Mitomycin C in the endoscopic treatment of tracheal stenosis: a prospective cohort study / Mitomicina C no tratamento endoscópico de estenose traqueal: estudo prospectivo de coorte

ABSTRACT Objective: To evaluate the efficacy of mitomycin C (MMC) in the endoscopic treatment of tracheal stenosis. Methods: Patients with laryngotracheal, tracheal, or tracheobronchial stenosis were treated with dilation and topical MMC. The inclusion criteria were as follows: being ineligible for surgery (for medical reasons) at the time of evaluation; membranous stenosis responding well to dilation; and postoperative stenosis at the anastomosis site. Etiology of stenosis and indication for treatment with MMC, as well as site, length, and percentage of stenosis, together with presence of tracheostomy and duration of follow-up, were analyzed. The outcomes evaluated were symptom-free interval ≥ 12 months, number of dilations with topical application of MMC, and complications. Results: Twenty-two patients (15 men and 7 women) were treated between 2003 and 2010. Stenosis was due to endotracheal intubation in 15 patients and surgery in 8. Pure tracheal stenosis was encountered in 13 patients, subglottic stenosis was encountered in 4, tracheobronchial stenosis was encountered in 3, and complex stenosis was encountered in 2. The length of stenosis ranged from 0.5 cm to 2.5 cm, and the percentage of stenosis ranged from 40% to 100%. Nine patients had undergone tracheostomy and had a Montgomery T-tube in situ. Treatment was successful in 14 patients, who remained free of symptoms for at least 12 months. The number of topical applications of MMC ranged from 1 to 5, and complications included fungal infection, keloid scarring, granuloma, and mediastinal emphysema. Conclusions: MMC appears to be effective in the endoscopic treatment of tracheal stenosis.

RESUMO Objetivo: Avaliar a eficácia da mitomicina C (MMC) no tratamento endoscópico de estenose traqueal. Métodos: Pacientes com estenose laringotraqueal, traqueal ou traqueobrônquica foram tratados por meio de dilatação e MMC tópica. Foram empregados os seguintes critérios de inclusão: pacientes inaptos para cirurgia (por motivos médicos) no momento da avaliação; estenose membranosa com boa resposta a dilatação e estenose pós-operatória no local da anastomose. Foram analisadas as seguintes variáveis: etiologia da estenose; indicação de tratamento com MMC; local e extensão da estenose, bem como a porcentagem de estenose; presença de traqueostomia e tempo de seguimento. Os desfechos avaliados foram 12 meses ou mais sem sintomas, número de dilatações com aplicação de MMC tópica e complicações. Resultados: Vinte e dois pacientes (15 homens e 7 mulheres) foram tratados entre 2003 e 2010. As causas da estenose foram intubação endotraqueal em 15 pacientes e cirurgia em 8. A estenose traqueal pura foi observada em 13 pacientes, a subglótica, em 4, a traqueobrônquica, em 3 e a complexa, em 2. A extensão da estenose variou de 0,5 a 2,5 cm, e a porcentagem de estenose variou de 40 a 100%. Nove pacientes haviam sido submetidos a traqueostomia e apresentavam tubo T de Montgomery in situ. O tratamento teve êxito em 14 pacientes, que permaneceram sem sintomas durante pelo menos 12 meses. O número de aplicações de MMC tópica variou de 1 a 5, e as complicações foram infecção fúngica, queloide, granuloma e enfisema mediastinal. Conclusões: A MMC é aparentemente eficaz no tratamento endoscópico de estenose traqueal.

A Comparative Study of Topical Mitomycin C, Cyclosporine, and Bevacizumab after Primary Pterygium Surgery

