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1.
Ann Oncol ; 35(2): 221-228, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072158

RESUMO

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.


Assuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Proteínas Hedgehog , Ligantes , Antineoplásicos/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/induzido quimicamente , Progressão da Doença , Amidas/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
2.
Tech Coloproctol ; 25(4): 359-369, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33599902

RESUMO

BACKGROUND: Crohn's anal fistula is a challenging condition, and may require multiple surgical procedures. To replicate successful procedures, these must be adequately reported in the literature. The aim of this study was to review the quality of reporting of components of surgical interventions for Crohn's anal fistula. METHODS: A systematic review was conducted. It was registered with PROSPERO (CRD:42019135157). The Medline and EMBASE databases were searched for studies reporting interventions intended to close fistula in patients with Crohn's disease, published between 1999 and August 2019. Abstracts and full texts were screened for inclusion by two reviewers. Dual extraction of data was performed to compare reporting to the TIDiER and Blencowe frameworks for reporting of interventions. RESULTS: Initial searches identified 207 unique studies; 38 full texts were screened for inclusion and 33 were included. The most common study design was retrospective cohort (17/33), and the most frequently reported interventions were anal fistula plug (n = 8) and fibrin glue (n = 6). No studies showed coverage of all domains of TIDieR. Reporting was poor among domains related to who provided an intervention, where it was provided, and how it was tailored. Reporting of domains in the Blencowe framework was poor; the majority of studies did not report the component steps of procedures or efforts to standardise them. CONCLUSIONS: This study demonstrates that reporting on technical aspects of interventions for Crohn's anal fistula is poor. Surgeons should aim to improve reporting to allow accurate reproduction of techniques both in clinical practice and in clinical trials.


Assuntos
Doença de Crohn , Procedimentos Cirúrgicos do Sistema Digestório , Fístula Retal , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Humanos , Fístula Retal/etiologia , Fístula Retal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
3.
Diabet Med ; 38(5): e14430, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33073393

RESUMO

AIMS: Sustained engagement in type 1 diabetes self-management behaviours is a critical element in achieving improvements in glycated haemoglobin (HbA1c) and minimising risk of complications. Evaluations of self-management programmes, such as Dose Adjustment for Normal Eating (DAFNE), typically find that initial improvements are rarely sustained beyond 12 months. This study identified behaviours involved in sustained type 1 diabetes self-management, their influences and relationships to each other. METHODS: A mixed-methods study was conducted following the first two steps of the Behaviour Change Wheel framework. First, an expert stakeholder consultation identified behaviours involved in self-management of type 1 diabetes. Second, three evidence sources (systematic review, healthcare provider-generated 'red flags' and participant-generated 'frequently asked questions') were analysed to identify and synthesise modifiable barriers and enablers to sustained self-management. These were characterised according to the Capability-Opportunity-Motivation-Behaviour (COM-B) model. RESULTS: 150 distinct behaviours were identified and organised into three self-regulatory behavioural cycles, reflecting different temporal and situational aspects of diabetes self-management: Routine (e.g. checking blood glucose), Reactive (e.g. treating hypoglycaemia) and Reflective (e.g. reviewing blood glucose data to identify patterns). Thirty-four barriers and five enablers were identified: 10 relating to Capability, 20 to Opportunity and nine to Motivation. CONCLUSIONS: Multiple behaviours within three self-management cycles are involved in sustained type 1 diabetes self-management. There are a wide range of barriers and enablers that should be addressed to support self-management behaviours and improve clinical outcomes. The present study provides an evidence base for refining and developing type 1 diabetes self-management programmes.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Motivação/fisiologia , Autogestão , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Prova Pericial/estatística & dados numéricos , Comportamentos Relacionados com a Saúde/fisiologia , Humanos , Defesa do Paciente/estatística & dados numéricos , Sistemas de Apoio Psicossocial , Autogestão/métodos , Autogestão/psicologia , Autogestão/estatística & dados numéricos , Comportamento Social , Revisões Sistemáticas como Assunto , Reino Unido/epidemiologia
5.
Clin Exp Immunol ; 182(3): 289-301, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26332605

