¿Es la mitomicina C superior al 5-fluorouracilo como antimetabolito en la trabeculectomía para el glaucoma? / Is mytomicyn better than 5-fluorouracil as antimetabolite in trabeculectomy for glaucoma?

INTRODUCCIÓN: La trabeculectomía es considerada la intervención de elección en pacientes con glaucoma con indicación de manejo quirúrgico. Dentro de los factores asociados al fracaso de este tratamiento se encuentra la cicatrización postoperatoria. Para disminuir este factor se han usado distintos antimetabolitos, en particular el 5-fluorouracilo y la mitomicina C. Si bien ambos se consideran efectivos, no está claro si existen diferencias entre ambos en relación al éxito de la trabeculectomía y los efectos adversos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis, preparamos tablas de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que en conjunto incluyen 17 estudios primarios, de los cuales, 12 corresponden a ensayos aleatorizados. Concluimos que el uso de mitomicina C podría lograr una mayor disminución de la presión intraocular e incrementar la tasa de éxito calificado en comparación con el 5-fluorouracilo. Sin embargo, su uso podría asociarse a una mayor incidencia de complicaciones.

INTRODUCTION: Trabeculectomy is considered the standard for glaucoma surgery. Postoperative scarring is one the factors associated with surgery failure. Different antimetabolites have been used in order to reduce this risk, particularly 5-fluorouracil and mitomycin C. Although both are considered effective, it is not clear if they are different in terms of success of trabeculectomy and adverse effects. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified four systematic reviews including 17 studies overall, of which 12 were randomized trials. We concluded mitomycin C might be more effective in reducing intraocular pressure and increasing qualified success compared to 5-fluorouracil. However, its use might be associated to a higher risk of complications.

Nódulos reumatoides: avaliação comparativa da resposta terapêutica com triancinolona e fluoruracil intralesional / Rheumatoid nodules: evaluation of the therapeutic response to intralesional fluorouracil and triamcinolone

Os nódulos reumatoides correspondem à manifestação extra-articular mais comum da artrite reumatoide, ocorrendo em cerca de 20-25 por cento dos pacientes. A etiologia é desconhecida. Apesar de os nódulos poderem apresentar remissão espontânea durante o tratamento, eles, em geral, representam um desafio terapêutico. Apresenta-se um caso no qual se avaliou a resposta dos nódulos reumatoides por meio de ultrassonografia após infiltração de triancinolona e 5-fluoruracil.

Rheumatoid nodules are the most common extra-articular manifestation of rheumatoid arthritis and are present in around 20-25 percent of patients. Their etiology is unknown and although the nodules may undergo spontaneous remission during the treatment of rheumatoid arthritis, they usually constitute a therapeutic challenge. The present paper describes a case in which the response of rheumatoid nodules was evaluated by ultrasound following infiltration of triamcinolone acetonide and 5-fluorouracil.

Endoscopic study of the intranasal ostium in external dacryocystorhinostomy postoperative. Influence of saline solution and 5-fluorouracil

PURPOSE: To study, through endoscopy, the postoperative structural changes of the intranasal ostium following external dacryocystorhinostomy and to evaluate the influence of saline solution and 5-fluorouracil. METHODS: Fifty patients were distributed into the following groups: Group SS-dacryocystorhinostomy and an injection of saline solution during surgery (13 patients); Group 5-FU1-dacryocystorhinostomy and an injection of 5 fluorouracil during surgery (17 patients); Group C-dacryocystorhinostomy only (11 patients); Group 5-FU3-dacryocystorhinostomy and 3 injections, 1 during surgery and 1 on the third and fifth postsurgical days (9 patients). RESULTS: Pair-wise group comparisons using the nonparametric Mann-Whitney test revealed that there was a significant reduction of the ostium area only in Group 5-FU1 vs. Group SS on the 60th postoperative day (P <.01); however, a comparative study among the 4 groups using the Kruskal-Wallis test showed no significant changes in the ostium area on the 60th postoperative day. The ostium area within groups at the 30th vs 60th postoperative day was significantly reduced for Group C (P < .05; Mann-Whitney test); no significant changes were found for the other groups. DISCUSSION: These results suggest that the use of 5-fluorouracil in external dacryocystorhinostomy does not significantly influence the final size of the surgical fistula as determined 2 months postsurgery.

