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1.
Arch Gynecol Obstet ; 307(6): 1781-1788, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35704114

RESUMO

PURPOSE: To evaluate women's choice in the method of labour induction between oral misoprostol, PGE2 pessary and the Foley catheter. To compare women's satisfaction according to their choice and to identify factors associated with patient satisfaction. METHODS: We conducted a comparative, prospective cohort study of 520 women who chose their preferred method for labour induction, in a French tertiary hospital, from July 2019 to October 2020. Before and after the delivery, they were asked to argue their choice and to evaluate their satisfaction through the use of questionnaires. The primary outcome was global level of satisfaction. RESULTS: Of the 520 women included, 67.5% of women chose oral misoprostol compared to 21% PGE2 pessary and 11.5% Foley catheter. Regarding global satisfaction, we found no significant difference between the three groups: 78.4%, 68.8% and 71.2% (p = 0.107) for, respectively, oral misoprostol, PGE2 pessary and Foley catheter. Factors that seem to improve women's satisfaction were nulliparity (aOR = 2.03, 95% CI [1.19-3.53]), delivery within 24 h after the start of induction (aOR = 3.46, 95% CI [2.02-6.14]) and adequate information (aOR = 4.21, 95% CI [1.869.64]). Factors associated with lower satisfaction rates were postpartum haemorrhage (aOR = 0.51, 95% CI [0.30-0.88]) and caesarean section (aOR = 0.31, 95% CI [0.17-0.54]). CONCLUSION: Women satisfaction rates were not different between the three methods, when chosen by the patients themselves. These finding should encourage caregivers to promote shared decision making when possible. TRIAL REGISTRATION: The protocol was approved by the French ethics committee for research in obstetrics and gynaecology (CEROG, reference number 2019-OBS-0602) on 1st June 2019.


Assuntos
Misoprostol , Ocitócicos , Gravidez , Feminino , Humanos , Masculino , Dinoprostona , Cesárea , Estudos Prospectivos , Trabalho de Parto Induzido/métodos , Maturidade Cervical
2.
Eur J Nucl Med Mol Imaging ; 47(5): 1252-1260, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31915897

RESUMO

PURPOSE: The aim of our study was to comprehensively evaluate the most valuable metabolic parameters of cervical tumours and pelvic lymph nodes (PLN) by FDG-PET/CT to predict para-aortic lymph node (PALN) metastasis and stratify patients for surgical staging. METHODS: The study included patients with locally advanced cervical cancer, negative PALN uptake on preoperative FDG-PET/CT, and para-aortic lymphadenectomy. Two senior nuclear medicine physicians expert in gynaecologic oncology reviewed all PET/CT exams, and extracted tumour SUVmax, MTV, and TLG, as well as PLN. Prognostic parameters of PALN involvement were identified using ROC curves and logistic regression analysis. RESULTS: One hundred and twenty-five consecutive locally advanced cervical cancer patients were included. The FDG-PET/CT false-negative rate was, respectively, 27.7% (13/47) and 5.1% (4/78) in patients with and without FDG-PET/CT PLN uptake. The AUC of cervical tumour size, SUVmax, MTV, and TLG was, respectively, 0.75 (0.62-0.87), 0.59 (0.44-0.76), 0.75 (0.60-0.90), and 0.71 (0.56-0.86). The AUC of PLN size, SUVmax, SUVmean, PLN SUVmax/Tumour SUVmax ratio, MTV, and TLG was, respectively, 0.57 (0.37-0.78), 0.82 (0.68-0.95), 0.77 (0.61-0.94), 0.85 (0.72-0.98), 0.69 (0.51-0.87), and 0.74 (0.57-0.91). The metabolic parameter showing the best trade-off between sensitivity and specificity to predict PALN involvement was the ratio between PLN and tumour SUVmax. CONCLUSION: The risk of PALN metastasis in FDG-PET/CT negative PLN patients is very low, so para-aortic lymphadenectomy does not seem justified. In patients with preoperative PLN uptake on FDG-PET/CT, surgical staging led to treatment modification in more than 25% of cases and should therefore be performed. Patients with more than one positive PLN and high PLN metabolic activity are at high risk of para-aortic extension and recurrence. Further prospective evaluation is required to consider intensified treatment modalities without prior PALN dissection.


Assuntos
Neoplasias do Colo do Útero , Feminino , Fluordesoxiglucose F18 , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
3.
Phys Rev Lett ; 122(15): 155301, 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31050536

RESUMO

We study the quantum sine-Gordon model within a nonperturbative functional renormalization-group approach (FRG). This approach is benchmarked by comparing our findings for the soliton and lightest breather (soliton-antisoliton bound state) masses to exact results. We then examine the validity of the Lukyanov-Zamolodchikov conjecture for the expectation value ⟨e^{(i/2)nßφ}⟩ of the exponential fields in the massive phase (n is integer and 2π/ß denotes the periodicity of the potential in the sine-Gordon model). We find that the minimum of the relative and absolute disagreements between the FRG results and the conjecture is smaller than 0.01.

