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Treatment of malignant melanoma has improved in the last few years owing to early detection and new therapeutic options. Still, management of advanced disease remains a challenge because it requires systemic treatment. In such cases, dacarbazine-based chemotherapy has been widely used, despite low efficacy. Neoadjuvant therapies emerge as alternative options that could help chemotherapy to achieve increased benefit. In this work, we evaluate LVR01, an attenuated Salmonella enterica serovar typhimurium, as neoadjuvant intralesional therapy in combination with dacarbazine in a preclinical melanoma model. B16F1 melanoma‒bearing mice received intraperitoneal administration of dacarbazine for 3 consecutive days. LVR01 treatment, consisting of one single intratumoral injection, was applied 1 day before chemotherapy began. This therapeutic approach retarded tumor growth and prolonged overall survival, revealing a strong synergistic antitumor effect. Dacarbazine induced a drastic reduction of secondary lymphoid organ cellularity, which was partially restored by Salmonella, particularly potentiating activated cytotoxic cell compartments. Systemic immune reactivation could be a consequence of the intense inflammatory tumor microenvironment induced by LVR01. We propose that the use of LVR01 as neoadjuvant intralesional therapy could be considered as an interesting strategy with close clinical application to boost chemotherapy effect in patients with melanoma.

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The role of circumcision in partially protecting against sexually transmitted infections (STIs) and other dermatoses has been documented. Neonatal circumcision is not routinely practiced in South America. Although it is logical to assume that male genital dermatoses are more prevalent in Hispanic men, they are underrepresented in the existing literature. Objective: To describe the epidemiological characteristics from our male genital dermatology unit in Montevideo (Uruguay), the diagnoses, and correlate them with circumcision status and comorbidities. Methods: A retrospective observational cohort study was conducted. A dermatologist and urologist evaluated all patients using standard questionnaires. In 3 years and 8 months, 269 patients were seen. Median age was 41, prevalence of neonatal circumcision was 0.7%, HIV was 4.2%, STIs were 24.9%, non-STIs were 63.9%, and both (STI + non-STI) were 11.2%. Most frequent entities: eczema/balanoposthitis (27.1%), condyloma (24.9%), and lichen sclerosus (15.6%). Data correlating circumcision and other diagnoses did not reach statistical significance. HIV was positively associated with other STIs (p < 0.05), and an association with balanoposthitis was seen; however, it did not reach statistical significance (p < 0.1). Main limitation was small sample size. This is the first study of its kind based on Hispanic patients. Collaboration between specialties proved to be fundamental. Further studies are needed in this demographic to find an association between circumcision, comorbidities, and genital dermatoses.

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Penile sclerosing granuloma is a foreign body reaction to the injection of material, usually for genital augmentation purposes. Patients commonly deny having had or performed these procedures on themselves, and diagnosis can be challenging. We describe the case of a 62-year-old man with a 10-year history of a growth on the penile shaft. Dermoscopic examination showed an orange background with shiny white structures, suggesting a granulomatous pathology. Guided biopsies confirmed a sclerosing lipogranuloma. The patient admitted to having self-injected motor oil. For the first time, we report the dermoscopic description of sclerosing granuloma, which will improve clinical diagnostic precision and guide biopsies. We also contribute the first description of a dermoscopic rainbow pattern in a granulomatous disorder; this could be due to a physical phenomenon called 'dichroism'.

