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1.
Langmuir ; 34(29): 8652-8660, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29957953

RESUMO

Here, the morphology of polypore fungi has inspired the fabrication of poly(vinylidene fluoride) (PVDF) membranes with dual porosity by nonsolvent-induced phase separation (NIPS). The fruiting body of such microorganisms is constituted of two distinct regions, finger- and sponge-like structures, which have been successfully mimicked by controlling the coagulation bath temperature during the NIPS process. The use of water at 10 °C as coagulant resulted in membranes with the highest finger-like/sponge-like ratio (53% of the total membrane thickness), while water at 90 °C allowed the formation of macrovoid-free membranes. The microchannels and the asymmetric porosity were used to enhance the oil sorption capacity of the PVDF membranes and to achieve directional release of therapeutic essential oils. These PVDF membranes with easily tuned asymmetric channel-like porosity and controlled pore size are ideal candidates for drug delivery applications.


Assuntos
Sistemas de Liberação de Medicamentos , Óleos Voláteis/química , Polivinil/química , Membranas Artificiais , Óleos Voláteis/administração & dosagem , Porosidade
2.
J Pediatr Urol ; 14(6): 538.e1-538.e7, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29885870

RESUMO

BACKGROUND: It is extremely important to not only address the short-term success following endoscopic correction of vesicoureteral reflux (VUR) but also the long-term efficacy and safety of the tissue augmenting substance utilized for endoscopic correction. OBJECTIVE: This study retrospectively evaluated all cases of ureterovesical junction (UVJ) obstruction following endoscopic treatment of VUR over the last 5 years utilizing two tissue augmenting substances, with special emphasis on the safety of Vantris®, and performed clinical and histological review of these patients. METHODS: The study population comprised 2495 patients who underwent endoscopic correction of VUR utilizing Deflux® (1790) and Vantris® (705). Tissue sections were stained with hematoxylin & eosin and trichrome, and examined under a light microscope. Nine primary obstructive megaureters after ureteral re-implantation served as controls. RESULTS: Nine (0.5%) children (three female and six male) in the Deflux group and nine (1.3%) (five females and four males) in the Vantris group developed UVJ obstruction and required ureteral re-implantation. Obstruction developed during the period ranging 2-49 months (average 16 months) following endoscopic correction. The primary reflux grade was III in seven, IV in six, and V in six children. The mean volume of the injected material in all obstructed patients was 1.2 ± 0.6 cc (mean ± SD). Histopathological analysis revealed a pseudocapsule composed of fibrous tissue and foreign-body giant cells surrounding the Vantris implant in all patients. The distal part of the ureters demonstrated significant ureteral dilatation without ureteral fibrosis. In all patients, additional biopsies from the muscularis propria adjacent to the injection site were examined and showed no significant abnormalities. There was an increased collagen deposition in the juxtavesical segment of the obstructive ureters following Deflux and Vantris injections, and of primary obstructive megaureter. No significant difference was found in the tissue response between Deflux and Vantris patients and controls. Statistical analysis of the nonhomogeneous population demonstrated higher obstruction rates in patients from the Vantris group. However, no statistical difference was demonstrated regarding the obstruction rate in the homogenous group with relation to gender, age and reflux grade group of patients. Moreover, univariate analysis revealed that Grade V reflux, the presence of beak sign on the reviewed pretreatment, and inflamed bladder mucosa upon injection were significant independent risk factors leading to obstruction. DISCUSSION: This study suggested that the underlining ureteral pathology lead to UVJ obstruction following Vantris injection. There was increased collagen deposition in the juxtavesical segment of the obstructive ureters following Vantris injection. Furthermore, these findings were similar to those discovered in patients who underwent endoscopic correction with Deflux, and in patients who required ureteral reimplantation due to primary obstructive megaureter. Additional biopsies from the muscularis propria adjacent to the injection site showed no significant abnormalities, ironing out the fact that Vantris did not led to adverse tissue reaction following injection. Univariate analysis further ironed out the hypothesis that underlying ureteral pathology was responsible for the increased incidence of UVJ obstruction and demonstrated that Grade V reflux, the presence of beak sign on the reviewed pretreatment VCUG, and inflamed bladder mucosa upon injection were significant independent risk factors leading to obstruction. CONCLUSION: Data showed that Vantris injection did not lead to any different ureteral fibrosis or inflammatory changes to the tissue augmenting substances utilized in past and present clinical practice, and therefore did not seem to increase the incidence of UVJ obstruction. High reflux grade, presence of obstructive/refluxing megaureter and inflamed bladder mucosa were the only statistically significant and independent predictive factors for UVJ obstruction following endoscopic correction of VUR.


