RESUMO
PURPOSE: Incisional hernia (IH) has an incidence of 10-23%, which can increase to 38% in specific risk groups. The objective of this study is to report the results at 3 years of follow-up of the use of the reinforced tension line (RTL) technique compared with primary suture only (PSO) closure in the prevention of IH in high-risk patients undergoing laparotomy. METHODS: Open randomized controlled clinical trial. Included were patients older than 18 years who underwent midline laparotomy, emergency or scheduled, who were considered high risk, and who completed 3-year follow-up. The patients were randomized 1:1 to the RTL technique or to PSO. The objective was to report the incidence of IH and the complications associated with the closure method. Intention-to-treat analysis and Cox regression were performed. RESULTS: A total of 124 patients were randomized; 51 patients from the RTL group and 53 patients from the PSO group finished the 3-year follow-up. The incidence of IH was higher in the PSO group (15/53, 28.3%) than the RTL group (5/51, 9.8%) (p = 0.016, OR 0.35, 95% CI 0.14-0.88, number needed to treat 5.4, log-rank test p = 0.017). The groups were similar in the rates of surgical site infection, hematoma, seroma, and postoperative pain during follow-up. CONCLUSIONS: The RTL technique is useful in the prevention of IH when compared with PSO in high-risk midline laparotomy patients, and it is not associated with a higher percentage of complications. TRIAL REGISTRATION: Local Committee CI-HRAEB-2013-020. March 13, 2013. CLINICAL TRIALS: NCT02136628, retrospectively registered.
Assuntos
Técnicas de Fechamento de Ferimentos Abdominais , Hérnia Incisional , Técnicas de Fechamento de Ferimentos Abdominais/efeitos adversos , Seguimentos , Herniorrafia/efeitos adversos , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Laparotomia/efeitos adversos , Laparotomia/métodos , Técnicas de Sutura/efeitos adversos , Suturas/efeitos adversosRESUMO
AIM: To establish the utility of baseline 18F-Fluorocholine (FCH) PET/CT and bone scintigraphy (BS) in the outcome prediction of patients with castration-resistant prostate cancer and bone metastases (CRPC-BM) treated with 223Ra. METHODS: Prospective, multicenter and non-randomized study (ChoPET-Rad study). FCH PET/CT and BS were performed before the initiation of 223Ra (basal FCH PET/CT and BS). Bone disease was classified attending the number of lesions in baseline BS and PET/CT. FCH PET/CT was semiquantitatively evaluated. Gleason score, baseline levels of prostate-specific antigen (PSA), alkaline phosphatase and lactate dehydrogenase were determined. Progression-free survival (PFS) and overall survival (OS) since the onset of 223Ra treatment was calculated. PFS was defined by PSA rising. Relations between clinical and imaging variables with PFS and OS were evaluated by Pearson, Mann-Whitney tests and Kapplan-Meier analysis. Univariate and multivariate Cox regression analysis was performed. RESULTS: Forty patients were evaluated. The median PFS and OS were of 3.0 ± 2.3 and 23.0 ± 4.2 months, respectively. 33 patients progressed and 13 died during the follow-up. The extension of the bone disease by FCH PET/CT (p = 0.011, χ2 = 10.63), BS (p = 0.044, χ2 = 8.04), SUVmax (p = 0.012) and average SUVmax (p = 0.014) were related to OS. No significant association was found for the PFS. ROC analysis revealed significant association of SUVmax, average SUVmax and basal PSA with OS. Only therapeutic failure was associated with OS in the multivariate analysis (HR = 3.6, p = 0.04). CONCLUSION: FCH PET/CT and BS had prognostic aim in the prediction of OS. None clinical or imaging variable was able to predict the PFS, probably due to the high rate of progressive disease.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/radioterapia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Colina/análogos & derivados , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Neoplasias de Próstata Resistentes à Castração/secundário , Radioisótopos/uso terapêutico , CintilografiaRESUMO
