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1.
Dig Dis ; 39(5): 496-501, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33588416

RESUMO

BACKGROUND: There is growing evidence about the relationship between sleep quality (SQ) and disease activity in inflammatory bowel disease (IBD). This study aimed to identify the prevalence of sleep disturbance in IBD and its predictive factors and to assess its association with worse outcome. METHODS: IBD patients were prospectively enrolled. Clinical activity, inflammatory activity (high C-reactive protein or fecal calprotectin), and SQ (assessed using the Pittsburgh Sleep Quality Index) were evaluated, and logistic regression was used to identify predictors of poor SQ at baseline. The development of disability or disease progression at 6 months (surgery, hospitalization, development of stenosis, penetrating or perianal disease, steroid dependency, or start/change immunosuppression) was compared between patients with and without poor SQ. RESULTS: Two hundred and five patients were enrolled, with 44.9% (n = 92) reporting poor SQ. On multivariate analysis, current smoking (OR 2.80), extraintestinal manifestations (OR 2.68), clinical activity (OR 3.31), and inflammatory activity (OR 4.62) were predictive factors of poor SQ. Cox proportional hazards model showed that poor SQ was predictive of worse prognosis at 6 months (HR 2.470). CONCLUSION: There is a high prevalence of poor SQ in IBD patients, highlighting the importance of its inclusion in patient-reported outcomes. Sleep disturbance seems to have prognostic value in IBD.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Transtornos do Sono-Vigília , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Complexo Antígeno L1 Leucocitário , Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia
2.
GE Port J Gastroenterol ; 30(Suppl 2): 52-56, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38020819

RESUMO

Introduction: Eosinophilic gastroenteritis (EoG) is a rare condition with a yet poorly understood pathophysiology. Case Presentation: We report on a case of a 36-year-old woman with a history of atopy presenting with nausea, abdominal discomfort, weight loss, and ascites. Laboratorial analysis revealed peripheral eosinophilia and a slight elevation of inflammatory markers. The patient pursued medical assistance several times with a delay in the diagnosis. The pathway to the diagnosis of EoG with serosal infiltration and further management is presented. Discussion: Despite being diagnosed by exclusion, it is important to suspect EoG with subserosa involvement in patients presenting with the uncommon association of peripheral eosinophilia and ascites, particularly if there is a history of atopy.


Introdução: A gastroenterite eosinofílica é uma condição rara, com uma etiologia ainda pouco compreendida. Caso Clínico: Uma mulher de 36 anos, com antecedentes de atopia, que se apresenta com náuseas, desconforto abdominal difuso, perda ponderal e ascite de novo. As análises laboratoriais revelaram eosinofilia periférica e ligeira elevação dos parâmetros inflamatórios. A doente recorreu a cuidados de saúde repetidamente sem um diagnóstico. É apresentado o percurso até ao diagnóstico de gastroenterite eosinofílica com infiltração serosa e tratamento subsequente. Discussão: Apesar de ser um diagnóstico de exclusão, é importante suspeitar de gastroenterite eosinofílica com envolvimento subseroso perante a associação de ascite a sintomas gastrointestinais inespecíficos particularmente em doentes com história de atopia.

3.
GE Port J Gastroenterol ; 29(1): 56-60, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35111965

RESUMO

INTRODUCTION: The first presentation of ulcerative colitis may be an acute flare in about 15% of patients, requiring hospital admission. In acute severe steroid-refractory ulcerative colitis, cytomegalovirus (CMV) should be sought because it is a frequent cause of refractory disease. Herpes simplex colitis constitutes a rarer event in ulcerative colitis patients and it is usually associated with immunosuppression. CASE PRESENTATION: We report a case of a first presentation of ulcerative colitis complicated by CMV and herpes simplex type 2 coinfection. After a long period of systemic corticosteroids, the diagnosis of both CMV and herpes colitis was made. Despite antiviral treatment, colectomy was required due to a contained perforation. DISCUSSION/CONCLUSION: This report highlights the importance of a high degree of suspicion for opportunistic infections in steroid/immunomodulator refractory ulcerative colitis, even in the first flare.