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Ultrapotent topical corticosteroids and circumcision are usually effective for male genital lichen sclerosus (MGLSc); however, refractory cases are often referred to our Male Genital Dermatology Unit. Treatment with autologous platelet-rich plasma (TPRP) has recently been advocated as a safe and effective treatment option, but there have been no prospective studies in men to date. The objective of this study is to assess the safety and efficacy of TPRP for MGLSc resistant to conventional therapy. A prospective, open-label, single-arm, therapeutic study was carried out in this study. Inclusion criteria: resistant to conventional therapy for at least 6 months. Procedure: infiltration of 0.1 mL/cm2 PRP every 8 weeks. Monthly data recording: visual appearance with photographs and external scoring by an expert using Investigator's Global Assessment Scale (IGA scale 0-5), symptoms (scale 0-5), quality of life (QoL; Dermatology Life Quality Index [DLQI]), and complications. No. of patients included was n = 5. No. of patients excluded during treatment was n = 1. Mean initial IGA: 3.6. Mean initial DLQI: 6. TPRP n = 34 (range: 2-9; average: 6.8 per patient). Mean IGA at 18 months: 3.25. Mean DLQI at 18 months: 1.25. All patients reported being completely asymptomatic at 10 months. No. of patients with complications is n = 1 (balanitis). TPRP seems to be safe and effective, regarding symptom control and improvement in QoL; however, visual changes were minimal.

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Cellular senescence is an endpoint of chemotherapy, and targeted therapies in melanoma and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and an enhanced mitochondrial energy metabolism supports resistance to therapy in melanoma cells. Herein, we assessed the mitochondrial function of therapy-induced senescent melanoma cells obtained after exposing the cells to temozolomide (TMZ), a methylating chemotherapeutic agent. Senescence induction in melanoma was accompanied by a substantial increase in mitochondrial basal, ATP-linked, and maximum respiration rates and in coupling efficiency, spare respiratory capacity, and respiratory control ratio. Further examinations revealed an increase in mitochondrial mass and length. Alterations in mitochondrial function and morphology were confirmed in isolated senescent cells, obtained by cell-size sorting. An increase in mitofusin 1 and 2 (MFN1 and 2) expression and levels was observed in senescent cells, pointing to alterations in mitochondrial fusion. Silencing mitofusin expression with short hairpin RNA (shRNA) prevented the increase in mitochondrial length, oxygen consumption rate and secretion of interleukin 6 (IL-6), a component of the SASP, in melanoma senescent cells. Our results represent the first in-depth study of mitochondrial function in therapy-induced senescence in melanoma. They indicate that senescence increases mitochondrial mass, length and energy metabolism; and highlight mitochondria as potential pharmacological targets to modulate senescence and the SASP.

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BACKGROUND: Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow-derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs. METHODS: We conducted an open-label, single-arm, prospective pilot clinical trial in four patients with six chronic VLUs. The study protocol was approved by the institutional and national review boards and ethics committees. Bone marrow was harvest, processed and then administered by multiple injections into the ulcers. All patients received standard treatment and non-healing characteristics of the VLUs were confirmed at study entry. RESULTS: Ulcer size and wound pain evaluated 12 months after BMDC treatment were significantly reduced (P < 0.05). BMDC treatment was safe and well tolerated in long-term follow-up. DISCUSSION: Despite the low number of patients studied, our results showed that autologous BMDC treatment could be a useful, feasible and safe procedure to enhance ulcer healing. However, randomized controlled trials with more patients are needed to address this question and translate this approach into clinical practice.

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RESUMEN: Introducción: Independientemente de su etiología, las heridas crónicas, representan un desafío terapéutico debido a que muchas veces son refractarias a tratamientos convencionales. Es por este motivo que en los últimos años se han desarrollado de forma creciente estrategias complementarias en el área de la medicina regenerativa, como: terapias con células madre, ingeniería de tejidos, plasma rico en plaquetas y factores de crecimiento aplicados en las heridas crónicas. Dichas terapias complementarias han mostrado ciertos beneficios en la cicatrización de heridas complejas. Materiales y métodos: Se presentan dos casos clínicos de pacientes con heridas crónicas de diferente etiología, refractarias al tratamiento con cura avanzada de heridas, las cuales recibieron de forma complementaria factor estimulante de colonias de granulocitos (G-CSF; Filgen®). Se realizaron inyecciones locales de G-CSF a una dosis de 300 mcg/ml en piel peri úlcera en forma semanal completando dos series de cuatro inyecciones cada una. Resultados. Ambos casos presentaron una reducción en el área de las mismas alcanzándose la cicatrización total en un paciente y una reducción del 37% en el otro luego de dos series. El procedimiento fue bien tolerado y no se reportaron efectos adversos relacionados al mismo. Conclusiones: Los resultados obtenidos en estos pacientes mostraron beneficios en la cicatrización con la aplicación del G-CSF. Se requieren de ensayos clínicos controlados que permitan establecer el rol de dicho factor en el tratamiento de las mismas. Por este motivo nuestro grupo de trabajo se encuentra desarrollando un protocolo que permita evaluar este aspecto.

