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1.
Endosc Int Open ; 11(10): E952-E962, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37828974

RESUMO

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

2.
Digestion ; 83(1-2): 41-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20847562

RESUMO

BACKGROUND: Previous reports correlated microalbuminuria with disease activity in patients with Crohn's disease (CD). The aim of the present study is to determine the value of microalbuminuria as a marker for relapses in quiescent CD. METHODS: In a 1-year prospective maintenance trial with oral budesonide in patients with CD in remission, microalbuminuria was measured at randomization, after 2, 6 and 12 months, plus at the time of a relapse. The association of microalbuminuria with the course of disease was analyzed with logistic regression analysis. Time-dependent Cox regression was undertaken to study the association between microalbuminuria and relapse. RESULTS: We included a total of 139 patients. At randomization, microalbuminuria was present in 8 patients. During a 1-year follow-up, 29 patients relapsed and in 11% (3/29), microalbuminuria was present during the relapse. We found no statistically significant association between microalbuminuria and relapse (odds ratio 0.92, 95% confidence interval (CI) 0.76-1.13). Time-dependent Cox regression analysis also revealed no statistical predictive value for microalbuminuria (hazard ratio 1.29, 95% CI 0.37-4.39, p = 0.68). CONCLUSION: Microalbuminuria was moderately prevalent in quiescent CD patients, but it could not be associated with disease characteristics or the type of medication before randomization, nor as a predictor for relapses.


Assuntos
Albuminúria/etiologia , Doença de Crohn/diagnóstico , Doença de Crohn/urina , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Biomarcadores/urina , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Recidiva , Adulto Jovem
3.
Endoscopy ; 40(10): 799-805, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18828075

RESUMO

BACKGROUND AND STUDY AIMS: We have recently proposed a classification of mucosal morphology in Barrett's esophagus based on three criteria: regularity of mucosal pattern, regularity of vascular pattern, and presence of abnormal blood vessels. We aimed to evaluate the interobserver agreement with the proposed mucosal morphology classification and to assess the additional value of narrow band imaging (NBI) over high resolution white light endoscopy (HR-WLE). PATIENTS AND METHODS: Five international experts in the field of Barrett's imaging and seven community endoscopists with no expertise in this field independently evaluated magnified still images from 50 areas, obtained with HR-WLE and NBI, in Barrett's esophagus patients. Visual analogue scales (VAS) were used for scoring imaging quality. Interobserver agreement for mucosal morphology and yield for identifying early neoplasia were assessed. RESULTS: Imaging qualities of NBI were rated more highly than HR-WLE, when evaluated separately as well as in a side-by-side comparison. The interobserver agreement ranged from 0.40 to 0.56 and did not significantly differ between expert and non-expert endoscopists. The overall yield for correctly identifying images of early neoplasia was 81 % for HR-WLE, 72 % for NBI and 83 % for HR-WLE + NBI, with no significant difference between experts and non-experts. CONCLUSION: Interobserver agreement for the classification of mucosal morphology was moderate. Although NBI was rated more highly than HR-WLE for imaging quality, this did not result in improved interobserver agreement or increased yield for identifying early neoplasia in Barrett's esophagus. This applied to non-expert as well as expert endoscopists.


Assuntos
Esôfago de Barrett/patologia , Carcinoma/patologia , Endoscopia , Neoplasias Esofágicas/patologia , Mucosa/patologia , Lesões Pré-Cancerosas/patologia , Esôfago de Barrett/classificação , Competência Clínica , Humanos , Aumento da Imagem , Luz , Microscopia , Mucosa/irrigação sanguínea , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Ned Tijdschr Geneeskd ; 152(31): 1737-42, 2008 Aug 02.
Artigo em Holandês | MEDLINE | ID: mdl-18727606

