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1.
Trials ; 24(1): 303, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37127683

RESUMO

BACKGROUND: The purpose of this randomized trial is to evaluate the early removal of postoperative drains after robot-assisted minimally invasive oesophagectomy (RAMIE). Evidence is lacking about feasibility, associated pain, recovery, and morbidity. METHODS/DESIGN: This is a randomized controlled multicentric trial involving 72 patients undergoing RAMIE. Patients will be allocated into two groups. The "intervention" group consists of 36 patients. In this group, abdominal and chest drains are removed 3 h after the end of surgery in the absence of contraindications. The control group consists of 36 patients with conventional chest drain management. These drains are removed during the further postoperative course according to a standard algorithm. The primary objective is to investigate whether postoperative pain measured by NRS on the second postoperative day can be significantly reduced in the intervention group. Secondary endpoints are the intensity of pain during the first week, analgesic use, number of postoperative chest X-ray and CT scans, interventions, postoperative mobilization (steps per day as measured with an activity tracker), postoperative morbidity and mortality. DISCUSSION: Until now, there have been no trials investigating different intraoperative chest drain strategies in patients undergoing RAMIE for oesophageal cancer with regard to perioperative complications until discharge. Minimally invasive approaches combined with enhanced recovery after surgery (ERAS) protocols lower morbidity but still include the insertion of chest drains. Reduction and early removal have been proposed after pulmonary surgery but not after RAMIE. The study concept is based on our own experience and the promising current results of the RAMIE procedure. Therefore, the presented randomized controlled trial will provide statistical evidence of the effectiveness and feasibility of the "drainless" RAMIE. TRIAL REGISTRATION: ClinicalTrials.gov NCT05553795. Registered on 23 September 2022.


Assuntos
Neoplasias Esofágicas , Robótica , Humanos , Esofagectomia/métodos , Complicações Pós-Operatórias/etiologia , Abdome , Neoplasias Esofágicas/cirurgia , Dor Pós-Operatória/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
2.
J Investig Allergol Clin Immunol ; 33(6): 446-456, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36000830

RESUMO

BACKGROUND AND OBJECTIVE: Positive bronchodilator reversibility (BDR) is a diagnostic criterion for asthma. However, patients with asthma may exhibit a negative BDR response. Aim: To describe the frequency of positive and Negative BDR response in patients with severe asthma and study associations with phenotypic characteristics. METHODS: A positive BDR response was defined as an increase in FEV1 >200 mL and >12% upon testing with a short-acting ß-agonist. RESULTS: BDR data were available for 793 of the 2013 patients included in the German Asthma Net (GAN) severe asthma registry. Of these, 250 (31.5%) had a positive BDR response and 543 (68.5%) a egative BDR response. Comorbidities significantly associated with a negative response were gastroesophageal reflux disease (GERD) (28.0% vs 40.0%, P<.01) and eosinophilic granulomatosis with polyangiitis (0.4% vs 3.0%; P<.05), while smoking history (active: 2.8% vs 2.2%; ex: 40.0% vs 41.7%) and comorbid chronic obstructive pulmonary disease (COPD) (5.2% vs 7.2%) were similar in both groups. Patients with a positive BDR response had worse asthma control (median Asthma Control Questionnaire 5 score, 3.4 vs 3.0, P<.05), more frequently reported dyspnea at rest (26.8% vs 16.4%, P<.001) and chest tightness (36.4% vs 26.2%, P<.001), and had more severe airway obstruction at baseline (FEV1% predicted, 56 vs 64, P<.001) and higher fractional exhaled nitric oxide (FeNO) levels (41 vs 33 ppb, P<0.05). There were no differences in diffusion capacity of the lung for carbon monoxide, single breath (% pred, 70% vs 71%). Multivariate linear regression analysis identified an association between positive BDR response and lower baseline FEV1% (P<.001) and chest tightness (P<.05) and a negative association between BDR and GERD (P<.05). CONCLUSION: In this real-life setting, most patients with severe asthma had a negative BDR response. Interestingly, this was not associated with smoking history or COPD, but with lower FeNO and presence of GERD.


