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2.
Rev Med Interne ; 40(10): 684-692, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31126662

RESUMO

Clonal hematopoiesis of undetermined significance or CHIP describes the identification, in individuals without hematologic disease, of one or more somatic mutations in hematopoietic cells. These mutations, detected by high-throughput genes sequencing (Next-Generation Sequencing or NGS), affect genes first identified in acute myeloid leukemia or myelodysplastic syndrome, such as DNMT3A, TET2 and ASXL1. CHIP is associated with an increased risk of malignant hemopathy, both myeloid and lymphoid, evaluated from 0.5 to 1% per year. CHIP is also associated with an increased risk of overall mortality and cardiovascular diseases. CHIP detection using NGS is currently limited to basic science field, but recent studies suggest that it may be of clinical interest.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Proteínas de Ligação a DNA/genética , Neoplasias Hematológicas/genética , Hematopoese/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , DNA Metiltransferase 3A , Dioxigenases , Predisposição Genética para Doença , Neoplasias Hematológicas/mortalidade , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Síndromes Mielodisplásicas/genética
3.
World J Gastroenterol ; 14(1): 46-52, 2008 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-18176960

RESUMO

AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72 P < 0.001 and 80 vs 70 P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.


Assuntos
Doença Celíaca/fisiopatologia , Doença Celíaca/psicologia , Nível de Saúde , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
4.
Aquat Toxicol ; 198: 118-128, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29529467

RESUMO

This paper deals with species sensitivity distributions (SSDs) for the lipophilic insecticide lufenuron and benthic arthropods based on sediment-spiked laboratory toxicity tests. This compound that inhibits chitin synthesis and moulting of arthropods persists in sediment. Using field-collected sediment, toxicity tests were conducted with three macro-crustaceans and six insects. The Hazardous Concentration to 5% of the tested species, the HC5 (and 95% confidence limit), derived from an SSD constructed with 10d-LC50's was 2.2 (1.2-5.7) µg/g organic carbon (OC) in dry sediment. In addition, HC5 values derived from SSDs constructed with 28d-LC10 and 28-d LC50 values were 0.13 (0.02-1.50) µg/g OC and 2.0 (1.3-5.5) µg/g OC, respectively. In 28d toxicity tests with Chironomus riparius and Hyalella azteca, a higher sensitivity was observed when using lufenuron-spiked field-collected sediment than in lufenuron-spiked artificial sediment. Overall, the non-biting midge C. riparius appeared to be a representative and sensitive standard test species to assess effects of lufenuron exposure in sediment. The Tier-1 (based on standard test species), Tier-2 (based on standard and additional test species) and Tier-3 (model ecosystem approach) regulatory acceptable concentrations (RACs) for sediment-spiked lufenuron did not differ substantially. The Tier-2 RAC was the lowest. Since to our knowledge this study is the first in the open literature that evaluates the tiered approach in the sediment effect assessment procedure for pesticides, we advocate that similar evaluations should be conducted for pesticides that differ in toxic mode-of-action.


Assuntos
Artrópodes/efeitos dos fármacos , Benzamidas/toxicidade , Bioensaio/métodos , Ecossistema , Sedimentos Geológicos/química , Testes de Toxicidade , Anfípodes/efeitos dos fármacos , Animais , Chironomidae/efeitos dos fármacos , Dose Letal Mediana , Especificidade da Espécie , Poluentes Químicos da Água/toxicidade
5.
Inflamm Bowel Dis ; 11(5): 488-96, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15867589

RESUMO

BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.