INTRODUÇÃO: A Colite Ulcerosa pode apresentar-se de forma aguda em até 15% dos casos, com necessidade de internamento hospitalar. Na agudização severa de Colite Ulcerosa refractária a corticoterapia deve ser excluída a infeção por Citomegalovirus (CMV), dado tratar-se de uma causa frequente de doença refractária. A colite por Herpes simplex é mais rara nos doentes com Colite Ulcerosa e associa-se frequentemente a imunossupressão. DESCRIÇÃO DO CASO: Relata-se a apresentação inaugural de Colite Ulcerosa complicada por co-infeção por CMV e herpes simplex tipo 2. Após terapêutica prolongada com corticoids sistémicos, foi diagnosticada colite tanto por CMV como Herpes simplex. Apesar de tratamento anti-vírico, foi necessária colectomia por perfuração cólica. DISCUSSÃO/CONCLUSÃO: Este caso sublinha a importância de um alto grau de suspeição para infeções oportunistas em doentes com doença refractária a corticóide/imunomoduladores, mesmo na primeira agudização.

4.
GE Port J Gastroenterol ; 26(6): 404-413, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31832495

RESUMO

Chronic pancreatitis (CP) is a complex disease that should be treated by experienced teams of gastroenterologists, radiologists, surgeons, and nutritionists in a multidisciplinary environment. Medical treatment includes lifestyle modification, nutrition, exocrine and endocrine pancreatic insufficiency correction, and pain management. Up to 60% of patients will ultimately require some type of endoscopic or surgical intervention for treatment. However, regardless of the modality, they are often ineffective unless smoking and alcohol cessation is achieved. Surgery retains a major role in the treatment of CP patients with intractable chronic pain or suspected pancreatic mass. For other complications like biliary or gastroduodenal obstruction, pseudocyst drainage can be performed endoscopically. The recommendations for CP were developed by Clube Português do Pâncreas (CPP), based on literature review to answer predefined topics, subsequently discussed and approved by all members of CPP. Recommendations are separated in two parts: "chronic pancreatitis etiology, natural history, and diagnosis," and "chronic pancreatitis medical, endoscopic, and surgical treatment." This abstract pertains to part II.

5.
GE Port J Gastroenterol ; 26(5): 346-355, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31559325

RESUMO

Chronic pancreatitis (CP) is a heterogeneous disease, with different causes and often a long delay between onset and full classic presentation. Clinical presentation depends on the stage of the disease. In earlier stages, recurrent episodes of acute pancreatitis are the major signs dominating clinical presentation. As the inflammatory process goes on, less acute episodes occur, and pain adopts different aspects or may even disappear. After 10-15 years from onset, functional insufficiency occurs. Then, a classic presentation with pain and pancreatic exocrine and endocrine insufficiency appears. Diagnosis remains challenging in the early stages of the disease, as its initial presentation is usually ill-defined and overlaps with other digestive disorders. Computed tomography and magnetic resonance cholangiopancreatography should be the first choice in patients with suspected CP. If the results are normal or equivocal but still there is a high suspicion of CP, the next option should be endoscopic ultrasound. Endoscopic retrograde cholangiopancreatography is mainly a therapeutic technique, and for the diagnostic purpose should only be used when all other imaging modalities and pancreatic function tests have been exhausted. Indirect tests are used to quantify the degree of insufficiency in already-established late CP. Recommendations on CP were developed by Clube Português do Pâncreas (CPP), based on literature review to answer predefined topics, subsequently discussed and approved by all members of CPP. Recommendations are separated in two parts: "chronic pancreatitis etiology, natural history, and diagnosis," and "chronic pancreatitis medical, endoscopic, and surgical treatment." This abstract pertains to part I.