Assuntos
Resinas Acrílicas/administração & dosagem , Cistoscopia , Dextranos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Pelve Renal , Obstrução Ureteral/epidemiologia , Ureteroscopia , Refluxo Vesicoureteral/terapia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Injeções Intralesionais , Masculino , Estudos Retrospectivos , Obstrução Ureteral/etiologia
3.
J Mater Chem B ; 6(6): 930-939, 2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32254373

RESUMO

Properly engineered scaffolds combined with functional neurons can be instrumental for the effective repair of the neural tissue. In particular, it is essential to investigate how three-dimensional (3D) systems and topographical features can impact on neuronal activity to obtain engineered functional neural tissues. In this study, polyphenylene sulfone (PPSu) scaffolds constituted by randomly distributed or aligned electrospun nanofibers were fabricated to evaluate the neural activity in 3D culture environments for the first time. The obtained results demonstrated that the nanofibers can successfully support the adhesion and growth of neural stem cells (NSCs) and enhance neuronal differentiation compared to 2D substrates. In addition, NSCs could spread and migrate along the aligned fibers. The percentage of active NSC-derived neurons and the overall network activity in the fibrous substrates were also remarkably enhanced. Finally, the data of neuronal activity showed not only that the neurons cultured on the nanofibers are part of a functional network, but also that their activity increases, and the direction of neural signals can be controlled in the aligned 3D scaffolds.

4.
Biomed Mater ; 11(4): 041001, 2016 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-27481333

RESUMO

In the biomedical sector the availability of engineered scaffolds and dressings that control and reduce inflammatory states is highly desired, particularly for the management of burn wounds. In this work, we demonstrate for the first time, to the best of our knowledge, that electrospun fibrous dressings of poly(octyl cyanoacrylate) (POCA) combined with polypropylene fumarate (PPF) possess anti-inflammatory activity and promote the fast and effective healing of mild skin burns in an animal model. The fibers produced had an average diameter of (0.8 ± 0.1) µm and they were able to provide a conformal coverage of the injured tissue. The application of the fibrous mats on the burned tissue effectively reduced around 80% of the levels of pro-inflammatory cytokines in the first 48 h in comparison with un-treated animals, and enhanced skin epithelialization. From histological analysis, the skin thickness of the animals treated with POCA : PPF dressings appeared similar to that of one of the naïve animals: (13.7 ± 1.4) µm and (14.3 ± 2.5) µm for naïve and treated animals, respectively. The density of dermal cells was comparable as well: (1100 ± 112) cells mm(-2) and (1358 ± 255) cells mm(-2) for naïve and treated mice, respectively. The results demonstrate the suitability of the electrospun dressings in accelerating and effectively promoting the burn healing process.


Assuntos
Anti-Inflamatórios/farmacologia , Queimaduras/terapia , Modelos Animais de Doenças , Fumaratos/farmacologia , Nanofibras/química , Polipropilenos/farmacologia , Dermatopatias/terapia , Cicatrização/efeitos dos fármacos , Animais , Bandagens , Queimaduras/etiologia , Queimaduras/patologia , Cianoacrilatos/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dermatopatias/etiologia , Dermatopatias/patologia , Raios Ultravioleta/efeitos adversos
5.
J Urol ; 196(3): 875-80, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27154824

RESUMO

PURPOSE: In pediatric renal transplant recipients there are some indications for native nephrectomy, which can be performed before, during or after transplantation. Indications include massive proteinuria resistant to therapy, intractable hypertension, polyuria and chronic or recurrent kidney infections. Several scientific studies of adults have demonstrated a minimally invasive alternative to native nephrectomy, which consists of ligation of the native ureter without removing the kidney. We evaluated the safety and efficacy of this minimally invasive technique in pediatric recipients of renal transplantation. MATERIALS AND METHODS: A total of 29 pediatric kidney transplant recipients underwent unilateral native ureteral ligation during renal transplantation between 2009 and 2013 (group A). In addition, a control group of 21 pediatric renal transplant recipients was enrolled who had undergone unilateral native nephrectomy between January 2005 and December 2008 (group B). Both groups were evaluated preoperatively by Doppler ultrasound of the native kidneys. RESULTS: Statistical analysis of the 2 groups for the 3 main variables considered (surgical time, intraoperative blood loss and length of surgical scar) revealed a significant difference (Mann-Whitney U test, p <0.001). This finding confirmed the hypothesis that during renal transplantation ligation of the native ureter is less invasive than native nephrectomy. CONCLUSIONS: Ligation of the native ureter without removal of the ipsilateral kidney is a feasible procedure in pediatric renal transplant recipients. This method is easy to perform and significantly less invasive than surgical nephrectomy.