Assuntos
Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Doença de Crohn/fisiopatologia , Doença de Crohn/psicologia , Nível de Saúde , Qualidade de Vida , Adulto , Emoções , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Autoimagem , Índice de Gravidade de Doença , Espanha
6.
Inflamm Bowel Dis ; 4(1): 1-5, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9552221

RESUMO

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Quimioterapia Combinada/administração & dosagem , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/imunologia , Eicosanoides/metabolismo , Feminino , Humanos , Interleucina-8/metabolismo , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Comprimidos com Revestimento Entérico
7.
J Appl Physiol (1985) ; 84(1): 327-34, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9451653

RESUMO

Partial liquid ventilation using conventional ventilatory schemes improves lung function in animal models of respiratory failure. We examined the feasibility of high-frequency partial liquid ventilation in the preterm lamb with respiratory distress syndrome and evaluated its effect on pulmonary and systemic hemodynamics. Seventeen lambs were studied in three groups: high-frequency gas ventilation (Gas group), high-frequency partial liquid ventilation (Liquid group), and high-frequency partial liquid ventilation with hypoxia-hypercarbia (Liquid-Hypoxia group). High-frequency partial liquid ventilation increased oxygenation compared with high-frequency gas ventilation over 5 h (arterial oxygen tension 253 +/- 21.3 vs. 17 +/- 1.8 Torr; P < 0.001). Pulmonary vascular resistance decreased 78% (P < 0.001), pulmonary blood flow increased fivefold (P < 0.001), and aortic pressure was maintained (P < 0.01) in the Liquid group, in contrast to progressive hypoxemia, hypercarbia, and shock in the Gas group. Central venous pressure did not change. The Liquid-Hypoxia group was similar to the Gas group. We conclude that high-frequency partial liquid ventilation improves gas exchange and stabilizes pulmonary and systemic hemodynamics compared with high-frequency gas ventilation. The stabilization appears to be due in large part to improvement in gas exchange.


Assuntos
Hemodinâmica/fisiologia , Ventilação de Alta Frequência , Troca Gasosa Pulmonar/fisiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Animais , Animais Recém-Nascidos , Idade Gestacional , Ventilação em Jatos de Alta Frequência , Humanos , Recém-Nascido , Pulmão/patologia , Pulmão/fisiopatologia , Oxigênio/sangue , Circulação Pulmonar/fisiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/patologia , Ovinos , Resistência Vascular/fisiologia
8.
Eur J Gastroenterol Hepatol ; 7(3): 221-6, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7743303

RESUMO

OBJECTIVE: To evaluate the effects of a thromboxane inhibitor on the production of eicosanoids by the colonic mucosa of patients with chronic ulcerative colitis. PATIENTS AND METHODS: Fourteen patients with active left-sided ulcerative colitis were divided into in two treatment groups. Seven patients received oral ridogrel (300 mg twice daily) and seven 5-aminosalicylic acid (5-ASA; 1 g twice daily) for 4 weeks. Intracolonic eicosanoid and elastase release were measured using a colonic double-lumen perfusion technique. An isotonic solution was infused 50 cm from the anal verge at the rate of 5 ml/min, and recovered by siphonage 30 cm distally. Effluents were assayed for thromboxane B2 (TXB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) by radioimmunoassay (RIA), and for polymorphonuclear elastase by immunoactivation. Clinical and colonoscopic criteria were used to determine activity before and after treatment. RESULTS: Four of the seven patients in the ridogrel group and five of the seven in the 5-ASA group showed clinical and colonoscopic improvement. Intraluminal elastase release decreased in every responding patient in the 5-ASA group (P < 0.05) and in three out of seven responders in the ridogrel group. Basal eicosanoid release was similar in both groups. In the responders, 5-ASA significantly reduced the release of the three eicosanoids (P < 0.05). Ridogrel reduced the release of TXB2 to 31% of basal levels (P < 0.01) but the release of PGE2 and LTB4 was not affected. CONCLUSIONS: These results suggest that ridogrel is an oral active selective inhibitor of thromboxane synthetase, which modifies the pattern of colonic eicosanoid generation in patients with chronic ulcerative colitis. Oral ridogrel may be a useful treatment for patients with non-severe ulcerative colitis, although specific indications require further studies.


