Tuberculose pulmonar causada pelo uso de infliximab em paciente com Doença de Crohn / Pulmonary tuberculosis caused by the use of infliximab in a patient with Crohn's Disease

A doença de Crohn é uma patologia caracterizada pela inflamação transmural do trato gastrointestinal, compondo o espectro das doenças inflamatórias intestinais. Nos casos mais graves, dispõe de tratamento com uso de agentes biológicos e imunomoduladores que podem à reativação ou exacerbação de doenças infecciosas preexistentes. Este relato de caso trata de uma paciente do sexo feminino de 24 anos, diagnosticada com Doença de Crohn há 10 anos, evoluindo com necessidade de tratamento com infliximab e, após período de menos de 1 ano, apresentou odinofagia progressiva, dor abdominal e diarreia, além de perda ponderal, sudorese noturna e febre diária. Tomografia computadorizada de tórax evidenciou árvore em brotamento, sendo confirmado diagnóstico de tuberculose pulmonar pelo Teste Rápido Molecular no escarro e provável tuberculose laríngea e intestinal.

Crohn's disease is a pathology characterized by transmural inflammation of the gastrointestinal tract, comprising the spectrum of Inflammatory Bowel Diseases. In the most severe cases, treatment using biological agents and immunomodulators may be available, which can lead to the reactivation or exacerbation of preexisting infectious diseases. This case report is about a 24-year-old female patient, diagnosed with Crohn's disease 10 years ago, evolving in need of treatment with Infliximab and, after a period of less than 1 year, she presented progressive odynophagia, abdominal pain and diarrhea, in addition to weight loss, night sweats and daily fever. Chest computer tomography showed a tree in bud, and the diagnosis of pulmonary tuberculosis was confirmed by the Rapid Molecular Test in the sputum and probable laryngeal and intestinal tuberculosis.

Eficiência e segurança de secretagogos intestinais para constipação crônica: uma revisão sistemática e meta-análise / Efficacy and safety of intestinal secretagogues for chronic constipation: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Intestinal secretagogues have been tested for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The class-effect of these type of drugs has not been studied. OBJECTIVE: To determine the efficacy and safety of intestinal secretagogues for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. METHODS: A computer-based search of papers from 1966 to September 2017 was performed. Search strategy consisted of the following MESH terms: intestinal secretagogues OR linaclotide OR lubiprostone OR plecanatide OR tenapanor OR chloride channel AND chronic constipation OR irritable bowel syndrome. Data were extracted as intention-to-treat analyses. A random-effects model was used to give a more conservative estimate of the effect of individual therapies, allowing for any heterogeneity among studies. Outcome measures were described as Relative Risk of achieving an improvement in the symptom under consideration. RESULTS: Database Search yielded 520 bibliographic citations: 16 trials were included for analysis, which enrolled 7658 patients. Twelve trials assessed the efficacy of intestinal secretagogues for chronic constipation. These were better than placebo at achieving an increase in the number of complete spontaneous bowel movements per week [RR 1.87 (1.24-2.83)], at achieving three or more spontaneous bowel movements per week [RR 1.56 (1.31-1.85)] and at inducing spontaneous bowel movement after medication intake [RR 1.49 (1.07-2.06)]. Similar results were observed when assessing the efficacy of intestinal secretagogues on constipation-predominant irritable bowel syndrome based on the results of six trials. CONCLUSION: Intestinal secretagogues are useful and safe therapeutic alternatives for the treatment of constipation-related syndromes.

RESUMO CONTEXTO: Os secretagogos intestinais têm sido testados para o tratamento da constipação crônica e síndrome do intestino irritável com constipação predominante. O efeito classe desses tipos de drogas ainda não foi estudado. OBJETIVO: Determinar a eficácia e a segurança de secretagogos intestinais para o tratamento da constipação crônica e síndrome do intestino irritável de constipação predominante. MÉTODOS: Realizada pesquisa baseada em banco de dados de trabalhos publicados entre 1966 e setembro de 2017. A estratégia de pesquisa consistia dos seguintes termos MeSH: secretagogos intestinais OU linaclotide OU lubiprostona OU plecanatide OU tenapanor OU canal de cloro E constipação crônica OU síndrome do intestino irritável. Os dados foram extraídos como análises de intenção de tratar. Um modelo de efeitos aleatórios foi usado para dar uma estimativa mais conservadora do efeito das terapias individuais, permitindo a qualquer heterogeneidade entre os estudos. Os desfechos foram descritos como risco relativo de alcançar uma melhoria no sintoma em consideração. RESULTADOS: A busca no banco de dados rendeu 520 citações bibliográficas: 16 ensaios foram incluídos para análise, que incluiu 7658 pacientes. Doze trabalhos avaliaram a eficácia de secretagogos intestinais para constipação crônica. Estes foram melhores do que placebo, alcançando um aumento no número de evacuações completas espontâneas por semana [RR 1,87 (1,24-2,83)], para a aquisição de três ou mais evacuações espontâneas por semana [RR 1,56 (1,31-1,85)] e na indução espontânea do movimento intestinal após a ingestão de medicação [RR 1,49 (1,07-2,06)]. Resultados semelhantes foram observados ao avaliar a eficácia de secretagogos intestinais na síndrome do intestino irritável de constipação predominante com base em resultados de seis ensaios. CONCLUSÃO: Os secretagogos intestinais são alternativas terapêuticas úteis e seguras para o tratamento de síndromes relacionadas à constipação.