Assuntos
Asma , Síndrome de Churg-Strauss , Refluxo Gastroesofágico , Granulomatose com Poliangiite , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado/fisiologia , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
3.
Eur J Radiol ; 154: 110431, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35803101

RESUMO

PURPOSE: To test the inter-reader agreement of the Prostate Imaging Quality (PI-QUAL) score for multiparametric prostate MRI and its impact on diagnostic performance in an MRI-ultrasound fusion biopsy population. PATIENTS AND METHODS: Pre-biopsy multiparametric (T2-weighted, DWI, and DCE) prostate MRIs (mpMRI) of 50 patients undergoing transrectal ultrasound-guided MRI-fusion (MRI-TRUS) biopsy were included. Two radiologists independently assigned a PI-QUAL score to each patient and assessed the diagnostic quality of individual sequences. PI-RADS categories were assigned to six regions per prostate (left and right: base/mid-glandular/apex). Inter-reader agreement was calculated using Cohen's kappa and diagnostic performance was compared by the area under the receiver operating characteristics curve (AUC). RESULTS: In 274 diagnostic areas, the malignancy rate was 62.7% (22.5% clinically significant prostate cancer, ISUP ≥ 2). Inter-reader agreement for the diagnostic quality was poor for T2w (kappa 0.19), fair for DWI and DCE (kappa 0.23 and 0.29) and moderate for PI-QUAL (kappa 0.51). For PI-RADS category assignments, inter-reader agreement was very good (kappa 0.86). Overall diagnostic performance did not differ between studies with a PI-QUAL score > 3 compared to a score ≤ 3 (p = 0.552; AUC 0.805 and 0.839). However, the prevalence of prostate cancer was significantly lower when the PI-QUAL score was ≤ 3 (16.7% vs. 30.2%, p = 0.008). CONCLUSION: PI-QUAL has only a limited impact on PI-RADS diagnostic performance in patients scheduled for MRI-TRUS fusion biopsy. However, the lower cancer prevalence in the lower PI-QUAL categories points out a risk of false-positive referrals and unnecessary biopsies if prostate imaging quality is low.


Assuntos
Próstata , Neoplasias da Próstata , Biópsia , Humanos , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Ultrassonografia
4.
Sci Rep ; 12(1): 4881, 2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35318350

RESUMO

Historically, thermal radiation is related to 3D cavities. In practice, however, it is known that almost any hot surface radiates according to Planck's law. This approximate universality roots in the smooth electromagnetic mode structure of free space, into which the radiation is emitted. Here, we study the effect for a strongly patterned mode structure and use quasi-transparent point-like thermal light emitters as a probe. As such, we choose current-driven graphene nanojunctions for which the emission into free space obeys Planck's law. Placed in front of a mirror, however, this process is highly sensitive to a node/antinode pattern of light modes. By varying the distance, we can sample the latter with atomic precision, and observe a deep imprint on the observed spectrum. The experiment allows an unprecedented view on thermal radiation in a spatially/spectrally patterned electromagnetic environment.

5.
Pneumologie ; 75(3): 191-200, 2021 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-33728628

RESUMO

The present addendum of the guideline for the diagnosis and treatment of asthma (2017) complements new insights into the diagnosis and management of asthma as well as for the newly approved drugs for the treatment of asthma. Current, evidence-based recommendations on diagnostic and therapeutic approaches are presented for children and adolescents as well as for adults with asthma.


Assuntos
Asma , Pneumologia , Adolescente , Adulto , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Áustria , Criança , Humanos , Sociedades Médicas
6.
Biomol NMR Assign ; 14(2): 339-346, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32803496