ABSTRACT: Introduction: Regardless of their etiology, chronic wounds, represent a therapeutic challenge because they are often refractory to conventional treatments. Due to this observation, in the last few years, new complementary strategies have emerged in the area of regenerative medicine, including stem cell therapeutics, tissue engineering, platelet rich plasma, and growth factors applied to chronic wounds. These complementary therapies have shown certain benefits in healing of complex wounds. Materials and methods: We present two clinical cases of patients with chronic wounds of different etiology, refractory to advanced and conventional wound treatments, which received complementary granulocyte colony-stimulating growth factor (G-CSF; Filgen®). Local injections with G-CSF were administered weekly in periulcer skin at a dose of 300 mcg/ml, completing two series of four injections each. Results: Both cases showeda reduction in their areas, reaching to total healing inone patient, and a reduction of 37% in the other one after two series of treatment. The procedure was well tolerated and no adverse effects were detected. Conclusions: The results obtained with these patients showed a benefit in cicatrization with the administration of G-CSF. Controlled clinical trials are needed to establish the role of G-CSF in these wounds. Thus, our group is developing a protocol to evaluate this aspect.

RESUMO: Introdução: Independentemente da sua etiologia, as feridas crônicas representam um desafio terapêutico porque muitas vezes são refratárias aos tratamentos convencionais. É por esta razão que nos últimos anos foram desenvolvidas estratégias complementares na área da medicina regenerativa, tais como: terapias de células estaminais, engenharia de tecidos, plasma rico em plaquetas e fatores de crescimento aplicados a feridas crônicas. Tais terapias complementares mostraram certos benefícios na cicatrização de feridas complexas. Materiais e métodos: Dois casos de pacientes com feridas crónicas de diferentes etiologias, refractárias ao tratamento com a cura da ferida avançado, que receberam complementaria factor estimulante forma de colónias de granulócitos (Filgen® FEC-G) presente. As injeções locais de G-CSF foram feitas a uma dose de 300 mcg / ml na pele peri úlcera, semanalmente, completando duas séries de quatro injeções cada. Resultados: Ambos os casos mostraram uma redução na área do mesmo atingindo a cicatrização total em um paciente e uma redução de 37% no outro após duas séries. O procedimento foi bem tolerado e nenhum efeito adverso relacionado a ele foi relatado. Conclusões: Os resultados obtidos nestes pacientes mostraram benefícios na cura com a aplicação de G-CSF. Ensaios clínicos controlados são necessários para estabelecer o papel desse fator no tratamento deles. Por esse motivo, nosso grupo de trabalho está desenvolvendo um protocolo que nos permite avaliar esse aspecto.

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AIM: We evaluated a novel approach combining the use of attenuated Salmonella immunotherapy with a Toll-like receptor agonist, imiquimod, in B16F1 melanoma-bearing mice. MATERIALS & METHODS: B16F1 melanoma-bearing mice were daily treated with topical imiquimod in combination with one intratumoral injection of attenuated Salmonella enterica serovar Typhimurium LVR01. RESULTS: The combined therapy resulted in retarded tumor growth and prolonged survival. Combination treatment led to an enhancement in the expression of pro-inflammatory cytokines and chemokines in the tumor microenvironment, with a Th1-skewed profile, resulting in a broad antitumor response. The induced immunity was effective in controlling the occurrence of metastasis. CONCLUSION: Salmonella LVR01 immunotherapy in combination with imiquimod is a novel approach that could be considered as an effective antimelanoma therapy.