Desarrollo de infección tuberculosa latente y efectos adversos de la isoniazida durante tratamiento con biológico por enfermedad de Crohn / Development of latent tuberculosis and adverse effects with isoniazid during biologist therapy´s in Crohn´s disease / Desenvolvimento de tuberculose latente durante e efeitos adversos da isoniazida o tratamento com biológicos para a doença de Crohn

Los fármacos anti factor de necrosis tumoral alfa (TNF-α) bloquean una de las citoquinas implicadas en la patogénesis de la Enfermedad Inflamatoria intestinal (EII). Su uso se relaciona con aumento de tuberculosis (TB), por lo que el despistaje previo es obligatorio. En la infección tuberculosa latente (ITBL) se utiliza isoniazida como quimioprofilaxis, fármaco que no se encuentra libre de reacciones adversas. Se presenta y discute el caso de una paciente con reacción adversa en piel secundaria al uso de isoniazida.

Anti-tumor necrosis factor alfa drugs are responsible for blocking one of the cytoquines implicated on inflammatory bowel disease pathogenesis. Its use has been linked to an increase in tuberculosis cases which is why screening before starting treatment is mandatory. Latent tuberculosis is treated with isoniazid as chemoprophylaxis although its use may provoke adverse effects. A case is presented of a patient with skin adverse reaction due to the use of isoniazid.

Os medicamentos anti factor de necrose tumoral alfa (TNF-α ) bloqueiam uma das citocinas envolvidas na patogénese da doença inflamatória intestinal (DII). A sua utilização está associada com um aumento da tuberculose (TB), de modo que a despistagem anterior dessa doença é necessária. Na TB latente, frequentemente se utiliza a isoniazida é usado como quimioprofilaxia, uma droga que não está livre de reações adversas. Apresentamos e discutimos o caso de uma paciente com reação adversa na pele secundária ao uso da isoniazida.

Perfil de segurança da terapia anti-TNF na doença de Crohn: um estudo observacional brasileiro comparativo entre infliximabe e adalimumabe / Safety profile of anti-tnf therapy in crohn's disease management: a brazilian single-center direct retrospective comparison between infliximab and adalimumab

ABSTRACT BACKGROUND: Infliximab and adalimumab are considered effective drugs in the management of Crohn's disease. However, due to significant immunossupression, they can cause important adverse events, mostly infections. OBJECTIVE: The aim of this study was to quantify and describe adverse events derived from adalimumab and infliximab use in Crohn's disease patients, and to compare the safety profile between these two agents. METHODS: This was an observational, single-center, longitudinal, retrospective study with Crohn's disease patients under infliximab or adalimumab therapy. Variables analyzed: demographic characteristics (including the Montreal classification), type of agent used, concomitant immunomodulators, presence and types of adverse events observed. Patients were allocated in two groups (infliximab and adalimumab) and had their adverse events accessed and subsequently compared. RESULTS: A total of 130 patients were included (68 in infliximab and 62 in adalimumab groups, respectively). The groups were fully homogeneous in all baseline characteristics, with a median follow-up of 47.21±36.52 months in the infliximab group and 47.79±35.09 in the adalimumab group (P=0.512). Adverse events were found in 43/68 (63.2%) and 40/62 (64.5%) in each group, respectively (P=0.879). There were no differences between the groups regarding infections (P=0.094) or treatment interruption (P=0.091). There were higher rates of infusion reactions in the infliximab group (P=0.016). Cephalea and injection site reactions were more prevalent in adalimumab patients. CONCLUSION: Adverse events were found in approximately two thirds of Crohn's disease patients under anti-TNF therapy, and there were no significant differences between infliximab or adalimumab.