Assuntos
Nefropatias/cirurgia , Transplante de Rim/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Nefrectomia/métodos , Doadores de Tecidos , Ureter/cirurgia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Ligadura , Masculino , Estudos Prospectivos , Transplantados , Transplante Homólogo , Resultado do Tratamento
6.
J Mater Chem B ; 4(28): 4801-4812, 2016 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32263137

RESUMO

In the last few years, the health-care services have registered worldwide an increased number of patients suffering from chronic wounds and ulcers, which are mainly associated with diabetes, obesity and cancer. The need for regenerating rapidly and effectively the injured skin has stimulated the research of advanced therapies for wound care. This review will discuss how biomimetic architectures produced by electrospinning natural biopolymers fulfil most of the requirements of ideal wound dressings. It will also examine the recent progress in the area of portable electrospinning systems and of multiscale instructive materials that integrate stimuli responsive and sensing elements.

7.
Hernia ; 18(3): 339-42, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23703291

RESUMO

PURPOSE: To report our experience using a modified orchidopexy with division and non-ligation of the processus vaginalis. METHODS: We performed a single-centre retrospective analysis of all patients who underwent orchidopexy between December 2005 and October 2008 at our institution. In the present technique, the processus vaginalis was gently peeled off the spermatic cord structures as high as possible and severed at the level of the internal inguinal ring without its ligation. Postoperative follow-up was routinely offered to all patients. Additionally, we made a special clinical follow-up, ranging from 1 to 69 months (median 34). RESULTS: One hundred and twenty-three patients, aged 1-11 years (median 3), underwent 147 orchidopexies during the study period. Of these, 25 were accomplished using conventional division and ligation of the processus vaginalis, and in the remaining 122 orchidopexies, the processus vaginalis was only divided. Of the 137 testes available at follow-up, 134 were in the scrotum and 3 (2 %) required re-do orchidopexy due to secondary reascent, including 2 treated with division only of the processus vaginalis. None of the patients experienced postoperative hydrocele or inguinal hernia development. CONCLUSIONS: Our findings confirm that division without ligation of a patent processus vaginalis is usually followed by spontaneous peritoneal scarring and complete closure of the internal inguinal ring. Present technique is as effective as traditional orchidopexy and saves extra time spent for meticulous closure of the processus vaginalis or peritoneal tears.


Assuntos
Criptorquidismo/cirurgia , Orquidopexia/métodos , Criança , Pré-Escolar , Hérnia Inguinal/etiologia , Humanos , Lactente , Ligadura , Masculino , Peritônio/cirurgia , Estudos Retrospectivos
8.
Int J Radiat Oncol Biol Phys ; 50(4): 1003-11, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11429228

RESUMO

PURPOSE: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. METHODS AND MATERIALS: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with (192)Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. RESULTS: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. CONCLUSION: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Radioisótopos de Irídio/uso terapêutico , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dosagem Radioterapêutica
9.
Curr Biol ; 11(8): 614-9, 2001 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-11369207

RESUMO

Ras p21 signaling is involved in multiple aspects of growth, differentiation, and stress response [1-2]. There is evidence pointing to superoxides as relays of Ras signaling messages. Chemicals with antioxidant activity suppress Ras-induced DNA synthesis. The inhibition of Ras significantly reduces the production of superoxides by the NADPH-oxidase complex [3]. Kirsten and Harvey are nonallelic Ras cellular genes that share a high degree of structural and functional homology. The sequences of Ki- and Ha-Ras proteins are almost identical. They diverge only in the 20-amino acid hypervariable domain at the COOH termini. To date, their functions remain indistinguishable [4]. We show that Ki- and Ha-Ras genes differently regulate the redox state of the cell. Ha-Ras-expressing cells produce high levels of reactive oxygen species (ROS) by inducing the NADPH-oxidase system. Ki-Ras, on the other hand, stimulates the scavenging of ROS by activating posttranscriptionally the mitochondrial antioxidant enzyme, Mn-superoxide dismutase (Mn-SOD), via an ERK1/2-dependent pathway. Glutamic acid substitution of the four lysine residues in the polybasic stretch at the COOH terminus of Ki-Ras completely abolishes the activation of Mn-SOD, although it does not inhibit ERK1/2-induced transcription. In contrast, an alanine substitution of the cysteine of the CAAX box has very little effect on Mn-SOD activity but eliminates ERK1/2- dependent transcription.