RESUMO

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing HIV-1 monoclonal antibody (mAb) isolated from the B cells of an HIV-infected patient. It is directed against the HIV-1 CD4 binding site and is capable of potently neutralizing the majority of diverse HIV-1 strains. This Phase I dose-escalation study in healthy adults was conducted at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Primary objectives were the safety, tolerability and pharmacokinetics (PK) of VRC01 intravenous (i.v.) infusion at 5, 20 or 40 mg/kg, given either once (20 mg/kg) or twice 28 days apart (all doses), and of subcutaneous (s.c.) delivery at 5 mg/kg compared to s.c. placebo given twice, 28 days apart. Cumulatively, 28 subjects received 43 VRC01 and nine received placebo administrations. There were no serious adverse events or dose-limiting toxicities. Mean 28-day serum trough concentrations after the first infusion were 35 and 57 µg/ml for groups infused with 20 mg/kg (n = 8) and 40 mg/kg (n = 5) doses, respectively. Mean 28-day trough concentrations after the second infusion were 56 and 89 µg/ml for the same two doses. Over the 5-40 mg/kg i.v. dose range (n = 18), the clearance was 0.016 l/h and terminal half-life was 15 days. After infusion VRC01 retained expected neutralizing activity in serum, and anti-VRC01 antibody responses were not detected. The human monoclonal antibody (mAb) VRC01 was well tolerated when delivered i.v. or s.c. The mAb demonstrated expected half-life and pharmacokinetics for a human immunoglobulin G. The safety and PK results support and inform VRC01 dosing schedules for planning HIV-1 prevention efficacy studies.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/efeitos adversos , Anticorpos Amplamente Neutralizantes , Relação Dose-Resposta a Droga , Feminino , Anticorpos Anti-HIV/administração & dosagem , Anticorpos Anti-HIV/efeitos adversos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade
6.
Clin Exp Dermatol ; 39(5): 616-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24934914

RESUMO

Naevus spilus (NS) is a naevoid disorder characterized by hyperpigmented macules or papules scattered over a café-au-lait macule. Such café-au-lait macules are often present at birth, and the darker pigmented speckles of NS slowly increase in number and size over a period of several years. NS can therefore be difficult to evaluate clinically for the development of melanoma. In vivo confocal microscopy (IVCM) is a novel method that allows examination at cellular resolution of cutaneous lesions in vivo. IVCM has been shown to have twice the specificity of dermoscopy for the diagnosis of melanoma, with comparable sensitivity. It has been shown to be useful in the detection and grading of dysplastic naevi, which are recognized precursors of melanoma in some cases. In this report, we highlight that IVCM can also be used as a tool complementary to dermoscopy to identify areas of dynamic change in clinically and dermoscopically equivocal lesions. IVCM may thereby assist in the early detection of melanocytic atypia and melanoma arising in NS, in turn leading to excision of melanoma at an early stage, which is associated with a favourable outcome. We also outline some of the difficulties encountered in confocal microscopy and histology when differentiating melanoma from dysplastic naevi.


Assuntos
Dermatoses da Perna/patologia , Microscopia Confocal , Nevo Pigmentado/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Coxa da Perna
7.
Chem Senses ; 38(9): 769-81, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24122319

RESUMO

The main olfactory system of mice contains a small subset of olfactory sensory neurons (OSNs) that are stimulated by CO2. The objective of this study was to record olfactory receptor responses to a range of CO2 concentrations to further elucidate steps in the proposed CO2 transduction pathway in mice. Electro-olfactograms (EOGs) were recorded before and after inhibiting specific steps in the CO2 transduction pathway with topically applied inhibitors. Inhibition of extracellular carbonic anhydrase (CA) did not significantly affect EOG responses to CO2 but did decrease EOG responses to several control odorants. Inhibition of intracellular CA or cyclic nucleotide-gated channels attenuated EOG responses to CO2, confirming the role of these components in CO2 sensing in mice. We also show that, like canonical OSNs, CO2-sensitive OSNs depend on Ca²âº-activated Cl⁻ channels for depolarization of receptor neurons. Lastly, we found that guanylyl cyclase-D knockout mice were still able to respond to CO2, indicating that other pathways may exist for the detection of low concentrations of nasal CO2. We discuss these findings as they relate to previous studies on CO2-sensitive OSNs in mice and other animals.