RESUMO CONTEXTO: A utilização de inibidores do fator de necrose tumoral (TNF) alfa no manejo da doença de Crohn é cada vez mais frequente. Tanto o infliximabe quanto o adalimumabe são considerados medicamentos efetivos no controle da doença. Entretanto, por serem potentes imunossupressores, podem causar efeitos adversos importantes, principalmente infecções. OBJETIVO: O objetivo primário deste estudo foi analisar a presença de efeitos adversos dos anti-TNFs em portadores de doença de Crohn, comparando-se infliximabe e adalimumabe e individualizando-se o perfil de segurança de cada droga. MÉTODOS: Estudo observacional, longitudinal e retrospectivo, que incluiu portadores de doença de Crohn com uso de infliximabe ou adalimumabe de uma coorte de pacientes tratados em um único centro. Analisou-se características demográficas (incluindo-se a classificação de Montreal), tipo de agente utilizado, presença e tipo dos eventos adversos observados, entre outras variáveis. Os pacientes foram alocados em dois grupos (infliximabe e adalimumabe) e tiveram os efeitos adversos anotados e posteriormente comparados. RESULTADOS: Um total de 130 pacientes foram incluídos (68 com infliximabe e 62 com adalimumabe). Os grupos foram homogêneos em todas as variáveis analisadas, com tempo de seguimento médio de 47,21±36,52 meses no grupo infliximabe e 47,79±35,09 no grupo adalimumabe (P=0,512). Efeitos adversos foram encontrados em 43/68 (63,2%) e 40/62 (64,5%) nos dois grupos, respectivamente (P=0,879). Não houve diferença entre os grupos em relação a infecções (P=0,094) ou interrupção do tratamento (P=0,091). Houve maiores índices de reações infusionais no grupo infliximabe (P=0,016). Cefaleia e reações no local das injeções foram mais frequentes no grupo adalimumabe. CONCLUSÃO: Efeitos adversos foram encontrados em cerca de dois terços dos pacientes com doença de Crohn em uso de anti-TNF, não havendo maiores diferenças em relação ao uso de infliximabe ou adalimumabe.

Linfoma difuso de células grandes B rectal en un paciente con colitis ulcerosa / Rectal diffuse large B cell lymphoma appearing after immunosuppression for ulcerative colitis: report of one case

Primary colorectal lymphoma is a rare form of presentation of gastrointestinal tract lymphomas. Inflammatory bowel disease and its treatment are risk factors for its development. We report a 47-year-old male patient with Ulcerative Colitis of two years of evolution, treated initially with azathioprine and later on with infliximab. Due to a relapse in symptoms after the second dose of infliximab, a new coloncoscopy was performed showing a rectal ulcerative lesion, corresponding to a large cell Non-Hodgkin's Lymphoma. The patient was successfully treated with RCHOP chemotherapy (Rituximab cyclophosphamide doxorubicin vincristine prednisone). He is currently in disease remission.

Neumonía por Pneumocystis jiroveci post inicio de tratamiento con infliximab en paciente con enfermedad de Crohn / Pneumocystis jiroveci pneumonia following infliximab therapy in patient with Crohn's disease

There are no evidence-based guidelines about prophylaxis against Pneumocystis jiroveci pneumonia in inflammatory bowel disease. We report a case of P. jiroveci pneumonia in patient with Crohn's disease receiving infliximab and methotrexate. This case emphasizes the importance of considering the possibility of this infection in inflammatory bowel disease patients treated on biological therapy.

Anti-TNF-α and hydralazine drug-induced lupus

Drug-induced lupus is a rare drug reaction featuring the same symptoms as idiopathic lupus erythematosus. Recently, with the introduction of new medicines in clinical practice, an increase in the number of illness-triggering implicated drugs has been reported, with special emphasis on anti-TNF-α drugs. In the up-to-date list, almost one hundred medications have been associated with the occurrence of drug-induced lupus. The authors present two case reports of the illness induced respectively by hydralazine and infliximab, addressing the clinical and laboratorial characteristics, diagnosis, and treatment.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Clinical Outcome of Treatment with Infliximab in Crohn's Disease: A Single-Center Experience / 대한소화기학회지