PURPOSE: To compare the recurrence rates and complications associated with instillation of topical mitomycin C, cyclosporine, and bevacizumab after primary pterygium surgery. METHODS: Between July 2013 and June 2014, we performed surgery using the bare sclera method on 132 eyes (132 patients) with primary pterygium. We randomly selected 33 eyes (33 patients) and treated them with artificial tears four times a day for three months, 29 eyes (29 patients) were treated with topical 0.02% mitomycin C four times a day for five days, 34 eyes (34 patients) were treated with topical 0.05% cyclosporine four times a day for three months, and 36 eyes (36 patients) were treated with topical 2.5% bevacizumab four times a day for three months after surgery. We prospectively determined the recurrence rates of pterygium and complications at the six-month follow-up examination. RESULTS: At six months after surgery, the recurrence rates in each group were as follows: 45.5% (15 eyes) in the control group, 10.3% (three eyes) in the mitomycin C group, 20.6% (seven eyes) in the cyclosporine group, and 41.7% (15 eyes) in the bevacizumab group (p = 0.004). No serious complications, except subconjunctival hemorrhages, were observed in any group. CONCLUSIONS: Groups receiving topical 0.02% mitomycin C and 0.05% cyclosporine after surgery showed lower recurrence rates than the control group; however, no difference in recurrence rate was observed between the control group and the group receiving topical 2.5% bevacizumab after surgery.

Comparison of the Outcome of Repeat Trabeculectomy with Adjunctive Mitomycin C and Initial Trabeculectomy

PURPOSE: To compare the efficacy and safety of repeat and initial trabeculectomy with mitomycine C (MMC). METHODS: Eighty seven patients, who had underwent repeat (repeat group) or initial (initial group) trabeculectomy with MMC, were enrolled in this prospective trial. Postoperative outcome measures included the amount of decrease in intraocular pressure (IOP), the number of anti-glaucoma medications, and the complications. The success of trabeculectomy was defined on the basis of three definitions which were: IOP or =30% (definition 3). Success was further defined as "complete" when these criteria were obtained without any anti-glaucoma medications and "qualified" with or without medical therapy and no further surgical procedures. RESULTS: Fifty nine eyes underwent initial and 28 eyes underwent repeat trabeculectomy. The mean follow-up period was 19.1 +/- 5.9 months. Complete success rates were significantly greater in the initial trabeculectomy group (p = 0.02 for definition 1, p = 0.038 for definition 2, p = 0.003 for definition 3). A higher proportion of eyes in the initial group achieved qualified success relative to the group A eyes, but the differences were not statistically significant (p = 0.33 for definition 1, p = 0.99 for definition 2, p = 0.24 for definition 3). The mean number of antiglaucomatous medications at the last examination was 1.2 +/- 1.2 in repeat group and 0.7 +/- 1.1 in initial group (p = 0.01). The number of complications during the follow up period did not differ significantly between the two groups (p = 0.65). CONCLUSIONS: Repeat trabeculectomy with MMC has high success and low complication rates in patients with previously failed trabeculectomy in spite of the need of higher number of anti-glaucoma medications.

Ceratectomia fotorrefrativa com mitomicina-C personalizada pela frente de onda corneana para o tratamento de hipermetropia após ceratotomia radial / Corneal wavefront-guided photorefractive keratectomy with mitomycin-C for consecutive hyperopia after radial keratotomy

OBJETIVO: Avaliar a eficácia, previsibilidade e estabilidade da ceratectomia fotorrefrativa (PRK) guiada pela frente de onda corneana para o tratamento da hipermetropia secundária à ceratotomia radial. MÉTODOS: Este estudo prospectivo analisou 60 olhos de 36 pacientes consecutivos, submetidos a PRK personalizado com o laser Esiris-Schwind. A técnica constou de desepitelização mecânica, fotoablação e utilização de mitomicina-C 0,02 por cento. Os pacientes foram acompanhados por 12 meses. RESULTADOS: O intervalo médio entre a ceratotomia radial e o PRK foi de 18,4 anos ± 3,8 (DP); o equivalente esférico (EE) médio antes da ceratotomia radial era -4,35 dioptrias (D) ± 1,55. As medidas prévias ao PRK mostraram grau esférico médio de +5,00 D ± 2,28, astigmatismo médio de -1,47 D ± 1,06, EE médio de +4,27 D ± 2,18 e AV corrigida (AVcc) média de 0,174 ± 0,139 (logMAR). O EE médio programado no laser foi +4,74 D ± 2,11. Os resultados encontrados um ano após a cirurgia foram: EE médio de +0,04 D ± 1,03 (P<0,001), astigmatismo médio de -1,03 ± 0,75 D (P=0,015), AV média sem correção de 0,265 ± 0,197 e AVcc de 0,079 ± 0,105 (P<0,001). A AVcc mostrou ganho médio de uma linha; 20 olhos (33,3 por cento) melhoraram duas ou mais linhas e somente um olho perdeu duas linhas. Ocorreu redução estatisticamente significante do coma (P=0,002), trefoil (P=0,004), aberração esférica (P<0,001) e quatrefoil (P=0,002). Houve 48 olhos (80 por cento) entre ± 1,00 D do EE planejado. A regressão média entre seis e 12 meses foi de +0,17 ± 0,67 D. CONCLUSÃO: O PRK personalizado pela frente de onda corneana foi eficaz, previsível e estável pelo período de um ano para a redução da hipermetropia após a ceratotomia radial. No pós-operatório, observou-se melhora significativa da AVsc, AVcc e das aberrações corneanas. Número do ClinicalTrials.gov:NCT00917657