Assuntos
Dióxido de Carbono/farmacologia , Guanilato Ciclase/genética , Mucosa Nasal/efeitos dos fármacos , Receptores de Superfície Celular/genética , Animais , Canais de Cloreto/metabolismo , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Fenômenos Eletrofisiológicos , Feminino , Guanilato Ciclase/deficiência , Guanilato Ciclase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucosa Nasal/fisiologia , Neurônios Receptores Olfatórios/metabolismo , Pentanóis/farmacologia , Receptores de Superfície Celular/deficiência , Receptores de Superfície Celular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Olfato/fisiologia
8.
Aust Dent J ; 58(1): 18-25, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23441788

RESUMO

BACKGROUND: A study undertaken in 1992-1993 identified that HIV-infected dental patients were substantially disadvantaged with regard to the social impact of their oral disease. The oral pain experienced by HIV-positive patients prior to the introduction of combination antiretroviral therapy (cART) was attributable to specific features of HIV-related periodontal disease and other oral manifestations of HIV such as candida infections and xerostomia. A repeat of this study in 2009-2010 provided additional information in the post-cART era. METHODS: Data were collected from three sources: the 2009-2010 HIV-positive sample, the National Survey of Adult Oral Health (NSAOH) and the original 1992-1993 study. Collation of data was by clinical and radiographic oral examination. Information about the social impact of oral conditions was obtained from the Oral Health Impact Profile. RESULTS: The caries experience of the 2009-2010 HIV-positive sample was improved with statistical significance for both mean DMFT and mean DT, while the presence of HIV-related periodontal disease still occurs. Statistically significant improvements were achieved for prevalence and severity of oral health related quality of life. CONCLUSIONS: The need for timely access to oral health care with a focus on prevention is essential for HIV-positive individuals whose health is impacted by chronic disease, smoking and salivary hypofunction.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , Soropositividade para HIV/complicações , Doenças da Boca/virologia , Saúde Bucal , Adulto , Antirretrovirais/uso terapêutico , Estudos Transversais , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , Necessidades e Demandas de Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/prevenção & controle , Dor/virologia , Doenças Periodontais/epidemiologia , Doenças Periodontais/prevenção & controle , Doenças Periodontais/virologia , Prevalência , Qualidade de Vida , Fumar/efeitos adversos , Austrália do Sul/epidemiologia , Xerostomia/complicações , Adulto Jovem
9.
Int J Immunogenet ; 40(4): 311-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23280011

RESUMO

Hypersensitivity reactions to the drug abacavir, used to treat HIV/AIDS patients, is associated with possession of HLA-B*57:01. We have carefully assessed two commercially available HLA-B57/B58 murine monoclonal antibodies [0196HA and BIH0243 (One Lambda Inc.)] in a simple flow cytometry-based assay. The evaluation involved tests on 228 reference and random samples covering 91% of all WHO recognized HLA-A, B and C specificities. These involved donors with six different HLA-B*57 alleles and included 19 examples of B*57:01. Both antibodies unambiguously detected B57, but there were small difference in their reactivity against B57-positive non-B*57:01 samples. Importantly, there was no reactivity against B57/B58-negative samples. The possible amino acid motifs involved in the reactivity of these antibodies with B57/B58 were delineated. Thus, HLA-B57/B58, normally present in <10% of patients, can be easily recognized using these two antibodies and further tested by a DNA-based typing method to identify B*57:01.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Anticorpos Monoclonais/imunologia , Didesoxinucleosídeos/efeitos adversos , Hipersensibilidade a Drogas/prevenção & controle , Antígenos HLA-B/análise , Alelos , Fármacos Anti-HIV/uso terapêutico , Didesoxinucleosídeos/uso terapêutico , Hipersensibilidade a Drogas/genética , Hipersensibilidade a Drogas/imunologia , Prescrições de Medicamentos , Epitopos/genética , Citometria de Fluxo , Variação Genética , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Humanos
10.
Aust Dent J ; 57(4): 470-6; quiz 518, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23186573