RESUMO

A 79-year-old woman presented with complaints of upper abdominal pain, nausea and vomiting since a few days. Laboratory tests showed no abnormalities except for some indications of an inflammation. Based on the medical history, physical examination and findings from radiological examination, initially the diagnosis was 'chronic pancreatitis with formation ofa pseudocyst caused by alcohol abuse'. After one week the patient developed cholestatic liver function disorders with elevated serum pancreatic enzymes. A CT scan of the abdomen showed a dilated gallbladder and progression of the cystic lesion in the pancreatic head with compression of the distal common bile duct. An endoscopic retrograde cholangiopancreatography was performed and the findings fitted a diagnosis of an intraductal papillary mucinous neoplasm. Differentiation between an inflammatory or neoplastic origin of cystic lesions in the pancreas can be difficult. There is a risk ofmisdiagnosing a cystic neoplasm for a pseudocyst. This may lead to delays in making the correct diagnosis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/métodos , Cistadenoma Mucinoso/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pseudocisto Pancreático/diagnóstico , Doença Aguda , Idoso , Cistadenoma Mucinoso/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pancreáticas/cirurgia , Pseudocisto Pancreático/cirurgia , Fatores de Tempo , Resultado do Tratamento
5.
Clin Nutr ; 25(5): 765-72, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16698130

RESUMO

BACKGROUND & AIMS: Patients with head and neck carcinomas often loose a significant percentage of weight, which correlates with the complication rate. Only limited information is available on the moment and extent of weight loss and energy intake in time and the relation with type of treatment. The aim of this study was to describe the moment and extent of weight loss and nutritional energy intake in patients with tumors in oral cavity, oropharynx and hypopharynx during diagnosis, treatment and revalidation. METHODS: An observational, prospective study on weight changes and nutritional intake in these patients was carried out during diagnosis, treatment and revalidation in relation to the type of treatment. RESULTS: Forty-seven patients successfully completed the study. A significant difference in mean bodyweight was found for patients treated by radiotherapy during treatment (-3.3 kg, P=0.01) and the early revalidation period (-3.4 kg, P=0.01) and for patients treated with surgery during diagnoses (-1.5 kg, P=0.001) and early revalidation period (1.6 kg, P=0.02). Overall patients lowered their energy intake by 122 kcal/day followed by a significant increase in energy intake during revalidation 326 kcal/day (P=0.04). CONCLUSIONS: The radiotherapy and the concomitant radio-chemotherapy group lost most body weight during treatment and early revalidation. All treatment groups experienced a decrease in energy intake during treatment followed by a significant increase during revalidation.


Assuntos
Caquexia/etiologia , Carcinoma/metabolismo , Terapia Combinada/efeitos adversos , Ingestão de Energia , Neoplasias de Cabeça e Pescoço/metabolismo , Redução de Peso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/terapia , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Prospectivos , Radioterapia/efeitos adversos , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento
6.
Inflamm Bowel Dis ; 11(11): 972-6, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16239842

RESUMO

BACKGROUND: Case reports concerning irreversible renal failure caused by 5-aminosalicylates (5-ASA) have been published. The aim of this study was to investigate the effect of long-term use of 5-ASA on renal function in patients with Crohn's disease (CD). METHODS: This was a retrospective survey in 200 consecutive outpatients with CD. Endogenous creatinine clearance (ECC) was estimated from serum creatinine with the Cockroft and Gault formula. The first ECC was chosen close to the start of 5-ASA and the second was the most recent ECC available. RESULTS: In 153 patients (59 men and 94 women), sufficient data were available for analysis. The interval between ECCs was 11 years, with a mean exposure to 5-ASA of 8.6 years. The cumulative dose of 5-ASA amounted to 9 kg. The ECC declined 0.3 +/- 5 mL/min/yr (from 100 +/- 25 to 92 +/- 28 mL/min; P < 0.01). In a multiple linear regression model, duration of the interval was a significant predictor for change in ECC (P < 0.0001), but cumulative dose of 5-ASA was not predictive (P = 0.30). No interstitial nephritis was reported, and in the 8 patients with the largest decline in ECC, comorbidity causing renal function impairment was present. CONCLUSIONS: The mean decline in ECC of 0.3 mL/min/yr in patients with CD does not exceed the decline expected from physiologic aging. Furthermore, the cumulative dose of 5-ASA was not a predictor for change in renal function. However, as interstitial nephritis caused by 5-ASA may rarely occur, we still advocate measurements of serum creatinine before and during treatment.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/tratamento farmacológico , Mesalamina/efeitos adversos , Mesalamina/uso terapêutico , Insuficiência Renal/induzido quimicamente , Adulto , Envelhecimento , Creatinina/metabolismo , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/induzido quimicamente , Estudos Retrospectivos
7.
Support Care Cancer ; 13(10): 790-6, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16186995