Assuntos
Colite Ulcerativa/metabolismo , Colo/metabolismo , Dinoprostona/biossíntese , Tromboxano B2/biossíntese , Tromboxano-A Sintase/antagonistas & inibidores , Adulto , Idoso , Ácidos Aminossalicílicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Doença Crônica , Feminino , Humanos , Mucosa Intestinal/metabolismo , Leucotrieno B4/biossíntese , Masculino , Mesalamina , Pessoa de Meia-Idade , Elastase Pancreática/metabolismo , Ácidos Pentanoicos/farmacologia , Piridinas/farmacologia
9.
Eur J Gastroenterol Hepatol ; 11(4): 413-20, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10321759

RESUMO

BACKGROUND: Although there is strong evidence implicating genetic predisposition in the pathogenesis of the chronic inflammatory bowel diseases, the number and identity of susceptibility genes remain uncertain. Cytokine genes are tentative candidate loci, but data regarding association studies in different populations are conflicting. AIMS: To determine potential associations of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF alpha), and tumour necrosis factor beta (TNF beta) gene polymorphisms with ulcerative colitis or subsets of ulcerative colitis in a Spanish population. METHODS: Genotyping for IL-1ra, TNF alpha and TNF beta gene polymorphisms was performed by the polymerase chain reaction in 95 patients with ulcerative colitis and 74 healthy controls. A variable number of tandem repeats (VNTR) in the IL-1ra gene, and a single base pair polymorphism in the TNF alpha gene promoter region (-308) and in the first intron of the TNF beta gene were analysed. Anti-neutrophil cytoplasmic antibodies (ANCA) were detected using an indirect immunofluorescence assay. RESULTS: There were no significant differences between ulcerative colitis patients and controls in either polymorphism analysed, nor between ulcerative colitis subgroups as a function of the clinical disease pattern. However, when stratified by their ANCA status, perinuclear ANCA (p-ANCA) ulcerative colitis showed an increased frequency of the genotype 1,2 of the IL-1ra gene compared with ANCA-negative ulcerative colitis (52% versus 28%; P = 0.02, Pcorr = 0.1). Furthermore, p-ANCA ulcerative colitis had a statistically significant increase of this genotype compared with cytoplasmic ANCA (c-ANCA)/ANCA-negative ulcerative colitis (52% versus 26.5%; P = 0.01, Pcorr = 0.05). CONCLUSIONS: In the Spanish population studied, the polymorphisms analysed in the IL-1ra, TNF alpha and TNF beta genes are unlikely to be important in the overall susceptibility to ulcerative colitis. However, the combination of a subclinical (p-ANCA) and a genetic (IL-1ra gene) marker identified a distinct ulcerative colitis subgroup (p-ANCA; IL-1ra genotype 1,2). These findings provide further evidence of genetic heterogeneity within ulcerative colitis, and support the concept that ANCA may represent a subclinical marker of genetic heterogeneity.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/análise , Colite Ulcerativa/genética , Heterogeneidade Genética , Polimorfismo Genético , Receptores de Interleucina-1/antagonistas & inibidores , Receptores de Interleucina-1/genética , Adolescente , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Feminino , Genótipo , Humanos , Linfotoxina-alfa/genética , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites , Espanha , Fator de Necrose Tumoral alfa/genética
10.
J Crit Care ; 14(1): 20-8, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10102720

RESUMO

PURPOSE: Liquid perfluorochemicals reduce the production of reaction oxygen species by alveolar macrophages. We sought to determine whether the use of liquid perfluorochemicals in vivo during liquid ventilation would attenuate oxidative damage to the lung. MATERIALS AND METHODS: Healthy infant piglets (n = 16) were instrumented for mechanical ventilation and received intravenous oleic acid to create an acute lung injury. The animals were assigned to a nontreatment group receiving conventional mechanical ventilation or a treatment group receiving partial liquid ventilation with a liquid perfluorochemical. Following sacrifice, the bronchoalveolar lavage and lung parenchyma were analyzed for evidence of oxidative damage to lipids and proteins by determination of TBARS and carbonylated protein residues, respectively. RESULTS: Mortality in the control group was 50% at the completion of the study compared with no deaths in the partial liquid ventilation group (P = .025). The alveolar-arterial oxygen difference was more favorable following injury in the partial liquid ventilation group. The liquid ventilation group demonstrated a 32% reduction in TBARS (P = .043) and a 14% reduction in carbonylated protein residues (P = .061). CONCLUSION: These data suggest that partial liquid ventilation supports gas exchange and reduces mortality in association with a reduction in the production of reactive oxygen species and the concomitant attenuation of tissue damage during the early phase of acute lung injury.