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BACKGROUND: When possible, surgery is the treatment of choice for cutaneous carcinomas, as it allows to us perform the anatomopathological study and control the surgical margins. Mohs micrographic surgery (MMS) controls 100% of the margins, maintains a larger amount of healthy tissue, and a fewer number of recurrences are seen. Large limb surgical defects after MMS are a challenge. Within the different kind of flaps, the keystone flap, which is a fasciocutaneous island advancement flap, is an option. METHODS: A descriptive study was carried out on the extremity defects that occurred after MMS, which were reconstructed with the modified keystone type flap, during the years 2013-2014 in our department. RESULTS: Six patients underwent reconstruction surgery with the modified keystone flap. The tumor types presented by the patients were four squamous cell carcinomas and two basal cell carcinomas. Locations of the repaired defects were three in the leg, two in the thigh, and one in the forearm. The average size of the repaired defects was 3.1 cm. The procedure was well tolerated in all cases. No complications were observed, such as postoperative bleeding, infection, or necrosis, or dehiscence of the suture. CONCLUSIONS: The modified keystone flap has been very helpful for solving the limb defects of these six patients, although they were not compared with other types of reconstruction.

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BACKGROUND: Chronic venous ulcers (CVU) represent a frequent condition, with difficult therapeutic approaches, that impact on patients’ quality of life, and generate an economic burden to patients and health systems. AIM: To perform the cultural adaptation and initial evaluation of the Charing Cross Venous Ulcer Questionnaire (CCVUQ) for Uruguay, and to study the health-related quality of life (HRQL) of patients with CVU. MATERIAL AND METHODS: The translated and culturally adapted version of the CCVUQ was applied to a convenience sample of 50 patients. In addition, the PROMIS Global Health Survey was included in the assessment. RESULTS: Both questionnaires showed good internal consistency (Cronbach alfa > 0.70). A statistically significant association was observed between the CCVUQ total scores, its subscales and both dimensions of the PROMIS: Global Physical (GPH) and Global Mental Health (GMH) (rho ≥ 0.40). The CCVUQ mean score was 54.9 ± 42 points while GPH and GMH mean scores were 37.9 ± 29 points, and 43.1 ± 35.1 points respectively. Simple linear regression showed that patients with higher income reported better emotional well-being, while in younger patients, ulcers had a higher impact on Emotional Status and Cosmetics. CONCLUSIONS: The translated and adapted version of the CCVUQ was easy to comprehend and apply, showing good psychometric properties. When used in association with the PROMIS Global Health Measure it provides complementary information. HRQL was severely affected in the study sample.

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Background: Chronic venous ulcers (CVU) represent a frequent condition, with difficult therapeutic approaches, that impact on patients’ quality of life, and generate an economic burden to patients and health systems. Aim: To perform the cultural adaptation and initial evaluation of the Charing Cross Venous Ulcer Questionnaire (CCVUQ) for Uruguay, and to study the health-related quality of life (HRQL) of patients with CVU. Material and Methods: The translated and culturally adapted version of the CCVUQ was applied to a convenience sample of 50 patients. In addition, the PROMIS Global Health Survey was included in the assessment. Results: Both questionnaires showed good internal consistency (Cronbach alfa > 0.70). A statistically significant association was observed between the CCVUQ total scores, its subscales and both dimensions of the PROMIS: Global Physical (GPH) and Global Mental Health (GMH) (rho ≥ 0.40). The CCVUQ mean score was 54.9 ± 42 points while GPH and GMH mean scores were 37.9 ± 29 points, and 43.1 ± 35.1 points respectively. Simple linear regression showed that patients with higher income reported better emotional well-being, while in younger patients, ulcers had a higher impact on Emotional Status and Cosmetics. Conclusions: The translated and adapted version of the CCVUQ was easy to comprehend and apply, showing good psychometric properties. When used in association with the PROMIS Global Health Measure it provides complementary information. HRQL was severely affected in the study sample.