RESUMO

We conducted a prospective, randomised, double-blinded, placebo-controlled pilot study of parenteral nutrition (PN) supplemented with 0.57 g/kg glutamine-dipeptide in a homogeneous group of 32 allogeneic stem cell transplant (SCT) recipients to determine its effect on mucosal barrier injury (MBI). All patients had been prepared with idarubicin, cyclophosphamide and total body irradiation. PN (by continuous infusion) started on SCT day -6 for a median of 19 days. MBI measured by sugar permeability tests, daily mucositis score, daily gut score, and citrulline concentrations was not reduced by glutamine-dipeptide. However, the daily gut score was significantly lower for the glutamine group on SCT +7 (p = 0.001) whilst citrulline was lower (p = 0.03) for the placebo group on SCT day +21. Albumin was significantly lower in the placebo group on SCT day +21 (32+/-4 versus 37+/-3, p = 0.001) whilst CRP was higher (74+/-48 versus 34+/-38, p = 0.003). Other transplant-related complications (infections, acute graft-versus-host disease) were less common although this did not reach statistical significance nor translate into a reduced length of hospital stay or lower mortality. These results indicate that it would be worthwhile conducting a larger trial to see whether or not giving glutamine-dipeptide reduces the 100-day allogeneic transplant-related complications.


Assuntos
Glutamina/administração & dosagem , Transplante de Células-Tronco , Transplante Homólogo , Adolescente , Adulto , Método Duplo-Cego , Feminino , Glutamina/uso terapêutico , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Países Baixos , Projetos Piloto , Placebos
8.
Neth J Med ; 63(7): 275-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16093580

RESUMO

We report a female patient who repeatedly developed pancreatitis after trimethoprim-sulfamethoxazole (TMP/SMX) use. During childhood she had undergone an ureterosigmoidostomy after which she had been on TMP/SMX 480 mg daily as prophylaxis for pyelonephritis for many years. The patient presented with abdominal pain caused by acute pancreatitis. No other cause, except for TMP/SMX use, could be identified. A causal relationship was confirmed by relapse of the pancreatitis after rechallenge. Our case is unique in demonstrating that acute pancreatitis related to the use of TMP/SMX may occur even after long-term treatment. We advise that the medication is discontinued immediately if a causal relationship with pancreatitis is suspected.


Assuntos
Anti-Infecciosos Urinários/efeitos adversos , Pancreatite Necrosante Aguda/induzido quimicamente , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Anti-Infecciosos Urinários/uso terapêutico , Endoscopia Gastrointestinal , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Pancreatite Necrosante Aguda/diagnóstico , Pielonefrite/prevenção & controle , Recidiva , Fatores de Tempo , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
9.
Ned Tijdschr Geneeskd ; 149(8): 385-90, 2005 Feb 19.
Artigo em Holandês | MEDLINE | ID: mdl-15751316