RESUMO

BACKGROUND: The introduction of combination antiretroviral therapy (cART) for the treatment of human immunodeficiency virus (HIV) has resulted in changes to the oral health of infected individuals. Little data are available describing prevalence and severity of oral manifestations in a post cART cohort of HIV positive patients. METHODS: A retrospective case note analysis was performed at the Special Needs Unit (SNU), Adelaide Dental Hospital with emphasis on identifying the prevalence of HIV related oral manifestations (OM). A total of 498 (474 males: 24 females) HIV positive individuals were identified who had attended SNU for dental care between 2001 and 2008. RESULTS: There were significant differences observed in the prevalence of oral manifestations between cART and non-cART groups, and also in comparison to a previous pilot study. Individuals taking cART therapy tended to present with more evidence of linear gingival erythema, angular cheilitis, human papilloma virus associated squamous papillomas and xerostomia. CONCLUSIONS: The widespread adoption of cART in the treatment of HIV has altered the oral health profile of these individuals. These findings provide information on the incidence of oral conditions and demonstrate the need to identify and address oral health needs for people living with HIV.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Doenças da Boca/epidemiologia , Saúde Bucal , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Austrália , Queilite/epidemiologia , Feminino , Doenças da Gengiva/complicações , Doenças da Gengiva/epidemiologia , Infecções por HIV/epidemiologia , Soropositividade para HIV/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Estudos Retrospectivos
11.
Transplant Proc ; 40(6): 1839-43, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18675065

RESUMO

Pretransplantation crossmatching is an integral part of kidney transplantation. Flow cytometric crossmatch (FCXM) is more sensitive than complement-dependent cytotoxic crossmatch (CDC-XM). However, the clinical significance of positive FCXM with negative CDC-XM is controversial. We evaluated FCXM in 455 consecutive deceased donor renal transplants. All had a negative CDC-XM. There were 341 T-cell and B-cell FCXM negative and 38 T-cell and B-cell positive. There was a higher percentage of retransplantations and HLA mismatches (26.3% vs 8.2%, P= .002 and 2.45 vs 1.99, P= .02, respectively) in the FCXM-positive group compared with the FCXM-negative group; 65.8% of the FCXM-positive patients had rejection compared with 49.3% of the FCXM-negative patients (odds ratio [OR]=1.89, P= .06). FCXM-positive patients had a higher incidence of vascular rejection (28.9% vs 12.6%, OR=2.68, P= .008). One- and 5-year graft survivals were 84% and 66% in the FCXM-positive group vs 90% and 75% in the FCXM-negative group. Censoring for patient death, 1- and 5-year graft survivals were 84% and 73% in the FCXM-positive group vs 94% and 82% in the FCXM-negative group. There was no difference in renal function between the 2 groups. In conclusion, a positive T-cell and B-cell FCXM transplant with a negative CDC-XM is associated with a higher incidence of rejection, twice the risk of vascular rejection, and a trend toward poorer graft survival.


Assuntos
Teste de Histocompatibilidade/métodos , Transplante de Rim/imunologia , Doadores de Tecidos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Citometria de Fluxo/métodos , Antígenos HLA/imunologia , Humanos , Imunoglobulinas/imunologia , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Sensibilidade e Especificidade , Resultado do Tratamento
12.
J Perinatol ; 28(10): 675-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18580880

RESUMO

UNLABELLED: Term and near-term infants with pulmonary hypertension are frequently treated with inhaled nitric oxide. This therapy can be delivered with high-frequency ventilation, but there has been limited study of the relative effectiveness of high-frequency jet ventilation and high-frequency oscillatory ventilation. OBJECTIVE: To compare short-term clinical outcomes of neonates with pulmonary hypertension treated with inhaled nitric oxide plus either high-frequency jet ventilation or high-frequency oscillatory ventilation. STUDY DESIGN: Study infants met the following criteria: >or=35 weeks gestation, respiratory failure with pulmonary hypertension, no congenital malformations and treatment in the first week of life with inhaled nitric oxide plus either high-frequency jet ventilation (n=22) or high-frequency oscillatory ventilation (n=43). Data were collected from medical records. RESULT: The jet ventilation and oscillatory ventilation groups were similar in terms of gestational age, but the jet ventilation group had less severe respiratory illness (that is, lower oxygenation index) just prior to initiation of the combination of nitric oxide and high-frequency ventilation. The jet ventilation group spent more hours on inhaled nitric oxide (71.4 versus 40.8; P=0.004) but was less likely to require extracorporeal membrane oxygenation (2(9%) versus 19(44%); P=0.004). No difference was found in the ages at which oxygen and high-frequency ventilation were discontinued. CONCLUSION: Term and near-term neonates with pulmonary hypertension who require nitric oxide have similar short-term outcomes regardless of whether nitric oxide is delivered by high-frequency jet ventilation or high-frequency oscillatory ventilation.