OBJETIVO: Estudar, através da endoscopia, as alterações estruturais pós-operatórias do óstio intranasal na dacriocistorrinostomia externa, e avaliar a influência da solução salina e do 5 fluorouracil. MÉTODOS: Cinquenta pacientes foram distribuídos nos seguintes grupos: Grupo SS- 13 pacientes submeteram-se à dacriocistorrinostomia com uso de solução salina; Grupo 5-FU1- 17 pacientes submeteram-se à dacriocistorrinostomia e injeção de 5 fluorouracil; Group C-11 pacientes submeteram-se apenas à dacriocistorrinostomia; Grupo 5-FU3- 9 pacientes submeteram-se à dacriocistorrinostomia associada a três injeções de 5 fluorouracil. RESULTADOS: A comparação pareada pelo teste não paramétrico de Mann-Whitney revelou redução significativa da área do óstio apenas na comparação Grupo 5-FU1 vs. Grupo SS, no 60° dia após a cirurgia (P <.01). No entanto, um estudo comparativo entre os 4 grupos usando o teste de Kruskal-Wallis não revelou diferenças significativas na área do óstio no 60° dia após a cirurgia. Na comparação intra-grupos, a área do óstio no 30° vs 60° dia após a cirurgia mostrou redução significativa para o Grupo C (P < .05; teeste de Mann-Whitney); nenhuma outra comparação apresentou diferenças significativas. DISCUSSÃO: O resultado deste estudo sugere que o uso de 5 fluorouracil na dacriocistorrinostomia externa não influencia significantemente no tamanho final da fístula cirúrgica durante os dois meses de avaliação.

Effect of allopurinol in chronic nonbacterial prostatitis: a double blind randomized clinical trial

INTRODUCTION: The exact mechanism of chronic nonbacterial prostatitis has not been yet elucidated and the outcome with the current management is dismal. In this trial, we studied the effect of allopurinol in the treatment of this disease. MATERIALS AND METHODS: In this randomized double blind controlled trial, a calculated sample size of 56 were grouped into "intervention group" who received allopurinol (100 mg tds for 3 months) with ofloxacin (200 mg tds) for 3 weeks (n = 29) and "control group" who received placebo tablets with ofloxacin (n = 27). PatientsÆ scores based on the National Institute of Health Chronic Prostatitis Symptom Score were recorded before therapy and then every month during the study. A four-glass study was performed before intervention and after 3 months. RESULTS: The 2 groups were similar regarding outcome variables. In the first month of study, a significant but similar improvement in symptom scores was observed in both groups. Microscopic examination of prostate massage and post-massage samples were also similar in both groups. No side effects due to allopurinol were observed in patients. CONCLUSION: We did not find any advantage for allopurinol in the management of chronic prostatitis versus placebo in patients receiving routine antibacterial treatment.

Effect of intracerebroventricular methotrexate on brain amines.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy and cognitive dysfunction. To investigate the role of brain amines in cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Our earlier studies in this regard revealed disruption of brain monoamines in hippocampus with severe cytotoxic effect on CA4 hippocampal neurons. Further extending this study, the levels of brain monoamines in frontal cortex, hypothalamus and brainstem were estimated by HPLC method and histopathological study of the frontal cortex. The concentration of all three-brain amine (norepinephrine, dopamine and serotonin) levels was reduced in 2 mg/kg dose of methotrexate in frontal cortex and brain stem. Hypothalamus did not show any significant change in brain monoamine levels. No structural changes in the frontal cortex neurons were observed. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy. The outcome of the study may have therapeutic implications in the management of childhood lymphoblastic leukemia.

Comparison of external dacryocystorhinostomy and 5-fluorouracil augmented endonasal laser dacryocystorhinostomy. A retrospective review.

PURPOSE: To compare the success rates of external dacryocystorhinostomy (EXT-DCR) with 5-fluorouracil (5-FU) augmented endonasal laser dacryocystorhinostomy (ENL-DCR) and to record the complications associated with 5-FU augmented ENL-DCR MATERIALS AND METHODS: This was a retrospective non-randomised study. Forty-one patients with primary acquired nasolacrimal duct obstruction underwent an EXT-DCR (19 patients) or an ENL-DCR (22 patients) over a 3-year period. A Holmium YAG laser (Ho:YAG) was used in the latter group of patients. Silicone tubes intubated in all patients were removed at three months. 5-FU was applied intraoperatively at the site of the ostium in the ENL-DCR patients. The median follow-up was 12 months (range 3-24 months) for the ENL-DCR group and 22 months (range 6-28 months) for the EXT-DCR group. The patency of the lacrimal system and the severity of epiphora were assessed at a final-review. RESULTS: The median age of the EXT-DCR group was 77 years (range 53-87) and that of the ENL-DCR group was 71 years (range 23 to 84). There were 12 female patients in the former group and 19 in the latter. The percentage of success in the EXT-DCR group was 94.7% (95% confidence interval (CI) = 75.4-99.1) = ), and 63.6% in the ENL-DCR group (95% CI= 43.0-80.3). The confidence interval for the difference of 31.1% was 5.6-52.2. There was a statistically significant difference between the two groups, p=0.024 (Fisher exact test). CONCLUSIONS: These data suggest that EXT-DCR provides better results than 5-FU augmented ENL-DCR. However, ENL-DCR is the procedure of choice in certain circumstances such as in elderly, frail or medically unfit patients. Our results of 5-FU augmented ENL-DCR compare favourably with other published series.