A pancreatite crónica (PC) é uma doença heterogénea, com diferentes etiologias, muitas vezes, com um longo período entre o início de sintomatologia e a apresentação clínica clássica. A clínica depende do estadio da doença, sendo que nos estadios iniciais, predominam episódios recorrentes de pancreatite aguda; com a progressão da doença, os episódios agudos tornam-se menos frequentes, e a dor adota padrões diferentes, podendo inclusive desaparecer; a insuficiência funcional desenvolve-se 10 a 15 anos após o início, assumindo-se então, a apresentação clássica com dor, insuficiência pancreática exócrina e endócrina. O diagnóstico pode ser desafiador nos estadios iniciais da doença, já que a apresentação inicial é geralmente mal definida e se sobrepõe a outros patologias gastrointestinais. A TAC e CPRM devem ser os primeiros métodos de imagem em doentes com suspeita de PC. Se os resultados forem normais ou ambíguos, a próxima opção deve ser a ecoendoscopia. A CPRE é uma técnica principalmente terapêutica, sendo que para fins de diagnóstico, deve ser reservada para quando todas os outros exames de imagem/testes de função pancreática forem inconclusivos. Testes indiretos de função pancreática devem ser usados para quantificação do grau de insuficiência pancreática em doentes com PC já estabelecida. As recomendações sobre PC foram desenvolvidas pelo Clube Português do Pâncreas (CPP), com base numa revisão da literatura para responder a questões predefinidas, posteriormente discutidos e aprovados por todos os membros do CPP. As recomendações encontram-se separadas em duas partes: "etiologia da pancreatite crónica, história natural e diagnóstico" e "tratamento médico, endoscópico e cirúrgico da pancreatite crónica." Este resumo corresponde à parte I.

6.
Peptides ; 29(7): 1255-70, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18396350

RESUMO

The major active product of ghrelin gene is a 28-amino acid peptide acylated at the serine 3 position with an octanoyl group, called simply ghrelin. Ghrelin has a multiplicity of physiological functions, affecting GH release, food intake, energy and glucose homeostasis, gastrointestinal, cardiovascular, pulmonary and immune function, cell proliferation and differentiation and bone physiology. Nevertheless, recent developments have shown that ghrelin gene can generate various bioactive molecules besides ghrelin, mainly des-acyl ghrelin and obestatin, obtained from alternative splicing or from extensive post-translational modification. Although their receptors have not yet been identified, they have already proven to be active, having intriguingly subtle but opposite physiological actions to ghrelin. This suggests the existence of a novel endocrine system with multiple effector elements which not only may have opposite actions but may regulate the action of each other. In this review, we summarize the steps which lead to the production of the different ghrelin gene products and examine the most significant differences between them in terms of structure and actions.


Assuntos
Hormônios Peptídicos/genética , Hormônios Peptídicos/fisiologia , Acilação , Processamento Alternativo , Animais , Humanos , Hormônios Peptídicos/metabolismo , Processamento de Proteína Pós-Traducional
7.
Drug Discov Today ; 12(7-8): 276-88, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17395087

RESUMO

Ghrelin, a hormone that is produced mainly by the stomach, was identified originally as the endogenous ligand of the growth hormone secretagogue (GHS) receptor. Ghrelin might also be synthesized in other organs, where it might have autocrine or paracrine effects. GHS receptors are present in tissues other than the hypothalamus and pituitary, which indicates that ghrelin has other effects in addition to stimulating the release of growth hormone. Recently, it has been suggested that ghrelin might be involved in the pathogenesis of many diseases and be a therapeutic target in these diseases. Here, we provide an overview of the physiological effects of ghrelin and of its pathological and potential therapeutic roles.


Assuntos
Obesidade/fisiopatologia , Hormônios Peptídicos/fisiologia , Animais , Grelina , Humanos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Hormônios Peptídicos/antagonistas & inibidores , Hormônios Peptídicos/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Grelina , Transdução de Sinais/efeitos dos fármacos
9.
Eur J Gastroenterol Hepatol ; 29(11): 1258-1263, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28877088

RESUMO

OBJECTIVE: The aim of this study was to evaluate the efficacy/tolerability of a culture-guided approach in the eradication of Helicobacter pylori and identify factors associated with antibiotic resistance/treatment failure. PATIENTS AND METHODS: This retrospective single-center study included patients who underwent culture-guided treatment for H. pylori infection, after two ineffective eradication attempts, between October 2012 and December 2016. We assessed the following demographic and clinical data of the patients: sex, age, BMI, alcohol and tobacco consumption, history of dyspepsia, peptic ulceration and first-degree relatives with gastric cancer, antibiotic susceptibility results, treatment composition, tolerability, and success. The treatment success was confirmed by a monoclonal stool antigen test. RESULTS: Culture-guided treatment was performed in 42 patients (57% women, mean age±SD: 48.9±11.4 years). The rates of antibiotic resistance were as follows: clarithromycin 86%, metronidazole 67%; levofloxacin 52%, tetracycline 2%, and amoxicillin and rifampicin 0%. Double resistance to clarithromycin and metronidazole was found in 59.5% of the patients. Most patients showed resistance to less than three antibiotics, but 31% were resistant to three or more. Intention-to-treat and per-protocol eradication rates were 59.5 and 61.5%. Adverse events occurred in 15 (35.7%) patients, but only two (4.8%) patients did not complete treatment because of adverse events. Only age more than 50 years was associated with resistance to three or more antibiotics. Having a first-degree relative with gastric cancer was associated with treatment failure and having a BMI of at least 25 kg/m protected from failure. CONCLUSION: Third-line culture-guided treatment often fails to eradicate H. pylori infection. We need to find factors other than in-vitro antibiotic resistance to explain these suboptimal results.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Adulto , Fatores Etários , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Índice de Massa Corporal , Claritromicina/uso terapêutico , Feminino , Humanos , Levofloxacino/uso terapêutico , Masculino , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Rifampina/uso terapêutico , Tetraciclina/uso terapêutico
10.
Acta Med Port ; 30(11): 824-826, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29279076