The 17ß-hydroxysteroid dehydrogenases (17ß-HSD) are key enzymes involved in the formation (reduction) and inactivation (oxidation) of sex steroids. Several types have been found in vertebrates including fish, as well as in invertebrates like Caenorhabditis elegans, Ciona intestinalis and Haliotis diversicolor supertexta. To date limited information is available about this enzyme in parasites. We showed previously that Taenia solium cysticerci are able to synthesize sex steroid hormones in vitro when precursors are provided in the culture medium. Here, we identified a T. solium 17ß-HSD through in silico blast searches in the T. solium genome database. This coding sequence was amplified by RT-PCR and cloned into the pcDNA 3.1(+) expression vector. The full length cDNA contains 957bp, corresponding to an open reading frame coding for 319 aa. The highest identity (84%) at the protein level was found with the Echinococcus multilocularis 17ß-HSD although significant similarities were also found with other invertebrate and vertebrate 17ß-HSD sequences. The T. solium Tsol-17ßHSD belongs to the short-chain dehydrogenase/reductase (SDR) protein superfamily. HEK293T cells transiently transfected with Tsol17ß-HSD induced expression of Tsol17ß-HSD that transformed 3H-androstenedione into testosterone. In contrast, 3H-estrone was not significantly transformed into estradiol. In conclusion, T. solium cysticerci express a 17ß-HSD that catalyzes the androgen reduction. The enzyme belongs to the short chain dehydrogenases/reductase family and shares motifs and activity with the type 3 enzyme of some other species.
Assuntos
17-Hidroxiesteroide Desidrogenases/genética , 17-Hidroxiesteroide Desidrogenases/metabolismo , Hormônios Esteroides Gonadais/biossíntese , Taenia solium/enzimologia , Taenia solium/genética , Sequência de Aminoácidos , Androstenodiona/biossíntese , Animais , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica , Células HEK293 , Humanos , Dados de Sequência Molecular , Filogenia , Testosterona/biossínteseRESUMO
Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P4) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence of HPV was studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P4. KCNH1 mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types of HPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P4 induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P4 was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P4 in human cells. These data raise a new research field for KCNH1 channels in human tissues.
Assuntos
Colo do Útero/metabolismo , Canais de Potássio Éter-A-Go-Go/genética , Gravidez/genética , Progesterona/farmacologia , Adolescente , Adulto , Colo do Útero/efeitos dos fármacos , Colo do Útero/patologia , Canais de Potássio Éter-A-Go-Go/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Papillomaviridae/isolamento & purificação , Gravidez/metabolismo , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/genética , Complicações Infecciosas na Gravidez/metabolismo , Receptores de Progesterona/genética , Esfregaço Vaginal , Adulto JovemRESUMO
Taenia solium and Taenia crassiceps WFU cysticerci and tapeworms have the ability to synthesize sex steroid hormones and have a functional 3ß-hydroxisteroid dehydrogenase. Corticosteroids (CS) like corticosterone and dexamethasone have been shown to stimulate in vitro estrogen production by Taenia crassiceps WFU cysticerci. The aim of this work was to study the ability of T. crassiceps WFU cysticerci to synthesize corticosteroids, and the effect of the inhibitor metyrapone on the CS synthesis. For this purpose T. crassiceps WFU cysticerci were obtained from the abdominal cavity of mice, thoroughly washed and pre-incubated in multiwells for 24 h in DMEM plus antibiotics/antimycotics. The tritiated CS precursor progesterone ((3)H-P4) was added to the culture media and parasites cultured for different periods. Blanks containing the culture media plus the (3)H-P4 were simultaneously incubated. Blanks and parasite culture media were ether extracted and analyzed by thin layer chromatography (TLC) in two different solvent systems. Corticosterone production was measured in the culture media by RIA. In some experiments metyrapone (0.1-0.5 mM) was added for 24, 48 or 72 h. Results showed that cysticerci mainly synthesized tritiated 11-deoxy corticosterone (DOC) and small amounts of corticosterone that was also detected by RIA. Small amounts of (3)H-11-deoxy cortisol were also found. Corticosteroid synthesis was time dependent. The addition of metyrapone significantly inhibited tritiated DOC, deoxycortisol and corticosterone synthesis. These results show for the first time that parasites have the capacity to synthesize CS that is modulated by metyrapone. Data suggest that DOC is the main corticosteroid in the parasites.
