Association of lesion area measured by colposcopy and cervical neoplasia.

Studies have demonstrated that the size of lesion in colposcopic imaging can be associated with the grade of CIN. We evaluated 36 patients and at the time of colposcopy, the images were recorded and analysed for lesion area measurement. A ROC curve was used to obtain the area under the curve and to determine the best cut-off values between area lesion (pixels2) and biopsy result. Fisher's exact test was performed (p < .05). Half of the sample had a cervical biopsy showing HPV or LSIL, and 18 (50%)a biopsy showing HSIL or invasive cancer. HSIL and invasive cancer were associated with a lesion area greater than 30,337.03 pixels2 (cut off) with p = .04. Thus the area of the colposcopic lesion is related to the severity of that; so small lesions can be more conservatively followed.IMPACT STATEMENT:What is already known on this subject? Studies have proposed that the size of lesion in colposcopic imaging can be associated with the grade of CIN, and the size of CIN lesions may be a factor in determining the risk of progression.What do the results of this study add? This is the first study in the literature that uses the measurement of the lesion area in pixels2 in comparison with the severity of the lesion, which provides greater accuracy of the lesion area than the mere measurement of its diameter.What are the implications of these findings for clinical practice and/or further research? The size of the lesion should be considered in the management of cervical intraepithelial lesions. This approach also leads to lower cost and is less invasive. Small lesions will have the best prognosis and would be treated in the way more conservative, bringing to the patients more comfort and less complications with the treatment.

Local profile of cytokines and nitric oxide in patients with bacterial vaginosis and cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the local immune response in patients with bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN), as assessed by cytokine and nitric oxide (NO) concentrations. STUDY DESIGN: Patients attending for routine gynaecological examination were prospectively enrolled in groups: BV (n=25) diagnosed by clinical criteria, CIN graded I to III (n=35, 6 CIN I, 8 CIN II and 21 CIN III) by histological analysis, and controls (n=15) without clinical and cytological findings. Randomly selected patients within CIN group at grades II or III (n=15) were re-evaluated at 60 days after surgical treatment. Endocervical (EC) and vaginal secretion samples were collected by cytobrush and the levels of cytokines (ELISA) and NO metabolite (Griess reaction) were assayed. RESULTS: NO was assessed in all subjects, and cytokines in all controls, 15 BV and 30 CIN patients. Interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and nitrite levels were higher in EC than in vaginal secretions in BV and CIN groups. In CIN group, IL-8, IL-10 and nitrite concentrations were greater in EC and/or vaginal secretions than in BV or controls. Surgical treatment reduced IL-8 levels in EC and vaginal secretions. CONCLUSION: A similar local immune profile was found in BV and CIN groups. The increased local production of IL-8, IL-10 and NO in CIN suggests a role for these mediators in the immune response against tumour or tumour development.

Failure of neutrophil chemotactic function in breast cancer patients treated with chemotherapy.

Neutrophil migration is a key host event against infection. Chemotherapy may alter neutrophil function and favor increased risk of infection. Herein, we investigated the effect of chemotherapy on the migration capacity of circulating neutrophils obtained from breast cancer patients and mechanisms involved in this event. Breast cancer women (n=23) at disease stage I-III and healthy control women (n=25) were prospectively enrolled. No differences in the in vitro migratory responses towards the chemotactic stimuli N-formyl- L-methionyl- L-leucyl- L-phenylalanine (fMLP), leukotriene B(4) (LTB(4)) and interleukin (IL)-8 were observed in purified neutrophils from controls and patients, in a microchemotaxis chamber assay. However, the migration capacity evaluated upon chemotherapy (5-fluoruracil, adriamycin and cyclophosphamide, 21-day intervals between cycles, total leukocyte count >/=2,000/mm(3)), on the day immediately before the beginning of the sixth cycle, showed that patient neutrophils (n=14) failed to migrate in response to fMLP compared to response observed upon diagnosis. Considering patients (n=8) with documented bacterial infection between cycles, the number of migrated neutrophils (mean+/-SD) compared to response at diagnosis was markedly reduced upon chemotherapy to either fMLP (30.1+/-8.26 vs. 2.81+/-1.28) or LTB(4) (15.72+/-4.8 vs. 2.8+/-1.64) stimuli respectively. Treatment of control neutrophils with sera of chemotherapy-treated patients with infective episodes, to test for the presence of circulating immunosuppressive factors, significantly reduced the migratory capacity of healthy neutrophils to fMLP, LTB(4) and IL-8, in a dose-dependent way. But no significant differences were found in the serum levels of nitric oxide (NO) metabolites, tumor necrosis factor (TNF)-alpha, IL-6, IL-8 and IL-10 collected at the same time as the collection of blood for neutrophil migration experiments. In conclusion, breast cancer patients showed suppressed neutrophil migratory response upon chemotherapy, accompanied by bacterial infection episodes. Circulating factors are involved, at least partially, in the inhibitory mechanism on neutrophil migration.