RESUMO

Intestinal failure is characterised by inability of the intestine to absorb sufficient nutrients to maintain the integrity and function of the body. This can be caused by malabsorption due to too short an intestine or an abnormality of the mucosa, or by a severe motility disorder. In addition to dietary measures, the prescription of total parental nutrition (TPN) at home is sometimes necessary. This treatment is a burden on the patient and the risk of complications must be reduced to a minimum. The risks of long-term parenteral nutrition can be limited and the quality of the provision of services can be increased if the co-ordination is in the hands of a centre for home parenteral nutrition. In the Netherlands there are two centres for home-TPN: the St Radboud University Medical Centre in Nijmegen and the University Medical Centre (AMC) in Amsterdam. In both children and adults, the most common indications are the short bowel syndrome and motility disorders. However, the syndromes that cause this are clearly different in the different age groups. Parenteral nutrition can be given for long periods of time. A large variety of complications can occur, related especially to the equipment or the nutrients. When the nutrition is given via a central venous catheter, then sepsis is a serious and possibly life-threatening complication. In case of administration via an arteriovenous shunt, thrombosis of the shunt is the most frequent problem. If the treatment by means of home-TPN fails, then transplantation of the small intestine should be considered.


Assuntos
Enteropatias/terapia , Nutrição Parenteral Total no Domicílio/métodos , Adulto , Criança , Transtornos da Motilidade Esofágica/terapia , Humanos , Enteropatias/fisiopatologia , Intestinos/fisiopatologia , Intestinos/transplante , Nutrição Parenteral Total no Domicílio/efeitos adversos , Síndrome do Intestino Curto/terapia , Resultado do Tratamento
10.
Ned Tijdschr Geneeskd ; 149(8): 391-8, 2005 Feb 19.
Artigo em Holandês | MEDLINE | ID: mdl-15751317

RESUMO

Small bowel transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients where total parenteral nutrition (TPN) therapy for intestinal failure is unsuccessful. Early referral for screening for small bowel transplantation should be considered in patients with permanent intestinal failure who have occlusion of more than 2 major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies, the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation and is further improving. Rejection, bacterial, fungal and viral (Cytomegalovirus, Epstein-Barr-virus) infections, post-transplant lymphoproliferative disease and graft versus host disease are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects ofimmunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.


Assuntos
Intestino Delgado/transplante , Síndrome do Intestino Curto/cirurgia , Adulto , Criança , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Fígado/fisiologia , Nutrição Parenteral Total no Domicílio , Complicações Pós-Operatórias , Qualidade de Vida , Síndrome do Intestino Curto/terapia , Resultado do Tratamento
11.
Dig Dis Sci ; 48(7): 1355-9, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12870795

RESUMO

Osteoporosis is frequent in Crohn's disease. The aim of the study was to assess the rate of bone loss over time retrospectively and the influence of disease-related factors on bone loss. Twenty-nine patients (8 male), admitted for repeated bone mineral density assessments (BMD) were enrolled. BMD measured by dual energy x-ray absoptiometry was expressed in grams per square centimeter, and as sex- and age-matched Z score. The mean interval between BMD assessments was 41 months, during which period 27 patients used corticosteroids (mean dose 8.6 g) and 21 patients some form of bone protective medication. Initial Z scores at a mean age of 41 years were significantly below zero (spine -1.6 +/- 1.4; femur -1.4 +/- 1.4). Over time, no change in absolute BMD was observed accompanied by an improvement in Z scores. At the same time, an increase in body weight and a decrease in erythrocyte sedimentation rate (ESR) was observed. Multilinear regression analysis demonstrated change in ESR as independent predictor for change in femoral Z score. In conclusion, low BMD is frequent in Crohn's disease, but decline of BMD over time was not found, despite ongoing use of corticosteroids.


Assuntos
Densidade Óssea/fisiologia , Doença de Crohn/fisiopatologia , Osteoporose/metabolismo , Adulto , Anti-Inflamatórios/farmacologia , Peso Corporal/fisiologia , Densidade Óssea/efeitos dos fármacos , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Estudos Retrospectivos , Esteroides , Fatores de Tempo
12.
Neth J Med ; 61(4): 105-10, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12852718

RESUMO

In patients with inflammatory bowel disease, assessment of disease activity is important in order to monitor and adjust therapy. In individual patients, disease evaluation is largely based on subjective symptoms. However, for disease evaluation in clinical trials, an objective and reproducible disease activity index is needed. At present, a number of activity indices are available for Crohn's disease and for ulcerative colitis. These indices may be distinguished in more subjective clinical indices, more objective endoscopic and histological indices, and in indices with combinations of both subjective and objective parameters. In the design of a new clinical trial, an appropriate disease activity index should be selected which is based on the patient selection criteria and the aims of the study.