Assuntos
Antimetabólitos/farmacologia , Desoxicorticosterona/metabolismo , Metirapona/farmacologia , Progesterona/metabolismo , Taenia/metabolismo , Animais , Cromatografia em Camada Fina , Desoxicorticosterona/análise , RadioimunoensaioRESUMO
Penalized likelihood analysis of previously published chloroplast DNA (cpDNA) ndhF sequences suggests that the central-southern Andean genus Chaetanthera diverged ca. 16.5 million years (my) ago, well before the uplift of the Andes to their present heights. Penalized likelihood analysis based on new nuclear ribosomal DNA (rDNA) internal transcribed spacer (ITS) sequences indicates that the most relictual lineages occupy high elevation Andean habitats that did not exist until some 10my later. This result is contrary to the expectation that younger habitats should be occupied by phylogenetically younger lineages. The results are interpreted with respect to the development of aridity in lowland habitats during the Miocene and Pliocene, which presumably extinguished the lowland relatives of the high elevation taxa or, in effect, forced them upwards in search of adequate moisture. As the more northerly lineages were being displaced upward, others diversified in the mediterranean-type climate area of central Chile, giving rise to additional high elevation taxa again, at an early date, as well as lowland taxa. Some species of Chaetanthera from lowland central Chile appear as the phylogenetically youngest taxa, suggesting secondary adaptation to lowland aridity. At the same time, at least two high elevation species, Chaetanthera peruviana and Chaetanthera perpusilla, appear to have been derived recently from a lower elevation ancestor, while some middle to low elevation taxa seem to have evolved recently out of a high elevation complex. The results suggest that the younger high elevation habitats have served as both "cradle" and "museum" for Chaetanthera lineages.
Assuntos
Asteraceae/genética , DNA Espaçador Ribossômico/genética , Evolução Molecular , NADH Desidrogenase/genética , Filogenia , Proteínas de Plantas/genética , Asteraceae/classificação , Variação Genética , Dados de Sequência Molecular , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
The objective of this study was to assess the relationship between the bone strontium content and bone histomorphometric parameters in bone biopsies from patients with chronic renal failure undergoing hemodialysis. The study was carried out in 74 illiac crest bone biopsies from patients with renal osteodystrophy from different worldwide regions (Argentina, Portugal and Spain). They were underwent to histological and histomorphometric evaluation. The bone strontium/calcium ratio was measured by quadrupole inductively coupled plasma-mass spectrometry. The samples were classified into groups according to histological criteria: hyperparathyroidism (HP), mixed (MX), osteomalacia (OM) and adynamic bone disease (ABD). Serum PTH and alkaline phosphatase before biopsy were available in most of the patients. No correlation was found between the different histomorphometric parameters and the Sr/Ca ratio. The one way ANOVA test showed statistical differences in the Sr/Ca ratio of the different histological forms (HP: 0.58 +/- 0.39; MX: 1.16 +/- 0.74; OM: 1.10 +/- 0.46; ABD: 0.91 +/- 0.40 microgram Sr/mg Ca; p < 0.003). The post-Hoc analysis showed differences between HP and MX. The biopsies having greater or equal values than 1.4 micrograms Sr/mg Ca showed higher levels of bone formation histomorphometric parameters and serum alkaline phosphatase (395 +/- 519 vs 1,022 +/- 989 UI/L, p < 0.05). Although it has been found that the biopsies with higher bone strontium had higher levels of osteoid tissue (characteristic of osteomalacia), the hypothesis of strontium-induced osteomalacia could not be demonstrated.