PURPOSE: To assess the efficacy, predictability and stability of corneal wavefront-guided photorefractive keratectomy (PRK) for correcting hyperopia and astigmatism after radial keratotomy. METHODS: In a prospective study, 60 eyes of 36 consecutive patients were treated with corneal wavefront-guided PRK with 0.02 percent mitomycin-C using an Esiris-Schwind excimer laser. Corneal epithelium was mechanically removed. All patients were followed-up for 12 months. RESULTS: The mean time between radial keratotomy and PRK was 18.4 years ± 3.8 (SD); mean spherical equivalent (SE) before radial keratotomy was -4.35 diopters (D) ± 1.55. Before PRK, the mean sphere was +5.00 D ± 2.28, mean astigmatism was - 1.47 D ± 1.06, mean SE was +4.27 D ± 2.18, and the mean best-corrected visual acuity (BCVA) was 0.174 ± 0.139 (logMAR). The planned laser SE correction was +4.74 D ± 2.11. No intraoperative complications were noted. At 12 months, mean SE was +0.04 D ± 1.03 (P<0.001), mean astigmatism was -1.03 ± 0.75 D (P=0.015), mean UCVA was 0.265 ± 0.197, and mean BCVA was 0.079 ± 0.105 (P<0.001). There was a mean gain of 1 line of BCVA and 20 eyes (33.3 percent) gained 2 or more lines. Only one eye lost 2 lines. A significant decrease in coma (P=0.002), trefoil (P=0.004), spherical aberration (P<0.001) and quatrefoil (P=0.002) was observed. Forty eight eyes (80 percent) were within ± 1.0 D of intended SE. Mean regression from 6 to 12 months was +0.17 ± 0.67 D. CONCLUSION: Corneal wavefront-guided PRK was effective, predictable and stable after one year of follow-up for the treatment of hyperopia after radial keratotomy. A significant improvement in UCVA, BCVA and corneal aberrations was obtained. ClinicalTrials.gov Identifier: NCT00917657

Miringotomia pelo método de microeletrocautério por radiofrequência associado à mitomicina C em modelo animal / Mitomycin C-associated radiofrequency microelectrocautery used in myringotomy in an animal model

Este estudo tem como objetivo descrever uma técnica cirúrgica alternativa à inserção do tubo de ventilação na membrana timpânica: a miringotomia por radiofrequência isolada e associada à mitomicina C. Objetivo: Demonstrar um método cirúrgico que proporcione uma execução mais simples, não sujeito às complicações vinculadas ao tubo de ventilação. Material e métodos: Foram comparadas as técnicas de miringotomia por microlanceta e por microeletrocautério por radiofrequência (ponteira 0,3mm e 0,7mm) isolada e associada à mitomicina C, considerando o tempo de fechamento timpânico, em ratos da linhagem Wistar. Estudo experimental. Resultados: Houve uma diferença estatisticamente significante entre a miringotomia por radiofrequência e por microlanceta. Ao analisar a técnica por radiofrequência com ponteira 0,7mm associada à mitomicina C (teste de Wilcoxon), o P encontrado foi menor que 0,001, demonstrando uma significância estatística. O tempo máximo de fechamento foi de 44 dias e a mediana encontrada foi de 14 dias. Conclusão: A técnica de miringotomia por radiofrequência (com ponteira de maior diâmetro) associada à mitomicina C, apresenta uma otimização no tempo de cicatrização da mesma.