RESUMO

The SARS-CoV-2 genome encodes for approximately 30 proteins. Within the international project COVID19-NMR, we distribute the spectroscopic analysis of the viral proteins and RNA. Here, we report NMR chemical shift assignments for the protein Nsp3b, a domain of Nsp3. The 217-kDa large Nsp3 protein contains multiple structurally independent, yet functionally related domains including the viral papain-like protease and Nsp3b, a macrodomain (MD). In general, the MDs of SARS-CoV and MERS-CoV were suggested to play a key role in viral replication by modulating the immune response of the host. The MDs are structurally conserved. They most likely remove ADP-ribose, a common posttranslational modification, from protein side chains. This de-ADP ribosylating function has potentially evolved to protect the virus from the anti-viral ADP-ribosylation catalyzed by poly-ADP-ribose polymerases (PARPs), which in turn are triggered by pathogen-associated sensing of the host immune system. This renders the SARS-CoV-2 Nsp3b a highly relevant drug target in the viral replication process. We here report the near-complete NMR backbone resonance assignment (1H, 13C, 15N) of the putative Nsp3b MD in its apo form and in complex with ADP-ribose. Furthermore, we derive the secondary structure of Nsp3b in solution. In addition, 15N-relaxation data suggest an ordered, rigid core of the MD structure. These data will provide a basis for NMR investigations targeted at obtaining small-molecule inhibitors interfering with the catalytic activity of Nsp3b.


Assuntos
Adenosina Difosfato Ribose/metabolismo , Apoproteínas/química , Betacoronavirus/metabolismo , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Isótopos de Nitrogênio/química , Espectroscopia de Prótons por Ressonância Magnética , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Apoproteínas/metabolismo , Domínios Proteicos , Estrutura Secundária de Proteína , SARS-CoV-2 , Proteínas não Estruturais Virais/metabolismo
7.
Allergy ; 73(4): 862-874, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29318623

RESUMO

BACKGROUND: Allergen-specific immunotherapy can induce long-term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as ß-glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. AIMS: Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)-driven mouse model of allergic asthma. MATERIALS AND METHODS: HDM-sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen-induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue. RESULTS: ESR measurement shows suppression of early allergic response in HDM-SCIT- and DerP1/2-SCIT-treated mice. Both HDM-SCIT and DerP1/2-SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2-SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2-SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL-33, CCL17 and eotaxin levels in lung tissue. DISCUSSION: Taken together, these data show that purified DerP1/2-SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM-induced activation of lung structural cells including airway epithelium. CONCLUSIONS: We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.


Assuntos
Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes/imunologia , Asma/imunologia , Cisteína Endopeptidases/imunologia , Dessensibilização Imunológica/métodos , Animais , Antígenos de Dermatophagoides/administração & dosagem , Proteínas de Artrópodes/administração & dosagem , Cisteína Endopeptidases/administração & dosagem , Dermatophagoides pteronyssinus , Modelos Animais de Doenças , Injeções Subcutâneas , Camundongos
8.
Eur J Nucl Med Mol Imaging ; 45(2): 235-242, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29075832

RESUMO

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.


Assuntos
Tomada de Decisões , Ácido Edético/análogos & derivados , Oligopeptídeos/metabolismo , Tomografia por Emissão de Pósitrons , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Idoso , Ácido Edético/metabolismo , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Ligantes , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Recidiva , Estudos Retrospectivos
9.
Pneumologie ; 71(12): 849-919, 2017 12.
Artigo em Alemão | MEDLINE | ID: mdl-29216678

RESUMO

The present guideline is a new version and an update of the guideline for the diagnosis and treatment of asthma, which replaces the previous version for german speaking countries from the year 2006. The wealth of new data on the pathophysiology and the phenotypes of asthma, and the expanded spectrum of diagnostic and therapeutic options necessitated a new version and an update. This guideline presents the current, evidence-based recommendations for the diagnosis and treatment of asthma, for children and adolescents as well as for adults with asthma.