Assuntos
Fatores Relaxantes Dependentes do Endotélio/administração & dosagem , Ventilação em Jatos de Alta Frequência , Óxido Nítrico/administração & dosagem , Síndrome da Persistência do Padrão de Circulação Fetal/terapia , Administração por Inalação , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento
13.
Chem Senses ; 32(3): 263-71, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17215338

RESUMO

Previous studies indicate that Long-Evans rats can be operantly trained to discriminate inspired CO(2) concentrations as low as 0.5%. This ability has been proposed to be due to the presence of CO(2)-sensitive olfactory receptors that contain the enzyme carbonic anhydrase (CA). The objectives of the present study were as follows: 1) to determine whether Zucker rats could be operantly conditioned to discriminate low concentrations of CO(2) from control air and 2) to determine the rats' CO(2) detection thresholds before and after nasal perfusion of mammalian Ringers or methazolamide, a CA inhibitor. Rats were operantly trained to discriminate between 25% CO(2) and control air (0% CO(2)) and were then subjected to various CO(2) concentrations (0.5-12.5%) to determine their CO(2) detection thresholds. The average (+/-standard error of mean) baseline CO(2) detection threshold of 7 Zucker rats was 0.48 +/- 0.07% CO(2), whereas the average CO(2) detection thresholds after nasal perfusion of either mammalian Ringers or 10(-2) M methazolamide were 1.41 +/- 0.30% and 5.92 +/- 0.70% CO(2), respectively. The average CO(2) detection threshold after methazolamide was significantly greater (P<0.0001) than the baseline detection threshold. These findings demonstrate that like Long-Evans rats, Zucker rats can be trained to discriminate low concentrations of CO(2) and that inhibition of nasal CA reduces the ability of the rats to detect low concentrations (3.5% and below) but not higher concentrations of CO(2) (12.5%). These results add to the growing evidence that olfactory neurons exhibiting CA activity are CO(2) chemoreceptors sensitive to physiological concentrations of CO(2).


Assuntos
Dióxido de Carbono/fisiologia , Inibidores da Anidrase Carbônica/administração & dosagem , Anidrases Carbônicas/efeitos dos fármacos , Cavidade Nasal/efeitos dos fármacos , Limiar Sensorial/fisiologia , Administração Tópica , Animais , Anidrases Carbônicas/metabolismo , Células Quimiorreceptoras/efeitos dos fármacos , Células Quimiorreceptoras/metabolismo , Condicionamento Operante , Feminino , Masculino , Metazolamida/farmacologia , Nervo Olfatório/efeitos dos fármacos , Nervo Olfatório/metabolismo , Ratos , Ratos Zucker , Limiar Sensorial/efeitos dos fármacos
14.
Genet Test ; 10(2): 98-103, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16792512

RESUMO

We designed a set of 35 polymerase chain reaction sequence-specific primers (PCR-SSP) in 29 SSP mixtures to assign 29 HLA-B*27 4-digit level alleles (B*2701-B*2721 and B*2723-B*2730). This was used in conjunction with our 41 PCR-SSP primer mixture low-resolution HLA-B typing set to fully differentiate B*27 from all other HLA-B alleles. Successful typing set validation used 521 B*27 samples covering 13 (B*2701-B*2710 and B*2712, B*2717, B*2723) alleles. The distribution of B*27 alleles was determined in a random population of 4020 local blood donors and the use of PCR-SSP B*27 typing in our routine flow cytometry-based HLA-B27/B2708 typing strategy is described.


Assuntos
Primers do DNA , Sondas de DNA de HLA , Antígeno HLA-B27/genética , Reação em Cadeia da Polimerase/métodos , Alelos , Citometria de Fluxo , Triagem de Portadores Genéticos/métodos , Genótipo , Humanos , Sensibilidade e Especificidade
15.
Eur J Immunogenet ; 30(4): 271-4, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12919288

RESUMO

We evaluated the HLA-B27 typing reagent Com-B27, which is claimed to show minimal cross-reactivity with HLA-B7, for use in flow cytometry-based typing. This combination reagent consists of the fluorescein-conjugated HLA-B27 mouse monoclonal antibody ABC-m3 and a non-conjugated HLA-B7 monoclonal antibody that is claimed to block the reactivity of ABC-m3 to B7 without affecting its reactivity to B27. It reacted well with B27 (B*2702, B*2705) and B2708 [mean median channel fluorescence intensity (MCFI) 8.40] and weakly with B7 (including cells from homozygous B*07 donors), B42/B73 and B22/B37/B44 reference cells (mean MCFI 2.05, 3.09 and 1.10, respectively). It showed a uniform discrimination between B7 and B27/B2708 with no 'overlap' in MCFI values, which was seen with the standard ABC-m3 antibody. There was complete agreement when our standard three-antibody-based B27/B2708 flow cytometry assay and the Com-B27 reagent alone were used to independently assign B27/B2708 status to 651 random patients. Thus, the Com-B27 reagent provided improved discrimination between B7 and B27/B2708 over the ABC-m3 antibody, and its B27/B2708 assignments were comparable with our standard flow cytometry assay. However, for consistently reliable B27/B2708 typing we continue to recommend the use of a minimum of two B27 reagents in a protocol that includes DNA-based testing of 'equivocal' B27/B2708 assignments.