Assuntos
Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Índice de Gravidade de Doença , Ensaios Clínicos como Assunto , Humanos , Seleção de Pacientes
13.
Scand J Gastroenterol ; 38(5): 522-5, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12795463

RESUMO

BACKGROUND: Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-alpha) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-alpha. METHODS: Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-alpha, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab.


Assuntos
Anticorpos Monoclonais/farmacologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Células Secretoras de Gastrina/efeitos dos fármacos , Gastrinas/biossíntese , Fármacos Gastrointestinais/farmacologia , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Bombesina/metabolismo , Feminino , Células Secretoras de Gastrina/metabolismo , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia
14.
Scand J Gastroenterol ; 38(5): 522-525, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-28443771

RESUMO

BACKGROUND: Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-α) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-α. METHODS: Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-α, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab.

15.
Scand J Gastroenterol Suppl ; (239): 11-4, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14743877

RESUMO

Lipids are a component of artificial nutrition. For 20 years lipids covered only a limited percentage of the energy requirement of the patient, depending on parenteral nutrition. Ideas about dose, type and aims of lipids administration in artificial nutrition have changed during this period. The study is based on the discussion around lipids in artificial nutrition.


Assuntos
Emulsões Gordurosas Intravenosas/administração & dosagem , Lipídeos/administração & dosagem , Nutrição Parenteral/métodos , Humanos , Inflamação/dietoterapia , Infusões Intravenosas , Desnutrição/prevenção & controle , Desnutrição/terapia
16.
Scand J Gastroenterol Suppl ; (239): 69-72, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14743886

RESUMO

BACKGROUND: Thiopurines have proven efficacy in inflammatory bowel disease. However, concerns regarding toxicity have limited the use of these agents as first line of medical therapy. METHODS: Review of the literature regarding metabolism, efficacy and side effects. RESULTS: In clinical trials, up to 15% of patients discontinued 6-mercaptopurine or its pro-drug azathioprine prematurely due to adverse events. These events may be divided into dose-independent idiosyncratic reactions and dose-related, pharmacologically explainable toxicity. Dose-independent reactions include skin rash, fever, diarrhoea and pancreatitis. Most frequently observed dose-dependent adverse events are nausea, malaise and myelotoxicity. Furthermore, dose-dependent and dose-independent hepatotoxicity may occur. Recent insights obtained by therapeutic drug monitoring in patients on azathioprine or 6-mercaptopurine have led to strategies to reduce toxicity. One strategy is to detect poor metabolisers of thiopurines by establishing the activity of the key enzyme thiopurine methyltransferase. However, the clinical relevance of this strategy is still a point of debate. Another strategy is to administer 6-thioguanine, which is an agent close to the effective 6-thioguanine nucleotides. CONCLUSION: Therapeutic drug monitoring of thiopurines resulted in strategies to reduce toxicity. The value of these strategies has yet to be proven in prospective randomized trials.


Assuntos
Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina/efeitos adversos , Azatioprina/efeitos adversos , Monitoramento de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Humanos , Resultado do Tratamento
17.
Am J Gastroenterol ; 97(8): 2011-5, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12190169