Assuntos
Asma/diagnóstico , Asma/terapia , Asma/classificação , Asma/etiologia , Áustria , Alemanha , Humanos , Prognóstico , Fatores de Risco , Sociedades Médicas
12.
Allergy ; 71(9): 1274-83, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26990894

RESUMO

BACKGROUND: Regulatory T cells (Treg) represent a promising target for novel treatment strategies in patients with inflammatory/allergic diseases. A soluble derivate of the Treg surface molecule glycoprotein A repetitions predominant (sGARP) has strong anti-inflammatory and regulatory effects on human cells in vitro as well as in vivo through de novo induction of peripheral Treg. The aim of this study was to investigate the immunomodulatory function of sGARP and its possible role as a new therapeutic option in allergic diseases using a humanized mouse model. METHODS: To analyze the therapeutic effects of sGARP, adult NOD/Scidγc(-/-) (NSG) mice received peripheral blood mononuclear cells (PBMC) derived from allergic patients with sensitization against birch allergen. Subsequently, allergic inflammation was induced in the presence of Treg alone or in combination with sGARP. RESULTS: In comparison with mice that received Treg alone, additional treatment with sGARP reduced airway hyperresponsiveness (AHR), influx of neutrophils and macrophages into the bronchoalveolar lavage (BAL), and human CD45(+) cells in the lungs. Furthermore, the numbers of mucus-producing goblet cells and inflammatory cell infiltrates were reduced. To elucidate whether the mechanism of action of sGARP involves the TGF-ß receptor pathway, mice additionally received anti-TGF-ß receptor II (TGF-ßRII) antibodies. Blocking the signaling of TGF-ß through TGF-ßRII abrogated the anti-inflammatory effects of sGARP, confirming its essential role in inhibiting the allergic inflammation. CONCLUSION: Induction of peripheral tolerance via sGARP is a promising potential approach to treat allergic airway diseases.


Assuntos
Inflamação/etiologia , Inflamação/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/metabolismo , Adulto , Alérgenos/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Tolerância Imunológica , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/patologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Hipersensibilidade Respiratória/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
13.
Osteoporos Int ; 27(3): 905-913, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26438309

RESUMO

SUMMARY: Non-hip, non-vertebral fractures (NHNVF) were compared with hip, vertebral and controls. NHNVF were younger and heavier than controls and hip/vertebral fractures in both men and women, respectively. Falls and prior fractures were less common in NHNVF than hip fractures. Glucocorticoid use was lower in NHNVF compared to vertebral fracture (VF) in men. INTRODUCTION: Although hip fracture (HF) and vertebral fractures (VF) receive the most attention in the literature and are the targeted sites for fracture prevention, non-hip, non-vertebral fracture (NHNVF) sites account for a greater proportion of fractures than the hip or vertebrae. This study aimed to assess risk factors for NHNVF and compare them with those for HF, VF and controls. METHODS: Incident fractures during 2005-2007 for men and 1994-1996 for women were identified using computerised keyword searches of radiological reports, and controls were selected at random from electoral rolls for participation in the Geelong Osteoporosis Study. Participants aged 60+ years were included in this study. RESULTS: Compared to controls, men and women with NHNVF were younger (ORs, 0.90, 95% CI 0.86-0.94; and 0.96, 0.93-0.98, respectively) and had a lower femoral neck bone mineral density (BMD) T-score (age-adjusted; difference [men] 0.383, P = 0.002; [women] 0.287, P = 0.001). Compared to HF, men and women with NHNVF were heavier (difference [men] 9.0 kg, P = 0.01; [women] 7.6 kg, P < 0.001). Heavier weight was also a risk factor for women with NHNVF compared to VF (1.03, 1.01-1.06). In men with NHNVF, falls (0.37, 0.14-0.97) and prior fractures (0.38, 0.15-0.98) were less common compared to HF; and glucocorticoid use was less common for NHNVF (0.30, 0.11-0.85) compared to VF. CONCLUSIONS: Given the high numbers of NHNVF sustained by men and women in this study, fracture prevention strategies should focus on individuals with high risk of sustaining these types of fractures, as well as on individuals who are more likely to sustain a HF or VF.


Assuntos
Fraturas por Osteoporose/etiologia , Acidentes por Quedas/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal/fisiologia , Densidade Óssea/fisiologia , Estudos de Casos e Controles , Feminino , Colo do Fêmur/fisiopatologia , Glucocorticoides/efeitos adversos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Fatores de Risco , Fatores Sexuais , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia , Vitória/epidemiologia
14.
N Engl J Med ; 373(3): 232-242, 2015. ilus
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1064859

RESUMO

BACKGROUND:Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina.RESULTS:During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32).