Assuntos
Anticorpos/imunologia , Fluoresceína , Antígeno HLA-B27/análise , Coloração e Rotulagem , Animais , Antígeno HLA-B27/imunologia , Humanos , Camundongos
16.
J Appl Physiol (1985) ; 94(3): 1204-12, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12571143

RESUMO

Central CO(2) chemoreception and the role of carbonic anhydrase were assessed in brain stems from Rana catesbeiana tadpoles and frogs. Buccal and lung rhythms were recorded from cranial nerve VII and spinal nerve II during normocapnia and hypercapnia before and after treatment with 25 microM acetazolamide. The lung response to acetazolamide mimicked the hypercapnic response in early-stage and midstage metamorphic tadpoles and frogs. In late-stage tadpoles, acetazolamide actually inhibited hypercapnic responses. Acetazolamide and hypercapnia decreased the buccal frequency but had no effect on the buccal duty cycle. Carbonic anhydrase activity was present in the brain stem in every developmental stage. Thus more frequent lung ventilation and concomitantly less frequent buccal ventilation comprised the hypercapnic response, but the response to acetazolamide was not consistent during metamorphosis. Therefore, acetazolamide is not a useful tool for central CO(2) chemoreceptor studies in this species. The reversal of the effect of acetazolamide in late-stage metamorphosis may reflect reorganization of central chemosensory processes during the final transition from aquatic to aerial respiration.


Assuntos
Acetazolamida/farmacologia , Dióxido de Carbono/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Células Quimiorreceptoras/fisiologia , Animais , Anidrases Carbônicas/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Nervos Cranianos/fisiologia , Eletrofisiologia , Feminino , Brânquias/fisiologia , Larva , Pulmão/crescimento & desenvolvimento , Pulmão/fisiologia , Masculino , Metamorfose Biológica , Rana catesbeiana , Mecânica Respiratória/efeitos dos fármacos , Estimulação Química
17.
Aust Dent J ; 48(4): 255-8, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14738129

RESUMO

BACKGROUND: The risk of post-extraction complications is higher in patients who are immunosuppressed compared to other patients with normal immune function. In addition, invasive dental procedures are more likely to have serious complications in these patients. This case report demonstrates an effective non-surgical procedure to treat an oro-antral fistula in an HIV-infected man. METHODS: The oro-antral fistula was de-epithelialized under local anaesthesia and the patient wore a surgical splint continuously, removing it only for cleaning, for an eight week period. Chlorhexidine gel was regularly applied to the fitting surface of the splint and the oro-antral communication. The patient was reviewed on a regular basis. RESULTS: This procedure resulted in resolution of the patient's symptoms within two weeks. Complete healing of the oro-antral fistula was evident following eight weeks of wearing the surgical splint. CONCLUSIONS: This procedure provided an effective method of treating an oro-antral fistula in an immunocompromised patient without causing any detrimental effects to the patient's overall health. Adequate pre-surgical assessment of patients prior to extractions is important in all patients to help prevent the occurrence of such complications.


Assuntos
Anti-Infecciosos Locais/administração & dosagem , Clorexidina/administração & dosagem , Assistência Odontológica para Doentes Crônicos/métodos , Infecções por HIV , Fístula Bucoantral/tratamento farmacológico , Adulto , Humanos , Hospedeiro Imunocomprometido , Masculino , Contenções Periodontais
18.
Respir Physiol ; 129(1-2): 219-29, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11738656