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El síndrome de Brooke-Spiegler es una genodermatosis poco frecuente, de transmisión autosómica dominante, que predispone a múltiples tumores anexiales, más comúnmente cilindromas, tricoepiteliomas, espiradenomas. Pacientes con el síndrome de Brooke-Spiegler, cilindromatosis familiar y tricoepitelioma múltiple familiar presentan mutaciones en el gen supresor tumoral CYLD. Actualmente a estas tres entidades se las engloba en el denominado síndrome cutáneo CYLD, ya que representan variaciones fenotípicas de una misma entidad. Presentamos un caso clínico de un hombre de 48 años de edad afectado por el síndrome de Brooke-Spiegler...

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Introducción: en el Centro Hospitalario Pereira Rossell se registró un aumento progresivo de gestantes y recién nacidos (RN) con prueba de detección para sífilis (VDRL) reactivos. Frentea esa situación el Programa Nacional de Salud de la Niñez realizó una investigación para identificar los factores contribuyentes a la ocurrencia de sífilis congénita (SC) medianteauditorías de historias clínicas.Material y método: es un trabajo descriptivo cuya fuente de datos fueron la historia clínica del binomio madre-hijo complementada por el interrogatorio a madres y médicos tratantes. En cuatro meses de auditoría (octubre 2007 - enero 2008) se identificaron a todos los RN con VDRL reactivos y sus madres. La información se incorporó a una base de datos en EpiInfo 6.4. Resultados: se captaron 58 RN correspondientes a 56 madres. Los antecedentes maternospermitieron considerar la reactividad serológica de 12 RN como un recuerdo inmunológico. Diez gestantes infectadas no tuvieron controles prenatales y en otras 12 se comprobó la infección pero no fueron tratadas. Se infectaron o reinfectaron en el último trimestre 24(52,2%) de las gestantes. Relataron episodios de sífilis anteriores 41,9% y problemas tales como abortos, óbitos, bajo peso. Cinco de los RN presentaron manifestaciones clínicas o paraclínicas de SC. Estos y los RN con SC probable recibieron penicilina durante diez días.Los servicios responsables no lograron captar las parejas sexuales y sólo notificaron 44% de las SC.Conclusiones: las auditorías ampliaron la información, evidenciando debilidades en los registros, fallas en los controles prenatales, frecuencia de reinfecciones y subnotificación de los casos de SC.(AU)

Introduction: a progressive increase in VDRL positive pregnant women and newborns was registered at thePereira Rossell Hospital Center. For this reason the Programa Nacional de Salud de la Niñez (Childrenãs Health National Programme) conducted research to identify the factors that contribute to congenital syphilis by auditing medical histories. Method: we conducted a descriptive study based on the information arising from the mother-child binomial medical record and on interviews to mothers and treatingdoctors. For four months (October 2007-January 2008) we identified all VDRL positive newborns and their mothers.Data were analyzed with EpiInfo 6.4. software. Results: we found 58 newborns that corresponded to56 mothers. Maternal precedents led us to consider serologic activity in 12 newborns as an immune memory. Tenpregnant women had no prenatal controls and infection was proved in other 12 women, although they were nottreated. 24 (52.2%) were infected or re-infected in the last trimester. 41.9% informed about previous episodes ofsyphilis and problems such as abortions, fetal death or low weight. Five newborns presented clinical or para-clinical manifestations of congenital syphilis. The latter and the newborns with probable congenital syphilis weretreated with penicillin for ten days. Responsible services failed to reach sexual partners and only reported 44% of congenital syphilis. Conclusions: audits provided more information, evidencing weaknesses in records, failures in prenatal controls, re-infection frequency and the fact that CS is underreported.(AU)

