optometry practices in an increasingly competitive marketplace. Perceptions of high investment and training costs are barriers to further adoption. Optometrists may benefit from increased exposure to IT as part of their training.


Assuntos
Informática Médica , Optometria , Prática Profissional , Canadá , Computadores/estatística & dados numéricos , Topografia da Córnea , Custos e Análise de Custo , Registros Eletrônicos de Saúde , Humanos , Informática Médica/economia , Informática Médica/educação , Informática Médica/estatística & dados numéricos , Optometria/educação , Optometria/estatística & dados numéricos , Gerenciamento da Prática Profissional/estatística & dados numéricos , Prática Profissional/estatística & dados numéricos , Refratometria , Testes de Campo Visual
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