Assuntos
Diabetes Mellitus , Doenças Cardiovasculares , Fosfato de Sitagliptina
15.
Pneumologie ; 68(3): 187-92, 2014 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-24477463

RESUMO

BACKGROUND AND METHODS: Omalizumab is a monoclonal anti-IgE-antibody that is used to treat severe allergic asthma. The aim of this review was to evaluate the available evidence in a panel of experts and to provide recommendations on therapy duration with omalizumab. RESULTS: A direct or indirect interaction between omalizumab and IgE production seems likely. Pharmacokinetic-pharmakodynamic models suggest that omalizumab modulates IgE production. This hypothesis is currently investigated in clinical studies. In addition, available evidence suggests that omalizumab mitigates different factors of airway remodeling. However, based on the currently available data, no recommendations can be given in regard to reduction of dosage or discontinuation of omalizumab in long term treated patients. CONCLUSIONS: Currently, neither dose reductions nor treatment withdrawal can be recommended in patients with severe allergic asthma and long term treatment with omalizumab. Clinical studies addressing these issues are being conducted.


Assuntos
Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Anti-Idiotípicos/imunologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Antialérgicos/administração & dosagem , Antialérgicos/imunologia , Antiasmáticos/administração & dosagem , Antiasmáticos/imunologia , Relação Dose-Resposta a Droga , Humanos , Omalizumab , Resultado do Tratamento
17.
Internist (Berl) ; 53(4): 429-38; quiz 438-9, 2012 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-22349173

RESUMO

Asthma is characterized by variable and reversible airflow limitation and bronchial hyperresponsiveness due to chronic airway inflammation. Asthma treatment is based on the patients' asthma control status. Central to treatment recommendations is anti-inflammatory therapy with inhaled corticosteroids plus a rapid-acting ß(2)-agonist as required. If this is not sufficient to achieve at least partial asthma control, the dose of the inhaled corticosteroid should be increased and a long-acting ß(2)-agonist should be added. Other controllers, such as leukotriene antagonists or slow-release theophylline are alternative or additive options. Systemic treatment with corticosteroids and/or the monoclonal anti-IgE antibody omalizumab are reserved for patients with severe asthma. Strategies aimed at preventing airway irritation, reducing exposure to exogenous allergens and inhaled irritants as well as asthma education are other key elements of asthma management.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Asma/tratamento farmacológico , Asma/prevenção & controle , Antagonistas de Leucotrienos/administração & dosagem , Administração por Inalação , Humanos , Omalizumab
18.
J Clin Pharm Ther ; 37(3): 286-90, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21767284

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Intravenous immunoglobulin (IVIg) is a commonly used therapy for autoimmune disease, but may cause chronic hypertension and thrombosis. We determined whether: (i) IVIg systematically affects blood pressure in the short term; (ii) acute changes in plasma viscosity because of IVIg correlate with blood pressure effects; (iii) effects of IVIg on acute blood pressure are related to baseline blood pressure or hypertension status and (iv) IVIg influences plasma markers of inflammation, anticardiolipin antibodies and homocysteine as additional putative prothrombotic risk factors. METHODS: Twenty adults with autoimmune neurological disease who received a course of IVIg were evaluated immediately before and after each infusion, on every day of the course. Blood pressure, pulse and the following haematological parameters were determined: plasma viscosity, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), haematocrit, fibrinogen, interleukin-6 (IL-6), homocysteine and anticardiolipin positivity. RESULTS: Intravenous immunoglobulin caused both acute and cumulative rises in plasma viscosity across a treatment course, but no concordant changes in blood pressure. There was also no correlation between individual blood pressure changes and viscosity, baseline blood pressure or hypertension status. Levels of IL-6 rose across the course of therapy, but the acute-phase reactants CRP and fibrinogen did not. One patient developed anticardiolipin antibodies during therapy. WHAT IS NEW AND CONCLUSION: Individual courses of IVIg do not systematically raise blood pressure. Where IVIg is found to cause hypertension, this does not appear to be due to a direct effect of IVIg on plasma viscosity.