This study aimed at describing an alternative surgical technique to the insertion of a ventilation tube in the tympanic membrane: myringotomy by radiofrequency alone and associated with mytomicin C. AIM: to show a surgical approach that can be simple to execute, not subject to complications arising from the ventilation tube. Materials and methods: we compared myringotomy by microknife and by radiofrequency microcautery (0.3 mm and 0.7 mm tips) alone and associated with mytomicin C, considering the time of tympanic closure in Wistar rats. Experimental study. Results: there was a statistically significant difference between radiofrequency myringotomy and knife myringotomy. As we analyze the radiofrequency approach with the 0.7mm tip associated with mytomicin C (Wilcoxon test), the p value found was lower than 0.001, showing a statistical significance. The maximum tympanic membrane closure time was 44 days and the median found was 14 days. Conclusion: the radiofrequency myringotomy (with the larger diameter tip) associated with mytomicin C enhances the tympanic membrane healing time.

Ocular decompression retinopathy after trabeculectomy with mitomycin-C for angle recession glaucoma.

A 45-year-old male presented with intractable glaucoma following 360-degree angle recession after blunt trauma. He underwent an uncomplicated trabeculectomy with mitomycin-C (MMC). Adequate precautions were taken to reduce the chances of sudden lowering of intraocular pressure (IOP). He did not have any intraoperative shallowing of the anterior chamber or postoperative hypotony, but still developed ocular decompression retinopathy. On detailed review of the previously reported cases we discovered that besides a large IOP drop after surgery, either the preoperative rise of IOP in all these cases was over a relatively short period or the course of their glaucomatous process was likely to have exposed them to intermittent spikes of high IOP. To our knowledge this factor has not been previously postulated in the pathophysiology of ocular decompression retinopathy. We illustrate this with a rare case of ocular decompression retinopathy after trabeculectomy with MMC for post-traumatic angle recession glaucoma.

Avaliação da cicatrização de feridas em dorso de ratos tratados com mitomicina C tópica e posterior reforço com injetável / Study of wound healing in rats treated with topical and injected mitomycin-C

Estudo experimental em animais. A mitomicina C vem sendo usada como inibidor de fibroblastos, acarretando, com isso, diminuição do processo cicatricial em feridas cirúrgicas. OBJETIVO: Este trabalho visa avaliar o uso de Mitomicina C para diminuir o processo cicatricial, através de seu uso tópico com reforços posteriores injetáveis. MATERIAL E MÉTODOS: Foi usado um modelo de feridas em dorso de ratos, com retirada circular da pele e cicatrização por segunda intenção. Foram usados 18 ratos, divididos em três grupos: controle; com uso tópico; e com reforço de mitomicina C injetável, mensalmente e por 2 meses. Após 3 meses os animais foram sacrificados e as cicatrizes retiradas cirurgicamente e submetidas a estudo histológico. RESULTADOS: Notou-se sob vários critérios que a cicatrização com o uso tópico é menos intensa, mas ao se usar o reforço injetável os parâmetros voltam a ser comparados ao do grupo controle. DISCUSSÃO: Acreditamos que a administração injetável de mitomicina C nas cicatrizes, pela sua elevada característica tóxica, acarreta destruição tecidual e neoformação cicatricial. CONCLUSÕES: A mitomicina C diminui o processo cicatricial quando usada topicamente, mas acarreta aumento da cicatrização quando nestas feridas são feitos reforços injetáveis.

Experimental study in animals. Introduction: Mitomycin C has been used as a fibroblasts inhibitor, thus reducing the scaring process in surgical wounds. AIM: This paper aims at assessing the use of Mitomycin C to reduce the scaring process through its topical use and later injected reinforcements. MATERIALS AND METHODS: We used a model of a creating a wound in the dorsum of rats, removing a circular piece of skin and letting it heal by itself. We used 18 rats, divided in three groups. The first group - Control, the second with topical use, and a third group with injected mitomycin C reinforcement, monthly for 2 months. After 3 months the animals were slaughtered and the scars were surgically removed and sent for histology study. RESULTS: We noticed, under different criteria, that healing with topical mitomycin is less intense; however, when it was injected, the parameters were again comparable to those from the control group. DISCUSSION: We believe that injected mitomycin C in the scar, since it is highly toxic, it destroys tissue and brings about scar neoformation. CONCLUSIONS: Mitomycin C reduces the scaring process when used topically; however, it increases scar tissue formation when injected in these wounds.