Introdução: no Centro Hospitalar Pereira Rossell foi registrado um aumento progressivo de gestantes e recémnascidos (RN) com exames para diagnóstico de sífilis (VDRL) positivos. Por essa razão o Programa Nacional deSaúde da Criança realizou uma auditoria de prontuários de pacientes para identificar os fatores que favoreciam oaparecimento de casos de sífilis congênita (SC). Material e método: este é um estudo descritivo realizado com dados obtidos dos prontuários de paciente do binômio mãe-filho complementada com perguntas realizadas a mães e médicos. Foram identificados todos os RN com VDRL positivos e suas mães durante os quatro meses de auditoria (outubro 2007 - janeiro 2008). Os dados foram registrados em uma base de dados no programa EpiInfo 6.4. Resultados: foram identificados 58 RN correspondentesa 56 mães. Os antecedentes maternos possibilitaram considerar a reação sorológica de 12 RN como memóriaimunológica. Dez gestantes portadoras de sífilis não haviam realizado controles pré-natais e em outras 12 a infecção foi diagnosticada, porém não foram tratadas. Vinte e quatro gestantes (52,2%) foram infectadas ou reinfectadas no último trimestre de gestação. 41,9% informaram episódios anteriores de sífilis e problemas como abortos, mortes e baixo peso. Cinco RN apresentaram manifestações clínicas ou laboratoriais de SC. Estes RN e os que eram portadores prováveis de SC foram tratados com penicilina durante 10 dias. Os serviços de saúde não puderam captar os parceiros sexuais e somente 44% deles foram notificados.Conclusões: as auditorias permitiram ter acesso a mais informação mostrando debilidades nos registros, falhas nos controles pré-natais, freqüência de reinfecções e subnotificação de casos de SC.(AU)

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Introducción: en el Centro Hospitalario Pereira Rossell se registró un aumento progresivo de gestantes y recién nacidos (RN) con prueba de detección para sífilis (VDRL) reactivos. Frentea esa situación el Programa Nacional de Salud de la Niñez realizó una investigación para identificar los factores contribuyentes a la ocurrencia de sífilis congénita (SC) medianteauditorías de historias clínicas.Material y método: es un trabajo descriptivo cuya fuente de datos fueron la historia clínica del binomio madre-hijo complementada por el interrogatorio a madres y médicos tratantes. En cuatro meses de auditoría (octubre 2007 - enero 2008) se identificaron a todos los RN con VDRL reactivos y sus madres. La información se incorporó a una base de datos en EpiInfo 6.4. Resultados: se captaron 58 RN correspondientes a 56 madres. Los antecedentes maternospermitieron considerar la reactividad serológica de 12 RN como un recuerdo inmunológico. Diez gestantes infectadas no tuvieron controles prenatales y en otras 12 se comprobó la infección pero no fueron tratadas. Se infectaron o reinfectaron en el último trimestre 24(52,2%) de las gestantes. Relataron episodios de sífilis anteriores 41,9% y problemas tales como abortos, óbitos, bajo peso. Cinco de los RN presentaron manifestaciones clínicas o paraclínicas de SC. Estos y los RN con SC probable recibieron penicilina durante diez días.Los servicios responsables no lograron captar las parejas sexuales y sólo notificaron 44% de las SC.Conclusiones: las auditorías ampliaron la información, evidenciando debilidades en los registros, fallas en los controles prenatales, frecuencia de reinfecciones y subnotificación de los casos de SC.

Introduction: a progressive increase in VDRL positive pregnant women and newborns was registered at thePereira Rossell Hospital Center. For this reason the Programa Nacional de Salud de la Niñez (ChildrenÆs Health National Programme) conducted research to identify the factors that contribute to congenital syphilis by auditing medical histories. Method: we conducted a descriptive study based on the information arising from the mother-child binomial medical record and on interviews to mothers and treatingdoctors. For four months (October 2007-January 2008) we identified all VDRL positive newborns and their mothers.Data were analyzed with EpiInfo 6.4. software. Results: we found 58 newborns that corresponded to56 mothers. Maternal precedents led us to consider serologic activity in 12 newborns as an immune memory. Tenpregnant women had no prenatal controls and infection was proved in other 12 women, although they were nottreated. 24 (52.2%) were infected or re-infected in the last trimester. 41.9% informed about previous episodes ofsyphilis and problems such as abortions, fetal death or low weight. Five newborns presented clinical or para-clinical manifestations of congenital syphilis. The latter and the newborns with probable congenital syphilis weretreated with penicillin for ten days. Responsible services failed to reach sexual partners and only reported 44% of congenital syphilis. Conclusions: audits provided more information, evidencing weaknesses in records, failures in prenatal controls, re-infection frequency and the fact that CS is underreported.