Assuntos
Doenças Autoimunes do Sistema Nervoso/terapia , Pressão Sanguínea , Viscosidade Sanguínea , Imunoglobulinas Intravenosas/efeitos adversos , Adulto , Idoso , Anticorpos Anticardiolipina/análise , Doenças Autoimunes do Sistema Nervoso/sangue , Doenças Autoimunes do Sistema Nervoso/imunologia , Biomarcadores/sangue , Estudos de Coortes , Feminino , Homocisteína/sangue , Humanos , Hipertensão/etiologia , Imunoglobulinas Intravenosas/uso terapêutico , Interleucina-6/sangue , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Trombose/epidemiologia , Trombose/etiologia , Adulto Jovem
19.
Osteoporos Int ; 22(1): 249-54, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20229198

RESUMO

UNLABELLED: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated even after a subsequent fracture. INTRODUCTION: This study aimed to describe treatment initiation rates for men who had recently sustained a fracture. METHODS: The study was conducted as part of the Geelong Osteoporosis Study in south-eastern Australia. Men in the study area who had sustained an incident fracture in the period July 2006 to December 2007 were identified from hospital radiology reports. A self-report questionnaire was sent to eligible participants approximately 12 months after fracture. Respondents were asked for details of medications prescribed for 'osteoporosis/fracture/low bone mass' before and after fracture, and where applicable, reasons for cessation of treatment. We analysed the results for 109 men aged 50 years and older who had sustained fracture in the study period. RESULTS: Most (75.9%) men potentially eligible for subsidised treatment at the time of fracture remained untreated. Of the 87 men who were untreated, nine had osteoporosis at the hip and/or spine and 29 (26.6%) reported having sustained a low trauma prior fracture. CONCLUSIONS: Our findings are consistent with previously published data showing low rates of treatment initiation in men eligible for osteoporosis treatment. There appear to be barriers involving participants' and medical practitioners' knowledge, beliefs and attitudes regarding osteoporosis and treatment, as well as in the doctor-patient partnership in osteoporosis management. Establishment of clinical pathways for fracture management beyond orthopaedic care may be one of a range of appropriate responses.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/diagnóstico , Padrões de Prática Médica/estatística & dados numéricos , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Uso de Medicamentos/estatística & dados numéricos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Fraturas por Osteoporose/patologia , Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária , Vitória
20.
Osteoporos Int ; 21(6): 909-17, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19707703

RESUMO

SUMMARY: A large population-based random sample of Australian white men was used to provide normative bone mineral density (BMD) data at multiple anatomical sites. The femoral neck BMD data are very similar to those obtained in USA non-Hispanic white males participating in the National Health and Nutrition Examination Survey III (NHANES III). The reference ranges will be suitable for similar populations. INTRODUCTION: To provide normative BMD data for Australian men derived from a large population-based random sample. METHODS: An age-stratified random sample of men was recruited from the Australian electoral rolls (n = 1,467 aged 20-97 years). BMD was quantified at multiple sites using Lunar densitometers. RESULTS: Age-related differences in BMD were best predicted by linear relationships at the spine and hip and by quadratic functions at the whole body and forearm. At the spine, a small age-related increase in mean BMD was observed. Although in the subset with no spinal abnormalities, there was a decrease of 0.003 g/cm(2) per year from age 20. At the hip sites, mean BMD decreased at 0.001-0.006 g/cm(2) per year from age 20. At the forearm and whole body, BMD peaked at 41-47 years. Apart from a small difference in men greater than or equal to 80 years, the Australian femoral neck BMD data are not different to those obtained in USA non-Hispanic white males participating in NHANES III and were generally similar to those of large studies from Canada (CaMos) and Spain. CONCLUSIONS: These data supply BMD reference ranges at multiple anatomical sites that will be applicable to white Australian men and similar populations such as USA non-Hispanic white men.


Assuntos
Densidade Óssea/fisiologia , Absorciometria de Fóton/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Antropometria , Estatura/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Fêmur/fisiologia , Antebraço/fisiologia , Inquéritos Epidemiológicos , Articulação do Quadril/fisiologia , Humanos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
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