Assuntos
Genes ras/fisiologia , Transdução de Sinais/fisiologia , Células 3T3 , Animais , Células COS , Linhagem Celular , Chlorocebus aethiops , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Oxirredução , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
10.
J Am Coll Cardiol ; 37(1): 51-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11153772

RESUMO

OBJECTIVE: The purpose of this study was to compare percutaneous transluminal coronary revascularization (PTCR) employing stent implantation to conventional coronary artery bypass graft surgery (CABG) in symptomatic patients with multivessel coronary artery disease. BACKGROUND: Previous randomized studies comparing balloon angioplasty versus CABG have demonstrated equivalent safety results. However, CABG was associated with significantly fewer repeat revascularization procedures. METHODS: A total of 2,759 patients with coronary artery disease were screened at seven clinical sites, and 450 patients were randomly assigned to undergo either PTCR (225 patients) or CABG (225 patients). Only patients with multivessel disease and indication for revascularization were enrolled. RESULTS: Both groups had similar clinical demographics: unstable angina in 92%; 38% were older than 65 years, and 23% had a history of peripheral vascular disease. During the first 30 days, PTCR patients had lower major adverse events (death, myocardial infarction, repeat revascularization procedures and stroke) compared with CABG patients (3.6% vs. 12.3%, p = 0.002). Death occurred in 0.9% of PTCR patients versus 5.7% in CABG patients, p < 0.013, and Q myocardial infarction (MI) occurred in 0.9% PTCR versus 5.7% of CABG patients, p < 0.013. At follow-up (mean 18.5 +/- 6.4 months), survival was 96.9% in PTCR versus 92.5% in CABG, p < 0.017. Freedom from MI was also better in PTCR compared to CABG patients (97.7% vs. 93.4%, p < 0.017). Requirements for new revascularization procedures were higher in PTCR than in CABG patients (16.8% vs. 4.8%, p < 0.002). CONCLUSIONS: In this selected high-risk group of patients with multivessel disease, PTCR with stent implantation showed better survival and freedom from MI than did conventional surgery. Repeat revascularization procedures were higher in the PTCR group.


Assuntos
Angioplastia Coronária com Balão , Ponte de Artéria Coronária , Doença das Coronárias/terapia , Stents , Idoso , Argentina , Doença das Coronárias/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
11.
Prev Cardiol ; 4(2): 57-64, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11828201

RESUMO

The relationship between a history of hypertension and the quality of its control in routine clinical practice and the risk of acute myocardial infarction was examined in a multicenter, case-control study conducted in Argentina between November 1991 and August 1994, within the framework of the FRICAS study. The cases were 939 patients with acute myocardial infarction and without a history of ischemic heart disease. The controls were 949 subjects identified in the same centers as the cases and admitted with a wide spectrum of acute disorders unrelated to known or suspected risk factors for acute myocardial infarction. The odds ratios and the 95% confidence intervals were derived from multiple logistic regression equations, including terms for age, gender, education, social status, exercise, smoking status, cholesterolemia, history of diabetes, body mass index, and family history of myocardial infarction. The quality of hypertension control was assessed with the most recent blood pressure reading reported by the subjects. Seventy-two percent of hypertensive cases and 62.6% of hypertensive controls had a history of antihypertensive therapy by self-report, when admitted to the medical center. The adjusted odds ratio for acute myocardial infarction due to hypertension was 2.58 (95% confidence interval, 2.08-3.19). The odds ratio was 2.42 (95% confidence interval, 1.88-3.11) when hypertensives reported that their greatest systolic value was below 200 mm Hg (moderate status) and 4.12 (95% confidence interval, 2.87-5.89) when it was above 200 mm Hg (severe status). When the highest diastolic blood pressure value was below 120 mm Hg (moderate status), the risk increased to 2.48 (95% confidence intervals, 1.90-3.24) and to 4.12 (95% confidence interval, 2.83-5.99) when it was above 120 mm Hg (severe status). If the most recent systolic blood pressure was less-than-or-equal140 mm Hg, the odds ratio was 2.59 (95% confidence interval, 1.96-3.41), and it was 3.42 (95% confidence interval, 2.40-4.87) when the value was >140 mm Hg. If the most recent diastolic blood pressure was less-than-or-equal90 mm Hg, the risk increased more than two fold (odds ratio=2.48; 95% confidence interval, 1.91-3.22), and if it was >90 mm Hg, it increased nearly four-fold (odds ratio=3.72; 95% confidence interval, 2.33-5.96). In smokers, the odds ratio was 2.28 in the absence of hypertension and increased to 7.51 when hypertension was present. In this Argentine population, hypertension is a strong and independent risk factor for acute myocardial infarction. In routine clinical practice, the control of blood pressure to levels below 140/90 seems to be required in order to reduce part (but not all) of the risk of acute myocardial infarction in hypertensive patients. (c) 2001 by CHF, Inc.