RESUMO

INTRODUCTION: Bowel preparation for colonoscopy and/or colorectal surgery can cause electrolyte imbalances. The risk of electrolyte imbalances seems to be related to the type of bowel cleansing solution, age of patients and comorbidities. CASE REPORT: We report two cases of symptomatic hyponatremia (focal neurological signs and coma) after bowel preparation with sodium picosulfate/magnesium citrate for colonoscopy. In both cases, symptoms related to hyponatremia rapidly disappeared after sodium level correction with intravenous administration of hypertonic saline (3% NaCl). DISCUSSION: Electrolyte imbalances are more common with sodium phosphate-based solutions (NaP) and sodium picosulfate/magnesium citrate, in patients older than 65, in patients treated with thiazide diuretics, angiotensin-converting-enzyme inhibitor, betablockers or antidepressants and in gastrectomized patients. These patients should use macrogol-based solutions (polyethylene glycol). CONCLUSION: In patients at risk (patient > 65 years old, patients taking thiazide diuretics, angiotensin-converting-enzyme inhibitors, beta-blockers and antidepressants and with previous gastrectomy) we recommend macrogol-based solutions.


Introdução: A preparação intestinal para colonoscopia e/ou cirurgia coloretal pode induzir alterações hidro-eletrolíticas. O risco destas alterações parece estar relacionado com o tipo de preparação intestinal, idade e comorbilidades dos doentes. Caso Clínico: Os autores apresentam dois casos de hiponatrémia sintomática (sinais neurológicos focais e coma) após preparação intestinal com picossulfato de sódio/citrato de magnésio para colonoscopia. Em ambos os casos, verificou-se resolução completa e rápida do quadro clínico depois da correção da hiponatrémia com solução intravenosa de NaCl a 3%. Discussão: Os distúrbios eletrolíticos são mais frequentes nas preparações à base de fosfato de sódio e picossulfato de sódio/citrato de magnésio, nos doentes com mais de 65 anos ou medicados com diuréticos tiazídicos, inibidores da enzima de conversão da angiotensina, beta-bloqueantes e antidepressivos e em doentes gastrectomizados. Nestes doentes devemos preferir preparações intestinais à base de macrogol (polyethylene glycol). Conclusão: Em doentes de risco (idade superior a 65 anos, medicados com diuréticos tiazídicos, IECAs, beta-bloqueantes e antidepressivos, e antecedentes de gastrectomia) recomendamos soluções à base de macrogol.


Assuntos
Catárticos/efeitos adversos , Citratos/efeitos adversos , Ácido Cítrico/efeitos adversos , Colonoscopia , Hiponatremia/induzido quimicamente , Compostos Organometálicos/efeitos adversos , Picolinas/efeitos adversos , Cuidados Pré-Operatórios/métodos , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
12.
Therap Adv Gastroenterol ; 10(9): 651-660, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28932267

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. METHODS: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. RESULTS: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. CONCLUSIONS: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.

13.
EBioMedicine ; 21: 123-130, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28629912

RESUMO

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62µg/mL vs. 1.15µg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3µg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250µg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.