Efeito da mitomicina C tópica na cicatrização de prega vocal em modelo suíno / Topical mitomycin C effect on swine vocal folds healing

Várias terapias adjuvantes à cirurgia vêm sendo usadas para modular o processo cicatricial nas pregas vocais, entre elas a Mitomicina tópica (MTC). OBJETIVOS: Avaliar os efeitos da MTC no processo de cicatrização de pregas vocais de suínos 30 dias após exérese de fragmento de mucosa com laser de CO2 mediante a mensuração da deposição de colágeno. FORMA DE ESTUDO: Experimental em suínos. MATERIAIS E MÉTODOS: Dois grupos de 6 suínos cada foram avaliados após exérese de fragmento de mucosa de prega vocal a laser de CO2 (grupo controle sem uso e grupo experimento com uso de MTC tópica). Após 30 dias os animais foram submetidos à eutanásia, sendo coletadas amostras das pregas vocais para análise histológica, a fim de quantificar a deposição de colágeno mediante coloração de Picrosirius Red. RESULTADOS: A média da área do colágeno total das pregas vocais do grupo controle foi de 2648,03 æm2, enquanto a média do colágeno total das pregas vocais do grupo experimento foi de 2200,30 æm2 (p = 0,0043). CONCLUSÃO: A MTC usada topicamente após a exérese de fragmento de mucosa da prega vocal a laser de CO2 em suínos, diminui, significativamente, a deposição do colágeno total.

several adjuvant therapies to surgery have been used to modulate the healing process of vocal folds, including topic mitomycin (MTC). AIM: to evaluate the effect of topical MTC in the healing process of vocal folds 30 days after the exeresis of a mucosal fragment with CO2 laser in a swine model (control group without mitomycin and study group with topical MTC), with collagen deposition measurement. STUDY TYPE: prospective experimental in swine. METHODS: two groups of 6 swine each were subjected to exeresis of a mucosal fragment of the vocal fold with CO2 laser. Immediately after the procedure MTC was applied topically for three minutes on the study group. Thirty days later the animals were slaughtered and samples of the vocal folds were collected for histological analysis, with the purpose of quantifying collagen deposition by Picrosirius Red stain. RESULTS: the average area of total collagen in the vocal folds in the control group was 2.648,03 æm2, whereas in the study group it was 2.200,30 æm2 (p = 0.0043). CONCLUSION: topical application of MTC after the exeresis of a mucous fragment of vocal fold with CO2 laser in swine significantly decreased total collagen deposition.

Intraoperative application of topical mitomycin C 0.05 for pterygium surgery

BACKGROUND: Pterygium recurrence is a common problem encountered by ophthalmic surgeons. Several methods have been suggested to avoid these recurrences. We studied the recurrence rate of pterygium after administration of a single intraoperative dosage of topical mitomycin C 0.05. METHODS: A retrospective analysis of fifty eyes in forty-nine patients who underwent pterygium excision by the same surgeon using intraoperative topical mitomycin C during the years 2002--2003. Mitomycin concentration was 0.05 applied to pterygium and adjacent areas after undermining and separation from sclera but prior to excision for three minutes. Postoperative follow up time was 12 months. RESULTS: The pterygium recurred in 4 (8) eyes. Another four eyes (8) had a cosmetically acceptable recurrence of < 2.0 mm. The only complication was a corneal dellen in one eye. CONCLUSION: Intraoperative administration of mitomycin C at 0.05 is safe and effective in preventing pterygium recurrences

Carcinoma de células escamosas em língua pós-transplante de medula óssea por Anemia de Fanconi / Squamous cell carcinoma of the tongue due to Fanconi's Anemia after bone marrow transplantation