Assuntos
Osso e Ossos/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Soluções para Hemodiálise/efeitos adversos , Falência Renal Crônica/metabolismo , Osteomalacia/induzido quimicamente , Diálise Renal , Estrôncio/efeitos adversos , Fosfatase Alcalina/sangue , Argentina/epidemiologia , Biópsia , Osso e Ossos/química , Cálcio/análise , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Soluções para Hemodiálise/química , Humanos , Hiperparatireoidismo Secundário/etiologia , Ílio/química , Ílio/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Osteomalacia/epidemiologia , Osteomalacia/etiologia , Hormônio Paratireóideo/sangue , Portugal/epidemiologia , Diálise Renal/efeitos adversos , Espanha/epidemiologia , Estrôncio/análiseRESUMO
BACKGROUND: Cisplatin-based chemoradiation for locally advanced cervical carcinoma is now the standard of care for most patients with cervical carcinoma. However, induction chemotherapy followed by surgery, particularly with newer agents or combinations remains to be explored. This study was undertaken to evaluate the antitumor activity and toxicity of gemcitabine in combination with cisplatin for untreated locally advanced cervical carcinoma. PATIENTS AND METHODS: Open-label, single center, phase II, non-randomized study of neoadjuvant gemcitabine plus cisplatin. Forty-one patients with histologic diagnosis of cervical carcinoma, with no previous treatment and staged as IB2 to IIIB, were treated with three 21-day courses of cisplatin 100 mg/m2 day I and gemcitabine 1000 mg/m2 days 1 and 8, followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated before each course and at the end of chemotherapy. RESULTS: All patients were evaluated for toxicity and 40 for response. The overall objective response rate was 95% (95% confidence interval (CI): 88%-100%) being complete in 3 patients (7.5%) and partial in 35 (87.5%). A complete pathological response was found in 6 (26%) of the 23 patients that underwent surgery. Granulocytopenia grades 3-4 occurred in 13.8% and 3.4% of the courses, respectively, whereas non-hematological toxicity was mild. CONCLUSIONS: Induction chemotherapy with the combination of gemcitabine and cisplatin is highly active for untreated cervical cancer patients and has an acceptable toxicity profile.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , GencitabinaRESUMO
The effects of thymectomy performed on 10-day-old (Tx-10) mice on spontaneous puberty and the ovulatory response induced by gonadotrophin treatment were analysed, together with the effects of thymulin replacement from 10 days of age. Infantile thymectomy induced a delay of puberty, a decrease in serum 17beta-oestradiol concentration and a reduced total number of follicles. Injection of thymulin (12 ng/g body weight) to Tx-10 mice resulted in an earlier onset of puberty, a decrease in the weights of ovaries and uterus, and an increase in serum 17beta-oestradiol concentrations. In control and Tx-10 mice, treatment with pregnant mare serum gonadotrophin (PMSG) (5 IU) at 25 days of age resulted in ovulation and the numbers of ova shed by ovulating animals were similar. When the animals were injected with 1 IU PMSG ovulation did not occur. In Tx-10 mice, both 1 and 5 IU PMSG increased the number of follicles to values similar to those observed in the controls. In Tx-10 mice the sequential injection of PMSG (1 IU) and human chorionic gonadotrophin (hCG) (3 IU) resulted in ovulation, but the number of ova shed was lower than in controls. When these animals were injected daily with thymulin, an increase in the number of ova shed and serum 17beta-oestradiol concentrations was observed. The uterine weight of Tx-10 mice was always significantly reduced in response to gonadotrophin treatment. Thymulin injection in PMSG-hCG-treated Tx-10 mice provoked a significant increase in uterine weight. The results suggest that the presence of the thymus after the neonatal period is necessary to normal ovarian development and function. The increase in gonadotrophin-induced ovarian response produced by thymulin replacement indicates that this peptide has a role in this process as one of the connecting signals between thymus and ovaries.