Assuntos
Anticorpos/imunologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Fatores Imunológicos/efeitos adversos , Infliximab/efeitos adversos , Complexo Antígeno L1 Leucocitário/metabolismo , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticorpos/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Endoscópios , Feminino , Humanos , Fatores Imunológicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Infliximab/farmacocinética , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Razão de Chances , Modelos de Riscos Proporcionais
14.
Br J Pharmacol ; 147(6): 690-7, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16415904

RESUMO

Acute effects of angiotensin II (AngII) on diastolic properties of the myocardium were investigated. Increasing concentrations of AngII (10(-9) to 10(-5) M) were added to rabbit papillary muscles in the absence (n=11) or presence of: (i) AT1 receptor antagonists, losartan (10(-6) M; n=7) or ZD-7155 (10(-7) M; n=8); (ii) ZD-7155 (10(-7) M) plus AT2 receptor antagonist PD-123,319 (2 x 10(-6) M; n=6); (iii) PKC inhibitor, chelerythrine (10(-5) M; n=8); or (iv) Na(+)/H(+) exchanger (NHE) inhibitor, 5-(N-methyl-N-isobutyl)-amiloride (10(-6) M; n=10). Passive length-tension relations were constructed before and after a single concentration of AngII (10(-5) M, n=6). Effects of AngII infusion (10 microg kg(-1) min(-1)) were evaluated in in situ rabbit hearts. AngII concentration dependently increased inotropy and resting muscle length (RL). At 10(-5) M, active tension increased 43.3+/-6.25% and RL 1.96+/-0.4%. Correcting RL to its initial value resulted in a 46+/-4% decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the right and downward shift of the passive length-tension relation promoted by AngII. In the intact heart, at matched systolic pressures of 112 mmHg, AngII decreased end-diastolic pressures from 10.3+/-0.3 to 5.9+/-0.5 mmHg, and minimal diastolic pressures from 8.4+/-0.5 to 4.6+/-0.6 mmHg. AT1 blockade inhibited AngII effects on myocardial inotropy and stiffness, while PKC or NHE inhibition only significantly attenuated its effects on resting length and tension. In conclusion, AngII decreases myocardial stiffness, an effect that requires AT1 receptor activation and is mediated by PKC and NHE. This represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that AngII is a powerful regulator of cardiac filling.


Assuntos
Angiotensina II/farmacologia , Coração/efeitos dos fármacos , Contração Miocárdica , Miocárdio/enzimologia , Proteína Quinase C/metabolismo , Receptor Tipo 1 de Angiotensina/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Alcaloides , Amilorida/análogos & derivados , Amilorida/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Benzofenantridinas , Diástole , Relação Dose-Resposta a Droga , Elasticidade , Losartan/farmacologia , Masculino , Naftiridinas/farmacologia , Fenantridinas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Coelhos , Receptor Tipo 1 de Angiotensina/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Função Ventricular Esquerda
15.
Peptides ; 27(7): 1616-23, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16417945

RESUMO

Contractile effects of ghrelin (10(-9) to 10(-6) M) were tested in rat papillary muscles of normal (n = 50) and hypertrophic (n = 16) right ventricles (RV). RV hypertrophy was induced by pulmonary hypertension using monocrotaline. In normal muscles, ghrelin was added either alone (n = 9) or after pre-treatment with indomethacin (cycloxygenase inhibitor, 10(-5) M; n = 10), L-nitro-L-arginin (NO synthase inhibitor, 10(-4) M; n = 9), D-Lys(3)-GHRP-6 (GHS-R1a antagonist; 10(-4) M; n = 8) or apamin+charybdotoxin (KCa channels blockers; 10(-6) M, n =7 ), as well as after damaging the endocardial endothelium (n = 7). In hypertrophic muscles, ghrelin was added either alone (n = 9) or after pre-treatment with apamin+charybdotoxin (10(-6 M, n=7). Ghrelin concentration-dependently decreased active tension (AT) and maximal velocity of tension rise (negative inotropic effect), as well as, maximal velocity of tension decay (negative lusitropic effect) and time to AT (onset of relaxation). These effects were maximal at 10(-6) M, similar in normal and hypertrophic muscles and were significantly altered only by apamin+charybdotoxin, indomethacin and L-nitro-L-arginin. Apamin+charybdotoxin attenuated the negative inotropic effect, while indomethacin and L-nitro-L-arginin, respectively, blunted and exacerbated the premature onset of relaxation. In conclusion, ghrelin induces negative inotropic and lusitropic effects and an earlier onset of relaxation in normal and hypertrophic myocardium, which are independent of GHS-R1a, since they were not affected by D-Lys(3)-GHRP-6. The negative inotropic effect is partly mediated by KCa channels, while the earlier onset of relaxation is modulated by prostaglandins and NO.