Intracellular studies of the nucleoside reverse transcriptase inhibitor active metabolites: a review

Nucleoside reverse transcriptase inhibitors (NRTIs) plasma concentrations do not correlate with clinical efficacy or toxicity. These agents need to be phosphorylated to become active against HIV-infection. Thus, the characterization of the NRTIs intracellular metabolite pharmacological parameters will provide a better understanding that could lead to the development of more rational dose regimens in the HIV-infected population. Furthermore, intracellular measurements of NRTIs may provide a better marker with respect to clinical efficacy and toxicity than plasma concentrations. Thus, in this article we review the latest information regarding the intracellular pharmacological parameters of zidovudine (ZDV) and lamivudine (3TC) active metabolites in HIV infected patients including the results from our recent clinical studies. We will start the discussion with ZDV and 3TC clinical efficacy, followed by systemic pharmacokinetics studies. We will then discuss the in vitro and in vivo intracellular studies with particular emphasis in the method development to measure these metabolites and we will conclude with the most current data from our clinical trials.

Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas.

Thirty-three eyes of 33 patients were prospectively evaluated to study the short term efficacy, safety, and overall surgical outcome of initial trabeculectomy for primary glaucomas with adjunctive intraoperative or postoperative 5-Fluorouracil (5-FU) use. Twelve eyes serving as controls underwent trabeculectomy without adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10 eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP) was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of patients in the intraoperative and postoperative 5-FU groups, respectively, without use of additional antiglaucoma medications, whereas 66.7% of the patients in the control group achieved similar IOP levels. Hypotony (IOP < 6 mmHg) was seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects were seen exclusively in the postoperative 5-FU group (40%). The use of intraoperative 5-FU exclusively as a mode of antimetabolites delivery seems an acceptable alternative to enhance success rates of trabeculectomy for the primary glaucomas.

Short-term results of initial trabeculectomy with intraoperative or postoperative 5-fluorouracil for primary glaucomas.

Thirty three eyes of 33 patients were prospectively evaluated to study the short term efficacy, and overall surgical outcome of initial trabeculectomy for primary glaucomas with adjunctive intraoperative on postoperative 5-Fluorouracil (5-FU) use. Twelve eyes served as control who underwent trabeculectomy without adjunctive antimetabolites. Eleven eyes received intraoperative 5-FU, while 10 eyes received subconjunctival 5-FU postoperatively. Intraocular pressure (IOP) was maintained below 22 mmHg at 3 months of follow up in 90.9% and 80% of patients in the intraoperative and postoperative 5-FU groups respectively, without use of additional antiglaucoma medications, whereas 66.7% of the patients in the control group achieved similar IOP levels. Hypotony (I.O.P. < 6 mmHg) was seen more commonly after intraoperative 5-FU (27.3%). Corneal epithelial defects were seen exclusively in the postoperative 5-FU group (40%). The use of intraoperative 5-FU exclusively as a mode of antimetabolite delivery seems an acceptable alternative to enhance success rates of trabeculectomy for the primary glaucomas.

Results of intraoperative 5-fluorouracil in patients undergoing trabeculectomy--pilot trial.

To study the effect of 5-Fluorouracil (5-FU) in glaucoma filtration surgery, 13 eyes of 12 patients with glaucoma were subjected to trabeculectomy with intraoperative one minute exposure of 50 mg/ml 5-FU. The average age of patients was 36.42 +/- 18.78 years. Two of the patients had developed hypotony in the fellow eye following the use of Mitomycin C with trabeculectomy. The mean follow-up period was 9.54 +/- 5.17 weeks. Two patients developed a shallow anterior chamber with choroidals postoperatively which responded to conservative treatment. One patient developed an encysted bleb one month after surgery. Single one minute intraoperative exposure to 5-FU is a convenient and inexpensive method which appears to have no significant side effects. It may be a useful adjunctive treatment to optimise the results of glaucoma filtration surgery particularly in young and myopic patients. The long term effects, however, are not known.