12.
Eur J Cell Biol ; 79(9): 583-93, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11043399

RESUMO

We have analysed the expression of cadherin/catenin complex molecules in PC C13 rat thyroid cells transformed in vitro with different oncogenes. No significant downregulation of either E-cadherin, alpha-, beta- and gamma-catenin was detected following the introduction of activated forms of myc, adenovirus E1A, ras, raf, myc + ras, E1A + raf. However, ras- and raf-transformed PC C13 cells showed altered adherens junctions. An altered distribution of cadherin/catenin complexes characterized by radially oriented membrane spikes perpendicular to cell edges was the most prominent feature evidenced by immunofluorescence. No beta1 integrin localization was observed in areas where this altered pattern of E-cadherin expression was detected. However, beta1 integrin subunit expression was detected at areas of cell-cell contact where E-cadherin showed a normal pattern of expression. Furthermore, ras- and raf-transformed PC C13 cells showed the ability to migrate in collagen gels, in contrast to their normal untransformed counterpart. Overexpression of beta1 integrin was found to restore normal E-cadherin localization at cell-cell contacts and to partially inhibit the ability to migrate in collagen gels. Finally, two cell lines obtained by ras transformation in vivo, and derived from a rat primary thyroid carcinoma (TK6) and its lung metastasis (MPTK6), were found to have lost gamma-catenin expression. TK6 lost also E-cadherin expression and membrane localization of alpha-catenin. These results suggest that: i) in vitro thyroid cell transformation is associated to a change in cadherin/catenin complexes distribution rather than to a decrease in expression; ii) in vivo transformation is associated to the loss of expression of some of these molecules likely due to tumor progression; iii) alterations in beta1 integrin subunit expression can result in changes in cadherin/catenin function thus implying that an integrin-cadherin synergy may exist in thyroid cells.


Assuntos
Caderinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Células Epiteliais/metabolismo , Integrina beta1/metabolismo , Glândula Tireoide/citologia , Transativadores , Proteínas E1A de Adenovirus/genética , Animais , Western Blotting , Caderinas/análise , Caderinas/genética , Comunicação Celular/fisiologia , Linhagem Celular Transformada , Movimento Celular/fisiologia , Colágeno , Proteínas do Citoesqueleto/análise , Proteínas do Citoesqueleto/genética , Desmoplaquinas , Células Epiteliais/química , Células Epiteliais/citologia , Imunofluorescência , Géis , Expressão Gênica/fisiologia , Genes myc , Genes ras , Integrina beta1/análise , Integrina beta1/genética , Proteínas Oncogênicas v-raf , Ratos , Proteínas Oncogênicas de Retroviridae/genética , Vírus do Sarcoma Murino/genética , alfa Catenina , beta Catenina , gama Catenina
13.
J Biol Chem ; 275(1): 303-11, 2000 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-10617619

RESUMO

cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases (PKAs), typically determined by their specific regulatory subunits. We describe changes in the cAMP signal transduction pathway during cell cycle progression in synchronized rat thyroid cells. Both PKA type II (PKAII) localization and nuclear cAMP signaling are significantly modified during G(0) and G(1)-S transitions. G(1) is characterized by PKA activation and amplified cAMP signal transduction. This is associated with a decrease in the concentration of RI and RII regulatory subunits and enhanced anchoring of PKAII to the Golgi-centrosome region. Just prior to S, the cAMP pathway is depressed. Up-regulation of the pathway by exogenous cAMP in G(1) inhibited the subsequent decay of the Cdk inhibitor p27 and delayed the onset of S phase. Forced translocation of endogenous PKAII to the cytosol down-regulated cAMP signaling, advancing the timing of p27 decay and inducing premature exit from G(1). These data indicate that membrane-bound PKA amplifies the transduction of cAMP signals in G(1) and that the length of G(1) is influenced by cAMP-PKA.


Assuntos
Proteínas de Ciclo Celular , Ciclo Celular/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Glândula Tireoide/citologia , Proteínas Supressoras de Tumor , Animais , Transporte Biológico , Compartimento Celular , Núcleo Celular/enzimologia , Proteína Quinase Tipo II Dependente de AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico/isolamento & purificação , Inibidor de Quinase Dependente de Ciclina p27 , Quinases Ciclina-Dependentes/metabolismo , Citosol/enzimologia , Regulação para Baixo , Fase G1/fisiologia , Membranas/enzimologia , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos , Transdução de Sinais
14.
Int J Radiat Oncol Biol Phys ; 43(5): 1055-60, 1999 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-10192355