Assuntos
Endocárdio/metabolismo , Hipertrofia Ventricular Direita/tratamento farmacológico , Hipertrofia Ventricular Direita/patologia , Óxido Nítrico/metabolismo , Hormônios Peptídicos/fisiologia , Canais de Potássio/metabolismo , Prostaglandinas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Apamina/farmacologia , Charibdotoxina/farmacologia , Grelina , Humanos , Indometacina/farmacologia , Monocrotalina/metabolismo , Nitroarginina/farmacologia , Oligopeptídeos/farmacologia , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/farmacologia , Peptídeos/química , Ratos , Receptores de Grelina
16.
Rev Port Cardiol ; 24(10): 1235-42, 2005 Oct.
Artigo em Inglês, Português | MEDLINE | ID: mdl-16398240

RESUMO

INTRODUCTION: Ghrelin, isolated in 1999, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Recent studies suggest that it may influence the function of normal and failing hearts. Nonetheless, it has been difficult to differentiate its effects on the intrinsic properties of the myocardium from the secondary effects resulting from growth hormone release and vasomotor action. This study investigated the contractile effects of ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium. METHODS: Adult Wistar rats randomly received monocrotaline (MCT; n=9; 60 mg/kg, s.c.) or vehicle (n=7; 1 ml/kg). Three weeks later, after right ventricular (RV) hemodynamic evaluation, the effects of 10(-6) M of a pentapeptide active fragment of ghrelin (fG) were tested on contractile parameters of RV papillary muscles (Normal, n=7; MCT, n=9). GHS-R1a mRNA expression was estimated in RV transmural free-wall samples (Normal, n=7; MCT, n=9), using real-time RT-PCR. RESULTS: In the Normal group, fG reduced active tension (AT), maximum velocity of tension rise (dT/dt(max)) and maximum velocity of tension decline (dT/dt(min)), by 27.9 +/- 4.0%, 28.5 +/- 6.7% and 21.4 +/- 4.2% respectively. In the MCT group, fG reduced AT, dT/dt(max) and dT/dt(min) by 24.1 +/- 6.3%, 24.3 +/- 6.5% and 24.5 +/- 6.1% respectively. GHS-R1a mRNA expression was similar in the two groups (Normal: 2.3*10(5) +/- 5.4*10(4); MCT: 3.0*10(5) +/- 1.1*10(5): p > 0.05). CONCLUSION: This study shows that ghrelin has negative inotropic and lusitropic effects. These effects and expression of its receptor are preserved in RV hypertrophy, suggesting that ghrelin may be a new target in progression to heart failure.


Assuntos
Hormônio do Crescimento/fisiologia , Hipertrofia Ventricular Direita/etiologia , Hipertrofia Ventricular Direita/fisiopatologia , Hormônios Peptídicos/fisiologia , Receptores Acoplados a Proteínas G/biossíntese , Animais , Grelina , Masculino , Contração Miocárdica , Ratos , Ratos Wistar , Receptores de Grelina
17.
GE Port J Gastroenterol ; 22(4): 161-171, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-28868399

RESUMO

Pancreatic cancer is one of the digestive cancers with the poorest prognosis, so an early and correct diagnosis is of utmost importance. With the development of new therapeutic options an accurate staging is essential. Endoscopic ultrasonography (EUS) has a major role in all stages of the management of these patients. EUS has a high accuracy in the diagnosis of pancreatic adenocarcinoma and the possibility to perform fine-needle aspiration/biopsy (FNA/FNB) increases the diagnostic yield of EUS. There is still no consensus on the several technical aspects of FNA, namely on the rapid on-site evaluation (ROSE), the diameter and type of needle, the number of passes and the use of stylet and suction. Contrast-enhanced EUS (CE-EUS) and EUS elastography (EUS-E) have been used in recent years as an adjunct to EUS-FNA. Given the higher sensitivity of these techniques a negative cytology by EUS-FNA should not exclude malignancy when CE-EUS and/or EUS-E are suggestive of pancreatic neoplasia. EUS remains one of the main methods in the staging of pancreatic adenocarcinoma, namely to further evaluate patients with non-metastatic disease that appears resectable on initial imaging. EUS is crucial for an accurate preoperative evaluation of pancreatic cancer which is essential to choose the correct management strategy. The possibility to obtain samples from suspicious lesions or lymph nodes, by means of EUS-guided fine-needle aspiration as well as the use of contrast-enhanced and elastography, makes EUS an ideal modality for the diagnosis and staging of pancreatic cancer.