Assuntos
Emulsões/farmacologia , Fluorocarbonos/farmacologia , Pulmão/patologia , Respiração com Pressão Positiva , Troca Gasosa Pulmonar/efeitos dos fármacos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Animais , Animais Recém-Nascidos , Hemodinâmica , Hidrocarbonetos Bromados , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Respiração com Pressão Positiva/métodos , Análise de Sobrevida , Suínos
11.
J Investig Allergol Clin Immunol ; 14(2): 159-61, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15301307

RESUMO

A case of a child with Crohn's disease who developed an eosinophilic gastroenteritis is reported. Although symptoms of eosinophilic gastroenteritis at age 8 could mimic those of Crohn's disease, laboratory, radiographic and histologically studies are clearly different. Peripheral blood eosinophilia (7,476 cells per mm3), high serum IgE level (1,050 kU/l) and normal C-reactive protein and erythrocyte sedimentation rate are common in eosinophilic gastroenteritis and uncommon in Crohn's disease. Eosinophilic gastroenteritis was due to bovine serum albumin (BSA) hypersensitivity, confirmed with skin tests, serum levels to specific IgE and a SDS-PAGE IgE-immunoblotting. A strict meat-free diet was started, with progressive relief of symptoms and decrease of eosinophil count twelve months later; the patient became fully symptom-free and eosinophil count was normal.


Assuntos
Doença de Crohn/complicações , Hipersensibilidade Alimentar/complicações , Gastroenterite/complicações , Animais , Bovinos , Criança , Doença de Crohn/imunologia , Eosinofilia/complicações , Eosinofilia/imunologia , Hipersensibilidade Alimentar/imunologia , Gastroenterite/imunologia , Humanos , Imunoglobulina E/sangue , Masculino , Carne , Soroalbumina Bovina/imunologia , Testes Cutâneos
12.
Med Clin (Barc) ; 110(1): 11-5, 1998 Jan 17.
Artigo em Espanhol | MEDLINE | ID: mdl-9527980

RESUMO

BACKGROUND: The aim of the present study was to determine the prevalence and diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) in a Spanish population of patients with inflammatory bowel disease from the province of Tarragona. PATIENTS AND METHODS: One hundred and fifty-six sera obtained from 116 patients with inflammatory bowel disease (75 ulcerative colitis and 41 Crohn's disease) and 40 healthy controls were tested using an indirect immunofluorescence assay. RESULTS: ANCA were detected in 65% of patients with ulcerative colitis but in only 12% of patients with Crohn's disease (p < 0.01), and 2.5% of control subjects (p < 0.01). The overall sensitivity of the test for the diagnosis of ulcerative colitis was 65% with a specificity of 88% and a positive predictive value of 91%. Among patients with ulcerative colitis there was no relationship between the presence or titre of ANCA and the duration, the clinical course, the extent, the disease activity or the need for medical treatment. CONCLUSIONS: In the population studied, ANCA occur more commonly in ulcerative colitis than in Crohn's disease, as reported in other populations. Their determination in patients with inflammatory bowel disease may be useful to differentiate ulcerative colitis from Crohn's disease.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Doenças Inflamatórias Intestinais/sangue , Adulto , Colite Ulcerativa/sangue , Doença de Crohn/sangue , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Sensibilidade e Especificidade , Espanha
13.
Rev Esp Enferm Dig ; 87(9): 665-7, 1995 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-7577126

RESUMO

Esophageal intramural pseudodiverticulosis is an uncommon and benign primary disease of the esophagus. Less than 150 cases have been reported. We report a new case diagnosed by endoscopy during the investigation of an upper gastrointestinal bleeding, in a 48-year-old man who was assymptomatic from the esophageal point of view. We discuss the clinical, pathogenic, diagnostic and therapeutic aspects of this disease.