RESUMO

PURPOSE: To assess treatment outcome for patients with locally advanced or recurrent gynecological malignancies treated with continuous low-dose-rate (LDR) remote afterloading brachytherapy using the Martinez Universal Perineal Interstitial Template (MUPIT). MATERIALS AND METHODS: Between 7/85 and 6/94, 69 patients with either locally advanced or recurrent malignancies of the cervix, endometrium, vagina, or female urethra were treated by 5 different physicians using the MUPIT with (24 patients) or without (45 patients) interstitial hyperthermia. Fifty-four patients had no prior treatment with radiation and received a combination of external beam irradiation (EBRT) and an interstitial implant. The combined median dose was 71 Gy (range 56-99 Gy), median EBRT dose was 39 Gy (range 30-74 Gy), and the median implant dose was 32 Gy (range 17-40 Gy). Fifteen patients with prior radiation treatment received an implant alone. The total median dose including previous EBRT was 91 Gy (range 70-130 Gy) and the median implant dose was 35 Gy (range 25-55 Gy). RESULTS: With a median follow-up of 4.7 yr in survivors, the 3-yr actuarial local control (LC), disease-specific survival (DSS), and overall survival (OS) for all patients was 60%, 55%, and 41% respectively. The clinical complete response rate was 78% and in these patients the 3-year actuarial LC, DSS, and OS was 78%, 79%, and 63% respectively. On univariate analysis for local control, disease volume and hemoglobin were found to be statistically significant. On multivariate analysis, however, only disease volume remained significant (p = 0.011). There was no statistically significant difference in local control whether patients had received any prior treatment with radiation (p = 0.34), had recurrent disease (p = 0.13), or which physician performed the implant (p = 0.45). The grade 4 complication rate (small bowel obstruction requiring surgery, fistulas, soft tissue necrosis) for all patients was 14%. With a dose rate less than 70 cGy/hour, the grade 4 complication rate was 3% vs. 24% with dose rate > or = 70 cGy/hour (p = 0.013). CONCLUSION: Patients with locally advanced or recurrent gynecological malignancies treated with the remote afterloader LDR MUPIT applicator can expect reasonable rates of local control that are not operator-dependent. Complication rates with this approach are acceptable and appear to be related to the dose rate.


Assuntos
Braquiterapia/métodos , Neoplasias dos Genitais Femininos/radioterapia , Radioisótopos de Irídio/uso terapêutico , Recidiva Local de Neoplasia/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias Uretrais/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Braquiterapia/efeitos adversos , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Neoplasias Uretrais/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Neoplasias Vaginais/patologia , Neoplasias Vaginais/radioterapia
15.
Am Heart J ; 137(2): 322-31, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9924167

RESUMO

OBJECTIVES: Because of recent changes in the treatment of unstable angina, we wanted to reassess the short-term prognostic value of clinical and echocardiographic variables. METHODS: This was an observational, prospective study that included 1038 nonselected consecutive patients admitted to coronary care units for unstable angina. RESULTS: Baseline characteristics were age 60.18 +/- 16 years, history of prior myocardial infarction in 336 patients (32%), and a history of previous angina in 817 patients (78.7%). Angina during the 48 hours before admission was observed in 1004 patients (96.7%) and ST-segment changes on admission electrocardiogram occurred in 385 patients (37%). In-hospital treatment consisted of nitrates in 81.4% of patients, aspirin in 88.6%, beta-blockers in 71%, intravenous heparin in 34.5%, subcutaneous heparin in 23%, and angioplasty or coronary artery bypass grafting in 25.1%. After admission, angina occurred in 443 patients (40.8%), refractory angina in 223 patients (21.5%), and death or myocardial infarction in 84 patients (8.1%). At admission, the independent predictors of myocardial infarction or death identified by multivariate logistic regression analysis were ST-segment depression (odds ratio [OR] 2.13, 95% confidence interval [CI] 1.23 to 3.68, P =.006), prior angina (OR 2.23, 95% CI 0.98 to 5.05, P =.05), number of episodes of angina within the previous 48 hours (OR 1.63, 95% CI 0.98 to 2.70, P =.05), and history of smoking (OR 0.69, 95% CI 0.56 to 0.85, P =.004). Age greater than 65 years (OR 1.49, 95% CI1.09 to 2.03, P = 0.03) was significantly related to in-hospital death. The area under the receiver operating characteristic curve for application of this model was 0.59. Sensitivity was 80% with a specificity of only 33%. Refractory angina after admission showed a strong relation with an adverse short-term outcome. CONCLUSIONS: With current therapy, clinical and electrocardiographic variables provide useful information about the short-term outcome of unstable angina. However, this model has low specificity to identify high-risk patients. Future studies about the incremental value of the new serum markers such as troponin T and C-reactive protein to assist in identification of high-risk patients are necessary.