O adenocarcinoma do pâncreas é uma das neoplasias digestivas com pior prognóstico, sendo fundamental um diagnóstico correto e precoce. Com o desenvolvimento de novas opções terapêuticas é essencial um estadiamento preciso. A ecoendoscopia apresenta um papel relevante em todas as fases da abordagem destes doentes.A acuidade da ecoendoscopia no diagnóstico de adenocarcinoma pancreático é elevada. A possibilidade de realização de punção aspirativa aumenta o potencial diagnóstico, não havendo ainda consenso relativamente a vários aspetos da técnica, nomeadamente em relação à presença de citopatologista durante o procedimento, tipo e diâmetro de agulha, número de passagens e utilização estilete e aspiração. Nos anos recentes tem-se assistido à utilização de ecoendoscopia com contraste (CE-EUS) ou elastografia (EUS-E) como adjuvante da ecoendoscopia. Estas técnicas apresentam elevada sensibilidade e uma citologia negativa não exclui malignidade se a CE-EUS e/ou EUS-E apresentarem características sugestivas de malignidade. A ecoendoscopia mantém-se um dos principais métodos no estadiamento do adenocarcinoma pancreático, em especial na presença de doença não metastática que aparenta ser ressecável noutras técnicas imagiológicas.A ecoendoscopia é fundamental na avaliação pré-operatória do adenocarcinoma pancreático e na definição da correta estratégia de tratamento. A possibilidade de obtenção de amostras de lesões ou adenopatias suspeitas, através de punção aspirativa, assim como a utilização de contraste e elastografia, fazem da ecoendoscopia uma técnica ideal no diagnóstico e estadiamento.

18.
Eur J Gastroenterol Hepatol ; 27(12): 1409-17, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26441206

RESUMO

BACKGROUND/AIM: The patient's perspective on the healthcare that they receive has become increasingly important in the assessment of healthcare quality, especially in chronic diseases such as inflammatory bowel disease (IBD). In this context, the questionnaire QUOTE-IBD (Quality of Care Through the Patient's Eyes with Inflammatory Bowel Disease) was created to assess the healthcare quality from the point of view of a patient with IBD. This questionnaire does not yet have a validated Portuguese version (PT-QUOTE-IBD). We aimed to assess the acceptability, validity, and reliability of PT-QUOTE-IBD. PATIENTS AND METHODS: This was an observational longitudinal unicentric study with three sequential phases: (a) translation and cultural adaptation of QUOTE-IBD that explores the Importance, Performance and Quality Impact of several dimensions of healthcare; (b) assessment of validity by correlation of the results of PT-QUOTE-IBD and visual analogue scales (VAS); and (c) assessment of the reliability of PT-QUOTE-IBD through a second administration of the questionnaire, with a minimum interval of 4 weeks. RESULTS: We included 114 patients with IBD (77 Crohn's disease and 37 ulcerative colitis). Fifty-nine percent of the patients completed all the questions of QUOTE-IBD and VAS. We obtained positive and significant Pearson's correlation coefficients between QUOTE-IBD scores and VAS for Performance and Quality Impact of Total Care and dimensions Accessibility and Information. Thirty-four (30%) patients completed the second questionnaire adequately. We obtained positive and significant Pearson's correlation coefficients between the two questionnaires for Performance and Quality Impact of Total Care, Accessibility, Continuity of Care, Courtesy and Information, and for Performance of Cost. CONCLUSION: PT-QUOTE-IBD is acceptable, valid, and reliable in the assessment of Performance and Quality Impact of Total Care, but not of all dimensions of healthcare.