Mechanisms affecting neutrophil migration capacity in breast cancer patients before and after chemotherapy.

PURPOSE: To investigate the mechanisms affecting neutrophil migration capacity in breast cancer patients before and after chemotherapy. METHODS: Peripheral venous blood was collected at the time of diagnosis and immediately prior to the 4th cycle of an anthracycline-based chemotherapy regimen for patients diagnosed with different stages of breast cancer (n = 30), for experimental assays. Blood samples were also collected from a healthy control group (n = 17). RESULTS: IL-8 serum concentrations were higher in the patient group than in the control group (p = 0.02), and chemotherapy did not further affect this increase. Levels of TNF-α, IL-6, and IL-10 did not differ between controls and patients, or in relation to chemotherapy. Serum levels of nitric oxide (NO) metabolites were elevated following chemotherapy compared to levels detected prior to treatment (p = 0.01). When the supernatants of lipopolysaccharide-stimulated mononuclear cells and neutrophils obtained from the patients were assayed for levels of nitrite, these levels were significantly higher and unchanged, respectively, compared with controls. Expression levels of the chemokine receptors, CXCR1 and CXCR2, were significantly reduced in patients compared to controls, and chemotherapy did not further affect these differences. Furthermore, filamentous actin content for IL-8-activated neutrophils was reduced with chemotherapy (median 8.85; range 3.38-13.43) compared to the content detected prior to treatment (median 9.23; range 2.86-22.16) (p = 0.001). CONCLUSION: Elevated systemic levels of IL-8 and NO, desensitization to CXCR activation, and reduction in actin polymerization may affect neutrophil motility in patients before and after chemotherapy.

Rheumatoid arthritis-increased gene expressions in muscle atrophy are restored back to control as a response to acute resistance exercise / Estímulo agudo de musculação promove regulação de genes alterados pela atrofi a muscular

This study had as objective to analyze the acute eff ects of resistance exercise (RE) on the mRNA levels of the following genes (MyoD, myogenin, IGF-1, atrogin-1, MuRF-1, and myostatin) in rheumatoid arthritis (experimental arthritis). Therefore, 26 females rats were randomly allocated into four groups, control (CT, n=7), exercise (Ex, n=6), rheumatoid arthritis (RA, n=6) and RA with exercise (RAEx, n=7). Met-BSA was injected into the tibiotarsal joint in the RA and RAEx groups. After 15 days from injection, the animals were submitted to an acute bout of RE and six hours post protocol the animals were euthanized. We evaluated the joint thickness, infl ammation score, cross-sectional area (CSA) of gastrocnemius muscle fi bers and mRNA expression of the IGF-1, MyoD, myogenin, myostatin, MuRF-1, atrogin-1 and GAPDH. It was observed that the joint thickness and score strongly increased in arthritic rats (p <0.001) while the CSA decreased (p ≤ 0.05). Increased mRNA levels of IGF-1 (2.0 fold), myostatin (4.5 fold), atrogin-1 (2.5 fold), MyoD (3.7-fold) and myogenin (5 fold) were observed in muscle of arthritic rats. The mRNA expression of myostatin, atrogin-1, MyoD and myogenin decreased in the RAEx group. In this way, we can conclude that experimental arthritis-increased gene expressions in muscle atrophy myostatin, atrogin-1, MyoD and myogenin) are restored back to control as a response to acute RE....(AU)

O presente estudo teve como objetivo analisar o efeito agudo do Exercício com pesos sobre os níves de mRNA de genes envolvidos no anabolismo ou catabolismo muscular em um modelo experimental de Artrite Reumatóide. Para tanto, 26 ratas fêmeas foram randomicamente alocadas em quatro grupos, controle (CT, n=7), Exercício (Ex, n=6), Artrite Reumatóide (AR, n=6) e Artrite Reumatóide com exercício (AREx, n=7). Uma substância contendo Albumina bovina metilada foi injetada na articulação tíbio-tarsal nos grupos AR e AREx para indução da Artrite Reumatóide. Após 15 dias da injeção, os animais foram submetidos a um estímulo agudo de treinamento com pesos e 6 horas após o exercício os animais foram eutanasiados. Nós avaliamos a espessura da articulação, escore de infl amação, a área de secção transversa (AST) das fi bras do músculo Gastrocnêmio e a mRNA de IGF-1, MyoD, Myogenina (genes envolvidos no anabolismo muscular), e MuRF-1, atrogina-1 (genes envolvidos no catabolismo muscular), além do gene controle , GAPDH. Foi observado que a espessura articular e o escore de infl amação aumentaram fortemente nas ratas induzidas a Artrite Reumatóide (p <0,001), enquanto a AST reduziu (p ≤ 0,05). Um aumento nos níveis de mRNA de IGF-1 (2,0 vezes), miostatina (4,5 vezes), atrogina-1 (2,5 vezes), MyoD (3,7 vezes) e miogenina (5 vezes) foi observado no músculo das ratas induzidas a Artrite Reumatóide. mRNA de miostatina, atrogina-1, MyoD e miogenina reduziu no grupo RAEx. Desta forma, podemos concluir, que o modelo experimental de Artrite Reumatóide induziu um aumento da expressão de genes durante a atrofi a muscular (myostatin, atrogin-1, MyoD and myogenin) e que estas alterações foram reguladas pelo Exercício com peso....(AU)

Failure of neutrophil chemotactic function in septic patients.