Assuntos
Angina Instável/epidemiologia , Idoso , Angina Instável/mortalidade , Angina Instável/terapia , Eletrocardiografia , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prognóstico , Estudos Prospectivos , Curva ROC , Recidiva , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
16.
Acta gastroenterol. latinoam ; 29(5): 307-12, 1999. ilus, tab, graf
Artigo em Espanhol | LILACS | ID: lil-252824

RESUMO

Antecedentes. La isquemia pancreática parece ser responsible de la transición de formas edematosas a necrohemorrágicas en la pancreatitis aguda. La vaso constricción simpática, vía plexo celíaco, tiene importante papel en su patogénesis. Objetivo: Determinar los efectos del bloqueo del plexo celíaco en un modelo experimental de pancreatitis aguda biliar. Método: Luego de pancreatectomia distal, inyección de bilis en el conducto excretor pancreático en 28 perros mestizos adultos. Bloqueo del plexo celíaco en bupivacaína (*) en el grupo experimental B. manteniendo a otro grupo sin bloqueo (grupo testigo). Estudio histopatológico a las 72 hs. Resultados: El grupo experimental B desarrolló formas las leves del PA, mientras que en grupo A evolucionó hacia las formas mas graves. Conclusiones: Los resultados sugieren que el bloqueo del plexo celíaco con bupivacaína puede previnir la evolución hacia la forma necrohemorrágica en la PA experimental en el perro.


Assuntos
Animais , Cães , Anestésicos Locais , Bloqueio Nervoso Autônomo , Bupivacaína , Plexo Celíaco , Pancreatite , Doença Aguda
17.
Am J Cardiol ; 81(11): 1286-91, 1998 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9631964

RESUMO

One hundred four patients presenting with acute myocardial infarction < 24 hours after onset were randomized to 2 groups: group I (n = 52) was treated with balloon angioplasty followed electively with Gianturco Roubin II stents, and group II was treated with conventional balloon angioplasty alone (n = 52). All lesions were suitable for stenting. Baseline clinical, demographic, and angiographic characteristics were similar in the 2 groups. Procedural success was defined as no laboratory death or emergent coronary bypass, Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow after the procedure in a culprit vessel, and a residual stenosis < or = 30% for coronary angioplasty and < 20% for stent. Procedural success was 98% in group I versus 94.2% in group II, p = NS. Thirteen patients in group II (25%) had bailout stenting during the initial procedure. Adverse in-hospital events including either death, nonelective coronary bypass, recurrent ischemia, and reinfarction occurred in 3.8% in group I versus 19.2% in group II, p = 0.03. Repeat angiography performed routinely before hospital discharge revealed TIMI 3 flow in the infarct-related artery in 98% in group I versus 83% in group II, p < 0.03. At late follow-up, event-free survival was significantly better in the stent (83%) than in the coronary angioplasty (65%) group (p = 0.002). The procedural in-hospital and late outcomes of this randomized study demonstrate that balloon angioplasty followed electively by coronary stents can be used as the primary modality for patients undergoing coronary interventions for acute myocardial infarction, increasing TIMI 3 flow, reducing in-hospital adverse events, and improving late outcome compared with balloon angioplasty alone.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Ponte de Artéria Coronária , Mortalidade Hospitalar , Infarto do Miocárdio/terapia , Stents , Adulto , Idoso , Circulação Coronária/fisiologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Radiografia , Recidiva , Retratamento , Resultado do Tratamento
18.
Int J Radiat Oncol Biol Phys ; 41(1): 13-9, 1998 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9588912

RESUMO

PURPOSE: High-dose rate (HDR) applicators for uterine cervix brachytherapy are used with increasing frequency. Because multiple HDR fractions are required for treatment, the applicator position reproducibility is of most importance. To study this effect, the clinical data from patients with uterine cervix cancer were examined retrospectively to evaluate the interfraction geometric variation of the HDR applicator and its potential treatment impact. METHODS AND MATERIALS: Eighteen patients with invasive cervical cancer who were treated with definitive radiotherapy at William Beaumont Hospital were included in the study. Patients were treated with 45-50.4 Gy megavoltage external beam to the pelvis, and 35 Gy to the prescription point A from 7 fractions of HDR brachytherapy. The 3-dimensional (3D) interfraction geometrical variation of the ring and tandem (R & T) applicator was measured using predefined reference points in the 7 sets of orthogonal simulation films obtained prior to each HDR application. Spatial reproducibility of the R & T insertion and time-trend of the R & T position variation related to patient's anatomy during the treatment course were analyzed with respect to different groups of patients who had either early or advanced disease. RESULTS: The translational variation of the applicator position for all patients was 6.5, 5.9, and 7.7 mm (one standard deviation), respectively, in the patient's superior-to-inferior (SI), right-to-left lateral (RL), and anterior-to-posterior (AP) direction. The rotational variation was 3.4, 4.6, and 6.0 degrees (one standard deviation) in the patient's coronal, transverse, and sagittal planes. When the patients were grouped based on early disease or advanced disease, the latter demonstrated substantially larger variation (factor of 2) in the applicator position than the former. Furthermore, the time-trend of position variation was observable for both groups of patients. The variations occurred primarily during the first 3 fractions. CONCLUSIONS: Based on the good spatial reproducibility observed in our study, the current clinical procedure for the HDR R & T applicator placement is reliable. Positional reproducibility of the R & T applicator is highly dependent upon the size of tumor volume, which, in turn, deviates the applicator during the early course of HDR brachytherapy. Attention to the construction of the midline block is of paramount importance.