Introdução: no Centro Hospitalar Pereira Rossell foi registrado um aumento progressivo de gestantes e recémnascidos (RN) com exames para diagnóstico de sífilis (VDRL) positivos. Por essa razão o Programa Nacional deSaúde da Criança realizou uma auditoria de prontuários de pacientes para identificar os fatores que favoreciam oaparecimento de casos de sífilis congênita (SC). Material e método: este é um estudo descritivo realizado com dados obtidos dos prontuários de paciente do binômio mãe-filho complementada com perguntas realizadas a mães e médicos. Foram identificados todos os RN com VDRL positivos e suas mães durante os quatro meses de auditoria (outubro 2007 - janeiro 2008). Os dados foram registrados em uma base de dados no programa EpiInfo 6.4. Resultados: foram identificados 58 RN correspondentesa 56 mães. Os antecedentes maternos possibilitaram considerar a reação sorológica de 12 RN como memóriaimunológica. Dez gestantes portadoras de sífilis não haviam realizado controles pré-natais e em outras 12 a infecção foi diagnosticada, porém não foram tratadas. Vinte e quatro gestantes (52,2%) foram infectadas ou reinfectadas no último trimestre de gestação. 41,9% informaram episódios anteriores de sífilis e problemas como abortos, mortes e baixo peso. Cinco RN apresentaram manifestações clínicas ou laboratoriais de SC. Estes RN e os que eram portadores prováveis de SC foram tratados com penicilina durante 10 dias. Os serviços de saúde não puderam captar os parceiros sexuais e somente 44% deles foram notificados.Conclusões: as auditorias permitiram ter acesso a mais informação mostrando debilidades nos registros, falhas nos controles pré-natais, freqüência de reinfecções e subnotificação de casos de SC.

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Systemic administration of cytokines has shown therapeutic benefits in cancer patients; however, serious adverse effects associated with direct protein administration prevent the wide use of this approach. We have assessed the capacity of live attenuated Salmonella to act as a vector for oral cytokine-gene therapy. Salmonella orally administered to melanoma-bearing mice was found to accumulate within the tumor, reaching up to 10(5) bacteria per gram of tumor by day 21 after bacterial inoculation. Numbers of bacteria recovered from tumor did not differ from those recovered from liver or spleen at any time point. Recombinant bacteria carrying eukaryotic expression vectors encoding the murine IL-4 or IL-18 genes were administered to groups of mice with established subcutaneous melanoma tumors. We found that a single oral dose of Salmonella carrying any of the cytokine-encoding plasmids resulted in significantly increased survival time, as compared with mice that received Salmonella carrying the parental plasmid or PBS. Increased levels of IFNgamma were found in sera of animals receiving either of the cytokine-encoding bacteria, but not in mice receiving Salmonella alone or PBS. Co-administration of both recombinant bacteria maximized the production of IFNgamma. Overall these results suggest that cytokine-encoding Salmonella can be an effective and safer alternative to systemic administration of cytokines for immunotherapy of cancer.

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We have used Salmonella as a delivery system for eukaryotic expression plasmids encoding cytokines, and assessed its capacity to modulate immune responses in different experimental models. Plasmids encoding mouse IL-4 and IL-18 under cytomegalovirus promoter were constructed and transformed into live attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA, and Salmonella enterica serovar Typhimurium strain SL3261. We have shown that systemic as well as mucosal immunization with such constructs can influence the antibody and cytokine responses to the Salmonella carrier and to co-administered bystander antigens, as well as the specific immune response elicited during a parasitic infection. Further, we have shown that oral cytokine-therapy using Salmonella as gene vector induce antitumoral effect as demonstrated by extended survival time in melanoma-bearing mice. This approach may be particularly suited for the development of new immunotherapies with applications in parasitic infections and cancer, were alterations of the host's immune responses are usually found, and therapy-induced modulation of the immune response is likely to be required.

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