OBJECTIVE: To investigate the in vitro chemotactic function of neutrophils obtained from patients with sepsis. DESIGN: Prospective study in which purified neutrophils obtained from septic patients and nonseptic control volunteers were assayed for chemotactic function induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and leukotriene B4. The sera nitrate concentrations also were quantified. SETTING: University hospital. PATIENTS: Twenty patients with sepsis caused by different infectious foci. INTERVENTIONS: Routine blood tests, blood or other site cultures, blood collection for neutrophil purification sera collection for nitrate assay. MEASUREMENTS AND MAIN RESULTS: Neutrophils from septic patients exhibited significantly less chemotactic activity than neutrophils obtained from healthy volunteers, in response to FMLP (93.4 +/- 6.6 vs. 51 +/- 8.3 migrated neutrophils) and leukotriene B4 (90.2 +/- 10 vs. 42.4 +/- 11.6 migrated neutrophils) stimuli, in a microchemotaxis chamber assay. The impaired chemotaxis occurred mainly in neutrophils from nonsurvivor patients. The extent of neutrophil chemotaxis inhibition (survivor/nonsurvivor) was 33.43%/61.67% and 43.4%/86.98%, in response to FMLP and leukotriene B4, respectively. Increased serum nitrate (micromoles of NO2 + NO3) concentrations were detected in septic patients, compared with controls, but no differences were found between survivor (91.84 +/- 14.12) and nonsurvivor (102.6 +/- 17.36) groups. CONCLUSIONS: Septic patients present suppressed neutrophil chemotactic responses to FMLP and leukotriene B4 stimuli compared with healthy controls. This is accompanied by increased serum concentrations of nitrate. The impairment of neutrophil chemotaxis was observed mainly in the cells obtained from nonsurvivor patients and may thus be an additional factor contributing to disease outcome.

Pseudopuberdade precoce causada por tumor de células da granulosa juvenil / Psedo-precocious puberty due to a juvenile granulosa cell tumor

Descrevemos um caso de tumor ovariano das células da granulosa cuja manifestaçäo inicial foi puberdade precoce isossexual, em criança de 7 anos e 4 meses, de evoluçäo progressiva e rápida, associada a massa hipogástrica palpável. A avaliaçäo hormonal demonstrou estradiol: 296pg/ml; 17aOH-progesterona: 20ng/ml; S-DHEA: 27µg/dl; PhCG: 0,66mU1/ml; testosterona: 120ng/dl; progesterona: 3,4ng/ml; LH: 0,5mUl/ml; e FSH: 0,01 mUl/ml e näo responsivos ao estímulo com o GnRH, (Relisorm: 100µg iv). Exames de imagem confirmaram massa tumoral em ovário esquerdo. A paciente foi submetida à salpingo-ooforectomia esquerda com retirada completa do tumor que pesou 656g e mediu 14,5 x 10,0 x 7,Ocm, restrito ao ovário e cujo exame histopatológico demonstrou tumor de cérúlas da granulosa juvenil. Durante a cirurgia amostras sangüíneas foram obtidas da veia ovariana ipsilateral ao tumor e as concentraçöes de esteróides foram estudadas. Níveis elevados de estradiol (969pg/ml), progesterona (15,8ng/ml), 17aOH-progesterona (34ng/ml) e testosterona (158ng/dl) foram encontrados. No pós-operatório observou-se rápida regressäo das mamas, dos pêlos pubianos, com normalizaçäo das concentraçöes hormonais. Durante o seguimento, a paciente apresentou desenvolvimento puberal normal, e näo há sinais de reincidência do tumor.

Tumor filóide maligno: relato de casos e atualização / Malignant phyllodes tumor: relate of cases and updating

O tumor filóide representa menos de 1% de todos os tumores de mama. Cerca de 30% apresentam comportamento maligno. É um tumor fibroepitelial semelhante ao fibroadenoma. São apresentados dois casos de tumor filóide maligno. O tratamento foi cirúrgico, já que são rádio e quimiorresistentes. Ambos os casos apresentam recorrência e novamente foram operados. É feita uma atualização da literatura.

Phyllodes tumour represents less than 1% of all breast tumours. About 30% will exhibit malignant behaviour. It's similar to a fibroadenoma. We report two cases of malignant phyllodes tumours. The treatment of choice was surgical once they are both resistant to radiotherapy and chemotherapy. The two cases showed recurrence and were operated again. An updating of the literature is done.