Assuntos
Divertículo Esofágico/diagnóstico , Diagnóstico Diferencial , Divertículo Esofágico/diagnóstico por imagem , Esofagoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia
14.
Rev Esp Enferm Dig ; 89(4): 280-8, 1997 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-9168661

RESUMO

The quantification of the local production of eicosanoids is of interest because it has been implicated in the mucosal damage of ulcerative colitis. In situ production of eicosanoids is not reflected by its urinary or seric levels, requiring invasive examinations. Thus, new non-invasive techniques such as rectal dialysis have been investigated. The purpose of this study was to assess whether the determination of the intrarectal eicosanoid levels measured by rectal dialysis is useful in detecting the presence of rectal inflammation in patients with ulcerative colitis. Thirty one patients with clinically active colitis and 7 controls with irritable bowel syndrome have been studied. A 10 cm long dialysis bag was placed in the rectum for 1 hour. To determine the variability of the technique, the dialysis was repeated the next day in 6 controls. To detect intrarectal eicosanoids release in inactive colitis, rectal dialysis was performed in another group of 15 patients with clinical and endoscopically inactive colitis and compared with 9 patients with active colitis. PGE2, TXB2, and LTB4 were measured in rectal dialysates by immunospecific RIA. Dialysis was well tolerated by all participants. Intrarectal level of every eicosanoid was much higher in active colitis than in controls (p < 0.05) and in inactive colitis (p < 0.001). The mean coefficient of variation of duplicated dialysis ranged from 15 to 28%. In conclusion, rectal dialysis is a non-invasive technique that allows to prove the presence of active inflammation in ulcerative colitis patients.


Assuntos
Colite Ulcerativa/metabolismo , Eicosanoides/metabolismo , Reto/metabolismo , Adolescente , Adulto , Idoso , Colite Ulcerativa/diagnóstico , Diálise , Eicosanoides/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Clin Ter ; 146(8-9): 491-502, 1995.
Artigo em Italiano | MEDLINE | ID: mdl-8536432

RESUMO

Belonging to the vast family of cytokines, interferons (IFN) have recently been widely investigated concerning their possible clinical applications, both in virology and oncology. In this field results have been quite mixed but definitely encouraging. The best achievements have been obtained in hematology, and particularly in the treatment of hairy cell leukemia and chronic myelogenous leukemia, but new perspectives have also opened in the therapy of solid tumors, especially in the local treatment of superficial bladder cancer and ovarian cancer, AIDS-related Kaposi's sarcoma and malignant melanoma. IFN have in certain cases showed an efficacy comparable to that of classic treatments but with lower toxicity, and in some tumors they have even improved the results obtained so far, especially in combined therapy. We have here gathered the most recent results concerning the use of IFN in the therapy of solid tumors in order to highlight the new therapeutic opportunities available to clinical oncology.


Assuntos
Antineoplásicos/uso terapêutico , Citocinas/uso terapêutico , Interferons/uso terapêutico , Leucemia/tratamento farmacológico , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Antineoplásicos/toxicidade , Antivirais/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Infecções por HIV/complicações , Humanos , Interferons/toxicidade , Leucemia/classificação , Linfoma/tratamento farmacológico , Masculino , Melanoma/etiologia , Neoplasias/classificação , Sarcoma de Kaposi/etiologia
16.
Eur J Histochem ; 57(1): e8, 2013 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-23549467