BACKGROUND/AIMS: Our aim was to assess the long-term data regarding efficacy and safety of infliximab (IFX) treatment for refractory Crohn's disease (CD) patients in our tertiary teaching hospital. METHODS: We have retrospectively analyzed the medical records of 89 CD patients who underwent IFX treatment between March 2003 and February 2011 at Kyung Hee University Hospital (Seoul, Korea). The primary outcome measurements were the rates of initial clinical response (CR) at 10 weeks after the 1st IFX infusion and sustained CR at the end of the follow-up. Overall adverse events related to IFX treatment were also evaluated. RESULTS: The mean (SD) follow-up period of eligible 80 patients was 33.7 (21.9) months. A total of 77 patients (96%) showed initial clinical response, but 8 patients showed loss of response to IFX during the follow-up. Finally, 59 patients (59/77, 76.6%) showed sustained CR at the end of the study. Logistic regression analyses showed that an initial CR at 10 weeks was the independent predictor associated with sustained CR (OR 22.286, 95% CI 2.742-132.717, p=0.001). Overall adverse events reported in 18 patients (18/80, 23.3%), including 3 serious infection (pulmonary tuberculosis and herpes zoster). CONCLUSIONS: Treatment with IFX was efficacious and relatively safe for refractory CD patients in Korea. An initial CR at 10 weeks was significantly associated with sustained CR.

The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended? / Aparecimento de psoríase durante o tratamento das doenças inflamatórias intestinais com infliximabe: a terapia biológica deve ser suspensa?

CONTEXT: Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. OBJECTIVE: To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS: A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS: Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION: As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

CONTEXTO: Inúmeros casos paradoxais de lesões psoriásicas induzidas ou exacerbadas por infliximabe têm sido descritos nos últimos anos, existindo discordância quanto à necessidade de interromper o infliximabe, para se conseguir a resolução destas reações adversas cutâneas especificamente em pacientes com doença inflamatória intestinal (DII). OBJETIVO: Revisar sistematicamente a literatura para coletar informações sobre pacientes com DII, que apresentaram essa reação adversa cutânea, focando principalmente na abordagem terapêutica. MÉTODOS: Uma revisão sistemática da literatura foi realizada utilizando as bases de dados Medline, Embase, SciELO e Lilacs. Os estudos publicados foram identificados, analisados †e os dados extraídos. RESULTADOS: Trinta e quatro estudos (69 pacientes com DII) preencheram os critérios de inclusão para a revisão, existindo inconsistência no relato de alguns aspectos clínicos e terapêuticos. A maioria dos pacientes incluídos tinha doença de Crohn (89,86%), era do sexo feminino (47,83%), tinha idade média de 27,11 anos, e sem antecedentes de psoríase (84,05%). Os pacientes desenvolveram principalmente a psoríase tipo placa (40,58%). Houve remissão completa das lesões psoriásicas em 86,96% dos pacientes com DII, existindo diferenças nas abordagens terapêuticas; interrupção do infliximabe determinou a resolução em 47,83% dos casos e 43,48% dos pacientes continuaram recebendo o tratamento com infliximabe. CONCLUSÃO: Uma vez que cresce o número de pacientes com DII com psoríase induzida ou agravada por infliximabe, os médicos devem estar cientes de suas manifestações clínicas, para que o diagnóstico e tratamento adequados sejam devidamente estabelecidos. A decisão sobre continuar ou interromper o infliximabe deve ser individualizada.

Parâmetros digestivos e produção de proteína microbiana em novilhas em crescimento compensatório / Digestive parameters and protein microbial production in heifers under compensatory growth

Avaliaram-se o manejo para crescimento compensatório e o efeito da suplementação com ionóforo na dieta sobre os parâmetros digestivos e sobre a produção de proteína microbiana de novilhas leiteiras. Foram utilizadas 20 animais puros da raça Pardo-Suíça, com média de peso inicial de 200kg aos cinco meses de idade. Os tratamentos foram arranjados em um esquema fatorial 2x2x2, e os animais foram alocados, aleatoriamente, em cada uma das combinações. O fator 1 consistiu dos sistemas de alimentação (convencional e crescimento compensatório), o fator 2, da utilização (200mg de monensina/animal/dia) ou não de ionóforo e o fator 3, dos períodos de alimentação (P1 e P2). A inclusão de ionóforo na dieta aumentou os coeficientes de digestibilidade total da matéria seca, da matéria orgânica, dos carboidratos totais e da fibra em detergente neutro. Não houve efeito do sistema de alimentação, da adição de ionóforo à dieta e do período sobre a produção microbiana. A eficiência microbiana (g PB microbiana/kg de NDT consumido) no período de restrição foi maior que no período de realimentação.