Assuntos
Doenças Inflamatórias Intestinais/terapia , Satisfação do Paciente , Qualidade da Assistência à Saúde , Adulto , Atenção à Saúde/normas , Feminino , Pesquisa sobre Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Relações Profissional-Paciente , Reprodutibilidade dos Testes , Inquéritos e Questionários
19.
Eur J Gastroenterol Hepatol ; 27(8): 941-50, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25966672

RESUMO

BACKGROUND/AIMS: Structural equation modeling (SEM) is a very popular data-analytic technique for the evaluation of customer satisfaction. We aimed to measure the overall satisfaction of inflammatory bowel disease (IBD) patients with healthcare in Portugal and to define its main determinants using SEM. PATIENTS AND METHODS: The study included three steps: (i) specification of a patient satisfaction model that included the following dimensions: Image, Expectations, Facilities, Admission process, Assistant staff, Nursing staff, Medical staff, Treatment, Inpatient care, Outpatient care, Overall quality, Overall satisfaction, and Loyalty; (ii) sample survey from 2000 patients, members of the Portuguese Association of the IBD; and (iii) estimation of the satisfaction model using partial least squares (XLSTAT-PLSPM). RESULTS: We received 498 (25%) valid questionnaires from 324 (66%) patients with Crohn's disease and 162 (33%) patients with ulcerative colitis. Our model provided a substantial explanation for Overall satisfaction (R=0.82). The mean index of overall satisfaction was 74.4 (0-100 scale). The main determinants of Overall satisfaction were the Image (ß=0.26), Outpatient care (ß=0.23), and Overall quality (ß=0.21), whose mean indices were 83, 75, and 81, respectively. Facilities and Inpatient care were the variables with a significant impact on Overall satisfaction and the worst mean indices. CONCLUSION: SEM is useful for the evaluation of IBD patient satisfaction. The Overall satisfaction of IBD patients with healthcare in Portugal is good, but to increase it, IBD services need to focus on the improvement of Outpatient care, Facilities, and Inpatient care. Our model could be a matrix for a global model of IBD patient satisfaction.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Doenças Inflamatórias Intestinais/terapia , Modelos Estatísticos , Satisfação do Paciente/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Atenção à Saúde/normas , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/psicologia , Portugal , Melhoria de Qualidade/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/normas , Inquéritos e Questionários
20.
Endosc Ultrasound ; 4(3): 244-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26374584

RESUMO

BACKGROUND AND OBJECTIVES: Previous reports assessing the reproducibility of endoscopic ultrasound elastography (EUS-E) in evaluation of solid pancreatic lesions (SPL) involved only experienced endosonographers. We aimed to assess the interobserver agreement (IOA) of EUS-E in the evaluation of SPL by endoscopists with different levels of experience in EUS and EUS-E. MATERIALS AND METHODS: A cross-sectional observational multicenter study was designed and included 11 endoscopists who were divided into four groups: Group A (long experience in EUS and EUS-E); Group B (short experience in EUS and EUS-E); Group C (long experience in EUS and no experience in EUS-E); and Group D (no experience in EUS or EUS-E). The observers independently classified the patterns of 60 video sequences of EUS-E, after a 20-min training session. For each group, we calculated IOA (kappa statistic, k) of EUS-E and the diagnostic accuracy of EUS-E for pancreatic malignancy, by comparing the pattern of EUS-E indicative of malignancy (heterogeneous or homogenous blue) with the final diagnosis. RESULTS: The overall IOA was moderate (k = 0.42; 95% confidence interval (CI) 0.33-0.52). The IOA of Group A (k = 0.80; 95% CI 0.65-1.00) was significantly higher than that of Groups B (k = 0.54; 95%CI 0.40-0.71), C (k = 0.54; 95%CI 0.39-0.68), and D (k = 0.28; 95%CI 0.14-0.40). IOA of Groups B and C was not significantly different, but it was significantly higher than that of Group D. The diagnostic accuracy of Group A (area under the curve under summary receiver operating characteristic (AUROC) = 0.83; 95%CI 0.75-0.90) was not significantly different from that of Group B (AUROC = 0.77; 95%CI 0.71-0.83), but it was significantly higher than that of Groups C (AUROC = 0.74; 95%CI 0.67-0.81) and D (AUROC = 0.74; 95%CI 0.67-0.81). No significant difference was seen between Groups B, C, and D for diagnostic accuracy. CONCLUSION: EUS-E is reproducible in the evaluation of SPL, even between endoscopists with no or limited experience in EUS and/or EUS-E. Reproducibility and diagnostic accuracy increase with experience in EUS and EUS-E.

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