RESUMO

Amphibians and reptiles possess CO(2)-sensitive olfactory receptors that cause a dose-dependent decrease in breathing when stimulated by CO(2) concentrations ranging from 0.5 to 8%. In amphibians, it has been shown that inhibition of the enzyme, carbonic anhydrase (CA), attenuates the response of CO(2)-sensitive olfactory receptors to transient changes in nasal CO(2). Histology and electrophysiology studies in frogs show that identification of sites of CA activity can serve as markers for locations of CO(2) chemosensitivity in the olfactory epithelium. There is also growing evidence that CO(2) receptors may be present in the olfactory epithelium of mammals. The objectives of this review are to, (1) summarize the current state of knowledge of olfactory CO(2) receptors in amphibians, reptiles, and mammals; (2) present results from an experiment designed to determine the distribution and density of CA activity within the rat nasal cavity; (3) show results from an experiment that recorded the olfactory receptor response to CO(2) in areas of the rat nasal cavity exhibiting the highest densities of CA activity; and (4) discuss the presumed role of the olfactory CO(2) receptors in the control of breathing and in abnormalities of breathing, such as sudden infant death syndrome (SIDS).


Assuntos
Dióxido de Carbono , Células Quimiorreceptoras/fisiologia , Condutos Olfatórios/fisiologia , Animais , Dióxido de Carbono/farmacologia , Anidrases Carbônicas/metabolismo , Eletrofisiologia , Humanos , Recém-Nascido , Respiração/efeitos dos fármacos , Morte Súbita do Lactente
19.
Mol Microbiol ; 41(6): 1349-56, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11580839

RESUMO

Enterococcus faecium strain 9631355 was isolated from animal sources on the basis of its resistance to the growth promotant avilamycin. The strain also exhibited high-level resistance to evernimicin, a drug undergoing evaluation as a therapeutic agent in humans. Ribosomes from strain 9631355 exhibited a dramatic reduction in evernimicin binding, shown by both cell-free translation assays and direct-binding assays. The resistance determinant was cloned from strain 9631355; sequence alignments suggested it was a methyltransferase and therefore it was designated emtA for evernimicin methyltransferase. Evernimicin resistance was transmissible and emtA was localized to a plasmid-borne insertion element. Purified EmtA methylated 50S subunits from an evernimicin-sensitive strain 30-fold more efficiently than those from a resistant strain. Reverse transcription identified a pause site that was unique to the 23S rRNA extracted from resistant ribosomes. The pause corresponded to methylation of residue G2470 (Escherichia coli numbering). RNA footprinting revealed that G2470 is located within the evernimicin-binding site on the ribosome, thus providing an explanation for the reduced binding of the drug to methylated ribosomes.


Assuntos
Aminoglicosídeos , Antibacterianos/farmacologia , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/enzimologia , Metiltransferases/metabolismo , Animais , Antibacterianos/metabolismo , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Elementos de DNA Transponíveis/genética , DNA Bacteriano/genética , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana/fisiologia , Enterococcus faecium/genética , Genes Bacterianos , Humanos , Metiltransferases/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Plasmídeos/genética , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Ribossômico/química , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribossomos/metabolismo
20.
Aust Dent J ; 46(2): 108-13, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11491226

RESUMO

BACKGROUND: The features of oral hairy leukoplakia (OHL) have been widely reported in the literature. However, no studies have described this lesion in the Australian setting. This study retrospectively examines, with respect to specific clinical factors, the prevalence of OHL in a South Australian HIV-infected population. METHODS: Clinical data were collected from the records of 197 HIV-infected patients who had attended the Adelaide Dental Hospital between January 1986 and February 1995. Data were analysed using the chi-square test. RESULTS: The prevalence of OHL in South Australian HIV-infected patients was 45.2 per cent. The study found the presence of OHL was not related to CD4+ T-lymphocyte count or AIDS-defining illness nor did the length of time a patient had been infected with HIV relate to the presence of OHL. An association was observed between a reduced prevalence of OHL in patients who were taking antiviral medication. CONCLUSION: The prevalence of OHL in South Australia is comparable with results of other studies. This study supports the notion that OHL is not an indicator of immunosuppression in South Australian HIV-infected patients. Further longitudinal studies are required to ascertain the relationship of OHL to HIV disease progression.


Assuntos
Leucoplasia Pilosa/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome de Imunodeficiência Adquirida/epidemiologia , Aciclovir/uso terapêutico , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Antivirais/uso terapêutico , Contagem de Linfócito CD4 , Distribuição de Qui-Quadrado , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Austrália do Sul/epidemiologia , Fatores de Tempo , Zidovudina/uso terapêutico
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