Assuntos
Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Braquiterapia/instrumentação , Feminino , Humanos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes
19.
Int J Radiat Oncol Biol Phys ; 38(4): 755-9, 1997 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-9240643

RESUMO

PURPOSE: To determine the value of breast ultrasonography (US) in defining the lumpectomy cavity for patients treated with interstitial brachytherapy. METHODS AND MATERIALS: In March 1993, a protocol of low dose rate (LDR) interstitial brachytherapy as the sole radiation modality in selected patients with early breast cancer was initiated at William Beaumont Hospital. To date, 60 patients have been entered in this protocol, and 38 have undergone US assisted placement of interstitial brachytherapy needles. The lumpectomy cavity was outlined in all dimensions and corresponding skin marks were placed for reference at time of implantation. These US dimensions were compared to the physician's clinical estimate of the location of the lumpectomy cavity, the patient's presurgical mammogram, and the position of the surgical scar. In the intraoperative setting, the dimensions of the lumpectomy cavity were also obtained and the placement of the deep plane of interstitial needles was verified by US. RESULTS: The full extent of the lumpectomy cavity was underestimated by clinical examination (physical exam, operative report, mammographic information and location of the surgical scar) in 33 of 38 patients (87%). The depth to the chest wall was also incorrectly estimated in 34 (90%) patients when compared to US examination. Intraoperatively, US was performed in nine patients and was useful in verifying the accurate placement of the deepest plane of interstitial brachytherapy needles. In 7 of 9 patients (75%), clinical placement of needles did not ensure adequate coverage of the posterior extent of the lumpectomy cavity as visualized by intraoperative US. CONCLUSIONS: In breast cancer patients considered for interstitial brachytherapy, US appears to be a more accurate means of identifying the full extent of the lumpectomy cavity when compared to clinical estimates. In addition, US allows real-time verification of needle placement in the intraoperative setting.


Assuntos
Braquiterapia/métodos , Neoplasias da Mama/radioterapia , Mastectomia Segmentar , Ultrassonografia de Intervenção , Ultrassonografia Mamária , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Humanos
20.
J Am Coll Cardiol ; 28(6): 1488-92, 1996 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-8917262

RESUMO

OBJECTIVES: This study sought to determine whether the response to amrinone in patients with severe baseline left ventricular dysfunction can predict improvement in left ventricular ejection fraction after coronary artery bypass graft surgery. BACKGROUND: Previous studies have suggested that the inotropic response to dobutamine can identify viable myocardium in the setting of chronic coronary disease and left ventricular dysfunction. However, increased oxygen demand stimulated by dobutamine can lead to superimposition of ischemia on the hibernating state, potentially confounding interpretation of results. Amrinone is an inotropic agent that does not critically augment myocardial oxygen demand and may be useful for identification of hibernating myocardium in the chronically ischemic state. METHODS: Forty-four consecutive patients with coronary artery disease and left ventricular ejection fraction < 40% referred for coronary artery bypass graft surgery underwent amrinone stimulation (1 mg/kg body weight). Left ventricular ejection fraction was determined before amrinone stimulation, 20 min after infusion and 21 days after bypass surgery. RESULTS: Baseline ejection fraction was 28 +/- 7% (mean +/- SD). Ejection fraction increased to 35 +/- 5% after amrinone stimulation (p < 0.0001) and to 33 +/- 6% after bypass surgery (p < 0.0001). Postbypass ejection fraction was significantly correlated with postamrinone ejection fraction (r = 0.65, p < 0.0001). Furthermore, the change in ejection fraction from baseline to after bypass surgery was highly correlated with the change in ejection fraction after amrinone stimulation (r = 0.75, p < 0.0001). Of 13 patients with an increase in ejection fraction > or = 10% after amrinone, all 13 had an increase of at least 8% and 11 (85%) of 13 had an increase > or = 10% after bypass surgery. In contrast, of 31 patients with an increase in ejection fraction < 10% after amrinone, only 2 (6%) had an increase > or = 10% (p < 0.0001) and 28 (90%) of 31 had an increase < 5% after bypass surgery. CONCLUSIONS: Augmentation of myocardial contraction by amrinone in patients with chronic coronary artery disease and severe baseline left ventricular dysfunction predicts improvement in left ventricular ejection fraction after coronary artery bypass graft surgery.


Assuntos
Amrinona , Cardiotônicos , Ponte de Artéria Coronária , Doença das Coronárias/fisiopatologia , Doença das Coronárias/cirurgia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Amrinona/farmacologia , Cardiotônicos/farmacologia , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
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