RESUMO

OBJECTIVE: In Crohn's disease, osteoporosis is frequently found. However, the etiology of osteoporosis remains unclear. The aim of this study was to determine disease-related variables predictive for impaired bone mineral density (BMD). METHODS: A total of 91 patients with Crohn's disease who were admitted for BMD assessment were enrolled in the study. BMD was measured at the femoral neck and lumbar spine by dual energy x-ray absorptiometry (DXA). Results were expressed as T-score and as age- and sex-matched Z-score. Data were obtained by a questionnaire and from patients' medical records. Stepwise linear regression analysis was used to determine independent variables predictive for BMD. RESULTS: Mean age at BMD assessment was 41 +/- 12 yr, duration of disease 11.6 +/- 8.5 yr, and body mass index (BMI) 23.0 +/- 4.1 kg/m2. The cumulative dose of steroids used was 18.7 +/- 19.2 g. Mean Z-scores were less than zero (spine, -1.1 +/- 1.3 SD; femur, -1.1 +/- 1.2 SD; p < 0.0001). A total of 27 patients (30%) fulfilled the World Health Organization criteria for osteoporosis and 46 patients (50%) for osteopenia. Osteoporotic patients used more corticosteroids and had longer duration of disease, lower BMI, and more bowel resections than patients with normal BMD. However, in the linear regression analysis, the only significant independent predictors for BMD of the lumbar spine and femoral neck were BMI and history of bowel resections. BMI and history of resections together accounted for 28% of BMD Z-scores. CONCLUSIONS: BMI and a history of bowel resections were significant predictive variables for BMD. Despite the high dose of steroids used in this study, no detrimental effect could be demonstrated as independent predictor for osteoporosis.


Assuntos
Doença de Crohn/complicações , Glucocorticoides/efeitos adversos , Osteoporose/induzido quimicamente , Prednisolona/efeitos adversos , Absorciometria de Fóton , Adulto , Idoso , Índice de Massa Corporal , Densidade Óssea , Feminino , Fêmur , Glucocorticoides/administração & dosagem , Humanos , Modelos Lineares , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Inquéritos e Questionários
18.
Eur J Clin Invest ; 32(4): 285-9, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11952815

RESUMO

BACKGROUND: Unsaturated fatty acids are known as neutrophil activators. In the present study we investigated whether saturated triglycerides and fatty acids may also contribute to the previously observed activation of neutrophils by nutritional lipid emulsions. Furthermore we tested the hypothesis that carbon-chain length is of importance in this respect. MATERIALS AND METHODS: Neutrophils (1 x 10(6) mL(-1)) were isolated from the blood of nine volunteers. Chemiluminescence was used to evaluate neutrophil activation, characterized by the production of oxygen radicals by neutrophils during incubation with 1 mmol L(-1) saturated fatty acid (6-20 carbon) or triglycerides (6-12 carbon fatty acid), dissolved in aqueous medium by preparing micelles with dipalmitoyl phosphatidylcholine (DPPC). Results were expressed as means +/- SEMs of the overall luminescence signal relative to the signal of cells incubated in medium. RESULTS: Similar to a positive control, the polyunsaturated fatty acid arachidonic acid (C20 : 4), the triglycerides tricaproin (TC6 : 0), tricaprylin (TC8 : 0) and trilaurin (TC12 : 0) as well as the fatty acids lauric acid (C12 : 0), palmitic acid (C16 : 0), stearic acid (C18 : 0) and arachidic acid (C20 : 0) all induced oxygen radical production in neutrophils, while the medium-chain triglyceride tricaprin (TC10 : 0) and fatty acids caproic acid (C6 : 0), caprylic acid (C8 : 0) and capric acid (C10 : 0) exerted no clear effects, similar to negative controls (DPPC and glycerol). CONCLUSIONS: Besides their (poly)-unsaturated counterparts, saturated triglycerides and fatty acids also activate neutrophils. Carbon chain-length is pivotal in the interaction of fatty acids and triglycerides and cells of the immune system.