RESUMO

The aim of the present work was to evaluate the expression of 8-OHdG (8-hydroxydeoxyguanosine) in the benthic fish Zosterisessor ophiocephalus collected in two differently polluted sites of the Venetian lagoon (Porto Marghera and Caroman). We compared our data on 8-OHdG with those of CYP1A (Cytochrome P450, family 1, subfamily A, polypeptide 1), which is a well known biomarker for detoxification of contaminants. Immunohistochemistry with an antibody to 8-OHdG showed immunopositivity in nuclei of hepatocytes as well as in melanomacrophage centres of spleen and kidney, whereas an anti-CYP1A antibody exhibited positive immunostaining in the liver, kidney and ovary. The liver of males showed higher expression of both proteins than females. In animals from Porto Marghera site, the enzymatic assay for 8-OHdG exhibited higher levels in liver of males than in females. Western Blot analysis using the antibody anti-CYP1A recognized the presence of a band of about 60 kDa in the liver of males and females. Males exhibited a strong band, whereas in females the band showed a lower intensity. By using Real-Time PCR, the mRNA expression of CYP1A did not show any differences between males and females from each site, but it was at borderline significance level. Comparing the two sites, mRNA expression of CYP1A was significantly higher in the liver of both males and females from Porto Marghera than that of Caroman. The present data suggest that pollutants are bio-available as demonstrated by our biomarker analyses and may have a harmful effect on aquatic organisms such as Z. ophiocephalus. We report that the highest levels of hepatic 8-OHdG and CYP1A expression were detected in males, showing clear gender specificity.


Assuntos
Núcleo Celular/metabolismo , Citocromo P-450 CYP1A1/biossíntese , Desoxiguanosina/análogos & derivados , Proteínas de Peixes/biossíntese , Regulação Enzimológica da Expressão Gênica , Perciformes/metabolismo , Poluentes da Água/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Desoxiguanosina/biossíntese , Feminino , Itália , Masculino , Especificidade de Órgãos , Caracteres Sexuais
18.
Gut ; 36(3): 363-8, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7698693

RESUMO

Achalasia is considered a primary motility disorder confined to the oesophagus. The lower oesophageal sphincter (LOS) in achalasia is frequently hypertonic and manifests absent or incomplete relaxation in response to deglution. On the other hand, the LOS and the proximal stomach act physiologically as a functional unit whereby relaxation of the LOS during deglution is associated with receptive relaxation of the proximal stomach. Thus, this study investigated the hypothesis that impaired LOS relaxation in patients with achalasia might be associated with impaired relaxation of the proximal stomach. The study consisted of 20 patients with achalasia and 10 healthy controls. Gastric tone variations were quantified using an electronic barostat. Firstly, the study established the basal gastric tone (intragastric volume at the minimal distending pressure+1 mm Hg) and gastric compliance (volume/pressure relation) during isobaric distension (increasing stepwise the intragastric pressure from 0 to 20 mm Hg up to 600 ml). Secondly, the gastric tone response to cold stress (hand immersion into ice water for five minutes) or to control stimuli (water at 37 degrees) was determined. Basal gastric tone mean (SEM) was similar in achalasia and in healthy controls (125 (9) ml v 138 (9) ml, respectively). Compliance was linear and similar in both groups, which also showed similar gastric extension ratios (58 (7) ml/mm Hg v 57 (6) ml/mm Hg). Cold stress induced a gastric relaxatory response that, as a group, was significantly lower in achalasia than in healthy controls (volume: 43 (20) ml v 141 (42) ml; p < 0.05). The responses in each group were not uniform, five of the 20 patients with achalasia showed definite (volume > 100 ml) relaxatory responses whereas four of the 10 healthy controls did not. In conclusion, reflex gastric relaxation is impaired in most patients with achalasia showing that the proximal stomach, and not exclusively the oesophagus, may be effected by the disease.


Assuntos
Acalasia Esofágica/fisiopatologia , Estômago/fisiopatologia , Adolescente , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Temperatura Baixa/efeitos adversos , Complacência (Medida de Distensibilidade) , Esôfago/fisiopatologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia
19.
Crit Care Med ; 21(10): 1479-86, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8403956