The effects of compensatory growth and ionophore supplementation of diet of dairy heifer on digestive parameters and protein microbial production were evaluated. Twenty five-month-old Brown-Swiss heifers averaging 200kg b.w. were used. The treatments were arranged in a factorial design (2x2x2) with the animals randomly allocated to each of the combinations. Factor 1 was based on the feeding systems (conventional and compensatory growth), factor 2 on ionophore supplementation option (200mg of monensin/animal/day or not) and factor 3, on the feeding periods (P1 and P2). The diet supplemented with ionophore increased the total digestibility coefficients of dry matter, organic matter, total carbohydrates, and neutral detergent fiber. No effect of feeding systems, ionophore supplementation, or feeding periods based on microbial production was oberved. The microbial efficiency (g of microbial crude protein/kg of NDT intake) during the restriction period was higher than the re-feeding period.

A Case of Occupational Rhinitis Caused by Porcine Pancreatic Extract Developing into Occupational Asthma

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

Efficacy and Safety of Treatment with Infliximab in Crohn's Disease: the Experience of Single Center in Korea / 대한소화기학회지

BACKGROUND/AIMS: Infliximab has been shown to be effective and safe for treating refractory luminal and fistulizing Crohn's disease (CD). The aim of this study was to report the efficacy and adverse effect of infliximab therapy in patients with CD at our center. METHODS: Medical records of thirteen patients who were treated with infliximab for refractory luminal or fistulizing CD were reviewed. Clinical response was classified as complete response, partial response and nonresponse. RESULTS: Seven patients were treated for fistulizing CD, four patients for luminal CD, and two for both. The mean time of follow-up was 13.1 months (3.3-28.1 months). Clinical response was seen in 10/13 (77%); complete response 7/13 (54%), partial response 3/13 (23%), nonresponse 3/13 (23%). Mean time to response was 27.1 days (10-41 days). 4 of 10 responders (40%) maintained remission over 30 weeks. Those who started on immunosuppressive treatment more than 3 months before infliximab infusion achieved lower early recurrence rate (14%) compared with those less than 3 months (67%) (p=0.039). Steroid tapering was successful in 7/12 (58%). Five patients required surgical therapy; three nonresponders, one partial responder and one who recurred after initial complete response. Initial responders required less surgery than nonresponders (p=0.035). Acute infusion reactions were seen in 2/40 infusions (5%). One patient developed herpes zoster 20 weeks after infliximab infusion. During follow-up peried, no patient developed serious infection, tuberculosis or malignancy. CONCLUSIONS: Infliximab is effective and safe in clinical practice. Concurrent immunosuppressive use is associated with lower rate of early recurrence.

Effect of cisapride on corrected QT interval in neonates.

OBJECTIVE: To evaluate the effect of cisapride on corrected QT (QTc) interval in neonates at the Queen Sirikit National Institute of Child Health. METHOD: A prospective study was performed to see the effects of cisapride on QTc interval in 20 neonates between 1st July 2001 and 31st January 2002. QTc interval was determined just before, 48 hours, 7 days and 15 days after the start of treatment with cisapride. QTc interval was calculated by averaging QT/square root(RR) values obtained from 5 consecutive beats in lead II of the EKG. Baseline electrolyte and calcium levels were drawn on all infants before treatment of cisapride. Drug dose ranged from 0.1-0.2 mg/kg every 6 to 8 hours. RESULTS: Twenty infants were enrolled in the survey but complete data was obtained on 18 infants only. QTc interval of > 0.45 seconds was not found in any neonate. There was no significant difference of QTc interval before and 48 hours, 7 days and 15 days after cisapride administration (p = 0.861). There were also no statistically significant effects of age at starting cisapride, weight, gestational age and dose on QTc interval (p = 0.581, 0.65, 0.8, and 0.497). There were no adverse effects such as diarrhea or jaundice during the study. CONCLUSION: Term and preterm infants using cisapride at the doses of 0.4-0.8 mg/kg/day did not develop QTc prolongation, arrhythmias or adverse effects. In the absence of risk factors, cisapride may be safe for use in neonates.

Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis.

BACKGROUND: Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis. Its role as monotherapy in the maintenance of disease remission has not been evaluated. METHODS: In this prospective, randomized, open-label study, 25 patients with severe ulcerative colitis received either azathioprine (2.5 mg/Kg/day; Group A, n = 12) or sulfasalazine (6 g/day; Group B, n = 13). All patients received oral corticosteroids in a tapering dosage schedule initially. Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects. RESULTS: Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months (p = ns). Two patients in Group A had to stop azathioprine because of adverse effects (bone marrow suppression and acute pancreatitis). In Group A, all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves. CONCLUSIONS: The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable; there was a trend towards earlier treatment failure with azathioprine.