Anemia Fanconi (AF) é uma síndrome autossômica recessiva, caracterizada por pancitopenia progressiva com hipoplasia de MO, em associação com várias anormalidades constitucionais, tendo como único recurso terapêutico com possibilidade potencial de cura o transplante de medula óssea, e sendo tais pacientes propensos ao desenvolvimento de malignidades hematológicas e carcinoma de células escamosas (CEC) em diversos locais: reto, vagina, cérvice, esôfago, cavidade bucal, faringe ou pele, mas especialmente em cabeça e pescoço. Relatamos aqui três casos de pacientes portadores de AF, que após TMO desenvolveram CEC em língua. Além disso, mencionamos fatores de risco relatados para tal evento, como diagnóstico de AF, condicionamento pré-transplante (quimioterápicos e irradiação), terapia com drogas imunossupressoras para tratamento de doença enxerto contra hospedeiro (DECH) aguda ou crônica, sexo e idade avançada. Além do que, discorremos sobre a existência de três mecanismos postulados que predispõem indivíduos com AF ao desenvolvimento de neoplasia: (1) defeito na reparação do DNA; (2) defeito na detoxificação de radicais de oxigênio; e (3) imunodeficiência.

Fanconi’s Anemia, first described in 1927, is a rareautonomic recessive disease characterized byprogressive pancytopenia, congenital malformations,spontaneous or chemically induced chromosomebreakage and increased incidence of leukemia andother cancers. The onset of bone marrow hypoplasiaand its hematological manifestations is usually in the3 - 7 year age range. Additionally, we discussed the existence ofthree postulated mechanisms that make individualswith Fanconi’s anemia susceptible to the developmentof neoplasias: (1) deficiency in the DNA repair system,(2) deficiency in oxygen radical detoxification; and(3) immunodeficiency.

Caffeine, quercetin and alizarin stimulate the exhalation of metabolic products of [14C]-N-nitrosodiethylamine in mice.

Naturally occurring plant products belonging to different chemical classes namely alizarin, an anthraquinone, caffeine, a methylxanthine derivative and quercetin, a flavonol were studied for their effect on elimination of metabolites of [14C]-N-nitrosodiethylamine (14C-NDEA) through respiration in mice. Treatment with caffeine, quercetin and alizarin at doses of 200, 9 and 9 microg/ml respectively, in drinking water enhanced the exhalation of 14CO2, one of the major end products of NDEA metabolism. Radioactive CO2 exhaled in 60 min increased by 2, 1.61 and 1.4-folds in animals treated with caffeine, quercetin and alizarin for 8 weeks respectively. This increase in exhalation in caffeine-treated animals was achieved even in 2 weeks. These compounds had no adverse effects on the absorption of radioactive NDEA from the gut of the animals as shape and time of 14CO2 peak was similar in i.p. and orally administered [14C-NDEA]. Increased detoxification/elimination of the carcinogen could be one of the mechanisms for the anticarcinogenic properties of these phytochemicals in lung tumorigenesis induced by orally administered NDEA.

Assessing the role of subconjunctival versus intrascleral application of mitomycin C in high-risk trabeculectomies.

PURPOSE: To compare the efficacy and safety of subconjunctival and intrascleral applications of mitomycin C (MMC) in trabeculectomy for high-risk glaucomas. METHODOLOGY: A randomized prospective clinical study was conducted on 41 consecutive eyes with a high risk of glaucoma surgery failure. Patients were randomized to trabeculectomy and application of subconjunctival MMC or to trabeculectomy and application of intrascleral MMC. MMC solution 0.2 mg/ml was applied for 3 minutes under the conjunctival flap overlying the proposed site of trabeculectomy in Group I (n=21), or intrasclerally under the superficial scleral flap in Group II (n=20) RESULTS: After a follow-up of one year, the intraocular pressure (IOP) decreased from a mean basal IOP of 33.0 +/- 8.4 mm Hg to 12.56 +/- 2.54 mm Hg in Group I and from 30.9 +/- 6.6 mm Hg to 11.6 +/- 2.21 mm Hg in Group II. The IOP was 6-21 mmHg, without medication, in 90.5 % of the eyes in Group I and 75 % of the eyes Group II. Ocular hypotony, hypotony maculopathy, choroidal detachment and a shallow anterior chamber were more frequent with the intrascleral application of MMC during trabeculectomy, but the difference was not statistically significant. The overall success of the surgery at one year, i.e., achieving an IOP of 6-21 mmHg and a stable vision, (reduction in visual acuity of < or = 2 lines), was 90.5% in Group I and 75 % in Group II. CONCLUSION: No significant difference was seen in overall success or complication between subconjunctival and intrascleral application of MMC-augmented trabeculectomies in glaucomatous eyes at high risk of surgical failure.