RESUMO

OBJECTIVES: a) to determine if continuous nebulization of albuterol is more effective than intermittent nebulization in the treatment of children with status asthmaticus and impending respiratory failure; b) to determine the effect of continuous nebulization and intermittent nebulization on duration of hospital stay and bedside respiratory therapy care. DESIGN: Prospective, randomized study. SETTING: A pediatric intensive care unit (ICU) in a university children's hospital. PATIENTS: Seventeen pediatric asthmatic patients with severe status asthmaticus, with impending respiratory failure (Woods asthma score > or = 5), and without evidence of cardiac or other preexisting lung disease were admitted to the pediatric ICU. The patients were randomized to receive continuous nebulization (n = 9) or intermittent nebulization (n = 8) of albuterol. INTERVENTIONS: The asthmatic patients were randomized into two groups. The continuous group received 0.3 mg/kg/hr of albuterol by continuous nebulization; the intermittent group received 0.3 mg/kg of albuterol over 20 mins every hour. All patients received aerosol therapy through the same delivery system. MEASUREMENTS: Responses to therapy were evaluated by following asthma score, arterial blood gas values, hemodynamics, FIO2, and arterial oxygen saturation initially and at 30 mins, 1 hr, 2 hrs, 4 hrs, then every 4 hrs for a 24-hr time period. Patients were determined to no longer be in impending respiratory failure when their asthma score was < 5 for four consecutive hours. Electrocardiograms, serum electrolyte values, and creatine phosphokinase total and MB fraction values were obtained before and after treatment. Hospital stay and respiratory therapy time, in relative value units (one relative value unit = 10 mins) were analyzed from data collected from therapist bedside flow sheets. RESULTS: The patient characteristics (demographics, hemodynamics, arterial blood gas values, asthma severity, corticosteroid use, theophylline, and beta 2-adrenergic receptor agonist administration) before entry into the study did not differ between groups. Patients in the continuous group improved more rapidly and were out of impending respiratory failure sooner than patients in the intermittent group (continuous group = 12 (median) hrs (range 4 to 24) vs. intermittent group = 18 (median) hrs (range 12 to 24; p = .03). Bedside respiratory therapy time evaluated by relative value units was less for patients who received continuous nebulization of albuterol (continuous group = 14 (median) relative value units (range 6 to 26) vs. intermittent group = 33 (median) relative value units (range 25 to 49; p = .001). Hospital stay was shorter for patients who received continuous nebulization of albuterol (continuous group = 80 [median] hrs [range 51 to 173] vs. intermittent group = 147 [median] hrs [range 95 to 256]; p = .043). Hemodynamics, serum potassium, and creatine phosphokinase concentrations did not differ before and after the study in either group. CONCLUSIONS: In children with impending respiratory failure due to status asthmaticus, continuous nebulization of albuterol is safe and results in more rapid clinical improvement than intermittent nebulization. Respiratory therapy required at the bedside and duration of hospital stay were substantially less for patients receiving continuous nebulization of albuterol, which suggests that continuous nebulization of albuterol is more cost effective than intermittent nebulization.


Assuntos
Albuterol/administração & dosagem , Estado Asmático/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Tempo de Internação , Masculino , Nebulizadores e Vaporizadores , Estudos Prospectivos , Insuficiência Respiratória/prevenção & controle , Terapia Respiratória
20.
Crit Care Med ; 26(9): 1593-5, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9751599

RESUMO

OBJECTIVE: To assess the clinical use of the Dynamic Objective Risk Assessment (DORA) severity of illness score in a site remote from its development. DESIGN: Prospective chart review. SETTING: Tertiary referral pediatric intensive care unit (PICU). PATIENTS: One hundred sixty consecutive admissions involving 621 patient days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pediatric Risk of Mortality (PRISM) scores were collected daily for all PICU patient days. Collection of data was performed by a physician not directly involved in the ordering of vital signs or laboratory data. The daily DORA score was calculated from the previous day's PRISM score and the admission PRISM score according to a previously described formula. The DORA score determines the patient's risk of mortality for the next 24 hrs. Also documented were the tests not ordered for each patient day. The sensitivity and specificity of the DORA score in our patient population were very similar to that previously reported using the previously described 1% cutoff for predicted mortality. We also noted that the tests ordered were related to the physician's perception of the patient's degree of sickness, and were themselves predictive of outcome. CONCLUSION: An outcome scoring system created in one group of PICUs can be applied to patients in another PICU remote from where the scoring system was developed with similar ability to predict outcome.


Assuntos
Estado Terminal/classificação , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Adolescente , Criança , Pré-Escolar , Feminino , Previsões , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Masculino , New York , Avaliação de Resultados em Cuidados de Saúde , Probabilidade , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sobrevida
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