Assuntos
Ácidos Graxos/química , Ácidos Graxos/farmacologia , Ativação de Neutrófilo/efeitos dos fármacos , Triglicerídeos/química , Triglicerídeos/farmacologia , Adulto , Ácido Araquidônico/farmacologia , Caproatos/farmacologia , Caprilatos/farmacologia , Ácidos Eicosanoicos/farmacologia , Humanos , Técnicas In Vitro , Ácidos Láuricos/farmacologia , Medições Luminescentes , Ácido Palmítico/farmacologia , Ácidos Esteáricos/farmacologia
19.
JPEN J Parenter Enteral Nutr ; 25(6): 352-5, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11688941

RESUMO

BACKGROUND: We have previously reported that medium-chain triglyceride (MCT)-containing lipid emulsions, contrary to long-chain triglyceride (LCT) emulsions, activate human neutrophils. This activation might result from functional alterations in cellular membranes induced by MCT. Membrane fluidity is such a feature with known clinical implications and can be assessed by fluorescence polarization measurements. This study was performed to investigate whether exposure to various emulsions distinctively influences neutrophil membrane fluidity. METHODS: Neutrophils from 8 volunteers were incubated in medium or physiologic 2.5 mmol/L emulsions containing LCT, mixed LCT/MCT, or structured lipids (SL). Subsequently, the cells were washed and anisotropy, ie, the reciprocal of fluidity, was measured using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethyl-ammonium (TMA)-DPH. RESULTS: Compared with nonlipid-exposed neutrophils, LCT/MCT and, to a lesser degree, SL decreased fluorescence anisotropy and thus increased membrane fluidity, which was measured by DPH anisotropy, whereas LCT had no effect. Similar results were obtained with the more polar probe TMA-DPH. CONCLUSIONS: These data suggest that the neutrophil-activating effect of MCT-containing emulsions may, at least in part, be mediated by an effect on cellular membrane fluidity.


Assuntos
Emulsões Gordurosas Intravenosas/química , Ácidos Graxos/química , Fluidez de Membrana/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Adulto , Células Cultivadas , Emulsões Gordurosas Intravenosas/farmacologia , Ácidos Graxos/farmacologia , Feminino , Polarização de Fluorescência , Humanos , Masculino , Fluidez de Membrana/fisiologia , Neutrófilos/fisiologia
20.
JPEN J Parenter Enteral Nutr ; 25(1): 9-13, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11190991

RESUMO

BACKGROUND: To test the hypothesis that structurally different lipid emulsions have distinct immune-modulating properties, we analyzed the elimination of Candida albicans by neutrophils after exposure to various emulsions. METHODS: Neutrophils from 8 volunteers were incubated in physiologic 5 mmol/L emulsions containing long-chain- (LCT), medium-chain- (MCT), mixed LCT/MCT-, alpha-tocopherol-enriched LCT/MCT (LCT/MCT-E), or structured lipids (SL). After washing, the neutrophils were incubated with C. albicans. Phagocytosis was measured as the number of yeast-associated neutrophils relative to the total neutrophil count. Killing was expressed as the percentage of Candida survival relative to the initial yeast cell count. RESULTS: No significant differences in yeast-neutrophil association could be demonstrated after neutrophil incubation in various lipid emulsions or medium, after correction for non-specific adhesion. However, although Candida survival after 1 hour incubation with non-lipid-exposed neutrophils amounted to 53% +/- 11% and was not influenced by LCT (60% +/- 11%), LCT/MCT (78% +/- 7%), LCT/MCT-E (72% +/- 12%), and SL (67% +/- 6%), pure MCT (70% +/- 13%) significantly impaired the killing capacity of neutrophils. CONCLUSIONS: The decreased killing capacity of neutrophils after exposure to medium-chain fatty acid-containing emulsions and the absence of this effect with LCT suggest that lipid emulsions influence the elimination of C. albicans depending on the triglyceride chain length.


Assuntos
Candida albicans/imunologia , Emulsões Gordurosas Intravenosas/farmacologia , Neutrófilos/fisiologia , Fagocitose , Adjuvantes Imunológicos/farmacologia , Adulto , Candida albicans/fisiologia , Candidíase/imunologia , Candidíase/microbiologia , Contagem de Colônia Microbiana , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos
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