Granulomatose de Wegener: aspectos clínicos e terapêuticos / Wegener's granulomatosis: clinical aspects and therapeutics

A granulomatose de Wegener constitui-se em uma vasculite granulomatosa necrosante que acomete vários sistemas orgânicos, notadamente o trato respiratório e os rins. Possui etiologia desconhecida, provavelmente relacionada à hipersensibilidade a antígenos inalados causadores de infecçäo. Estes agentes parecem estimular a produçäo de auto-anticorpos contra antígenos no citoplasma de neutrófilos. Clinicamente, surge em torno da quarta e quinta décadas, através de um quadro de sinusite associado a sintomas constitucionais como febre, fadiga e mal-estar geral. Este quadro inespecífico dificulta o diagnóstico precoce, possibilitando o desenvolvimento de doença disseminada. A clínica do órgäo acometido, associada à presença do anticorpo antineutrofílico citoplasmático (c-ANCA) e os achados anatomopatológicos confirmam o diagnóstico de doença ativa. O tratamento é feito através da associaçäo de corticóides e ciclofosfamida, o que possibilita o controle da doença a curto e médio prazo. As recidivas säo ainda freqüentes, podendo ocorrer em até 20 anos após o início do tratamento.

Midterm follow-up of necrotic bleb excision and advancement of the fornical conjunctiva

Mitomycin C has improved the success rate of glaucoma filtering surgery in patients at high risk for surgical failure. However chronic hypotony is marked by decreased vision and a late-onset leaking bleb after filtration surgery using mitomycin C. Bleb excision and conjunctival advancement is the method of choice to repair bleb leakage and chronic hypotony. Five eyes from five patients were received glaucoma filtration surgery with topical mitomycin C. All of the patients' blebs were avascular and transparent. The reasons for bleb excision were two spontaneous bleb leaks, two traumatic bleb leaks and one case of severe irritation. The mean follow-up period was 18.4 +/- 8.3 months (ten to 29 months). Cataract surgery was combined in one eye. Postoperative intraocular pressure (IOP) increased from 2.3 +/- 1.5 mmHg to 9.5 +/- 3.7 mmHg at nine months postoperatively in four eyes. It went from 28 mmHg to 40 mmHg in one patient with uveitis, for whom a second trabeculectomy with mitomycin C; 0.4 mg/ml for 3 minutes, was performed. After surgery, IOP decreased to 4 mmHg in three months. Postoperative visual acuity improved four snellen lines in three eyes. A partially avascular bleb recurred in three eyes, a corneal bleb in one eye and blepharoptosis, which disappeared spontaneously at four months postoperatively, in one eye. Necrotic bleb excision and advancement of fornical conjunctiva were useful methods to increase IOP and to improve visual acuity for the patient experiencing irritation symptoms, and for leaking blebs, and hypotonic maculopathy.

Adaptive response to low dose of EMS or MMS in human peripheral blood lymphocytes.

Human peripheral blood lymphocytes stimulated in vitro for 6 hr were exposed to a low (conditioning) dose of ethyl methanesulfonate (EMS; 1.5 x 10(-4) M) or methyl methanesulfonate (MMS; 1.5 x 10(-5) M). After 6 hr, the cells were treated with a high (challenging) concentration of the same agent (1.5 x 10(-3) M EMS or 1.5 x 10(-4) M MMS). The cells that received both conditioning and challenging doses became less sensitive to the induction of sister chromatid exchanges (SCEs) than those which did not receive the pretreatment with EMS or MMS. They responded with lower frequencies of SCEs. This suggests that conditioning dose of EMS or MMS has offered the lymphocytes to have decreased SCEs. This led to the realization that pre-exposure of lymphocytes to low dose can cause the induction of repair activity. This is a clear indication of the existence of adaptive response induced by alkylating agents whether it is ethylating or methylating in human lymphocytes in vitro.