4.
Ann Oncol ; 28(10): 2526-2532, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961833

RESUMO

BACKGROUND: In the phase III LUX-Head & Neck 1 (LUX-H&N1) trial, second-line afatinib significantly improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Here, we evaluated association of prespecified biomarkers with efficacy outcomes in LUX-H&N1. PATIENTS AND METHODS: Randomized patients with R/M HNSCC and progression following ≥2 cycles of platinum therapy received afatinib (40 mg/day) or methotrexate (40 mg/m2/week). Tumor/serum samples were collected at study entry for patients who volunteered for inclusion in biomarker analyses. Tumor biomarkers, including p16 (prespecified subgroup; all tumor subsites), EGFR, HER2, HER3, c-MET and PTEN, were assessed using tissue microarray cores and slides; serum protein was evaluated using the VeriStrat® test. Biomarkers were correlated with efficacy outcomes. RESULTS: Of 483 randomized patients, 326 (67%) were included in the biomarker analyses; baseline characteristics were consistent with the overall study population. Median PFS favored afatinib over methotrexate in patients with p16-negative [2.7 versus 1.6 months; HR 0.70 (95% CI 0.50-0.97)], EGFR-amplified [2.8 versus 1.5 months; HR 0.53 (0.33-0.85)], HER3-low [2.8 versus 1.8 months; HR 0.57 (0.37-0.88)], and PTEN-high [1.6 versus 1.4 months; HR 0.55 (0.29-1.05)] tumors. Afatinib also improved PFS in combined subsets of patients with p16-negative and EGFR-amplified tumors [2.7 versus 1.5 months; HR 0.47 (0.28-0.80)], and patients with p16-negative tumors who were EGFR therapy-naïve [4.0 versus 2.4 months; HR 0.55 (0.31-0.98)]. PFS was improved in afatinib-treated patients who were VeriStrat 'Good' versus 'Poor' [2.7 versus 1.5 months; HR 0.71 (0.49-0.94)], but no treatment interaction was observed. Afatinib improved tumor response versus methotrexate in all subsets analyzed except for those with p16-positive disease (n = 35). CONCLUSIONS: Subgroups of HNSCC patients who may achieve increased benefit from afatinib were identified based on prespecified tumor biomarkers (p16-negative, EGFR-amplified, HER3-low, PTEN-high). Future studies are warranted to validate these findings. CLINICAL TRIAL REGISTRATION: NCT01345682.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Quinazolinas/administração & dosagem , Administração Intravenosa , Administração Oral , Afatinib , Antimetabólitos Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/sangue , Biópsia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço
5.
Gynecol Obstet Fertil Senol ; 50(7-8): 505-510, 2022.
Artigo em Francês | MEDLINE | ID: mdl-35288365

RESUMO

OBJECTIVES: To identify risk factors for cesarean section of the second twin after vaginal delivery of the first twin. METHODS: Case-control study conducted between 2004 and 2018 in a tertiary center, CHU Toulouse. Cases were women with twin pregnancy who had vaginal delivery of the first twin and emergency cesarean of the second twin. Controls were women with twin pregnancy who delivered both twins vaginally. Deliveries before 24 weeks of gestation, birth weight of less than 500 grams, fetal death in utero, terminations of pregnancy and delayed delivery were excluded. The association between potential risk factors and cesarean delivery of the second twin was analyzed using multivariable logistic regression. RESULTS: Twenty-four patients who had vaginal delivery of the first twin and emergency cesarean of the second twin and 48 patients who delivered both twins vaginally were included. Neonatal morbidity was increased in the group of women who had an emergency cesarean of the second twin. In multivariable analysis, overweight (OR=10.5 [95% CI: 1.78-62.03] for women with body mass index above 25 compared to women with body mass index below 25), weight gain during pregnancy (OR=1.27 [95% CI: 1.01-1.48] for each kilogram) and preterm labor (OR=4,43 [IC 95%:1,10-17,80]) were associated with significantly increased risk of cesarean section of the second twin. CONCLUSION: Overweight and weight gain during pregnancy are associated with increased risk for cesarean section of the second twin.


Assuntos
Cesárea , Sobrepeso , Estudos de Casos e Controles , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Aumento de Peso
6.
Opt Express ; 16(12): 8480-6, 2008 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-18545562

RESUMO

We report a novel hybrid integrated optic device consisting of AlGaInAs/InP electroabsorption modulators and a four-arm silica-on-silicon planar lightwave circuit optical interferometer. The device is designed for generation of high spectral efficiency optical modulation formats. We demonstrate generation of 21.4 Gb/s quadrature phase shift keyed optical signals with electrical data drives of 2V(pp) amplitudes, achieving a bit error rate of 10(-9) with the required optical signal to noise ratio of ~18 dB in a 0.1 nm resolution bandwidth.


Assuntos
Eletrônica/instrumentação , Modelos Teóricos , Óptica e Fotônica/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Transdutores , Simulação por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de Radiação
7.
Nat Commun ; 8: 14464, 2017 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-28224994

RESUMO

The superconductor-insulator transition (SIT) is considered an excellent example of a quantum phase transition that is driven by quantum fluctuations at zero temperature. The quantum critical point is characterized by a diverging correlation length and a vanishing energy scale. Low-energy fluctuations near quantum criticality may be experimentally detected by specific heat, cp, measurements. Here we use a unique highly sensitive experiment to measure cp of two-dimensional granular Pb films through the SIT. The specific heat shows the usual jump at the mean field superconducting transition temperature marking the onset of Cooper pairs formation. As the film thickness is tuned towards the SIT, is relatively unchanged, while the magnitude of the jump and low-temperature specific heat increase significantly. This behaviour is taken as the thermodynamic fingerprint of quantum criticality in the vicinity of a quantum phase transition.

8.
Cancer Res ; 54(24): 6325-9, 1994 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-7987822

RESUMO

Detection of sequence-specific DNA damage induced by antitumor alkylating agents might provide a mechanism for detecting and discriminating damage specific to one or more of these drugs. Using repetitive primer-extension and human alphoid DNA as a substrate, lesions specific for an activated form of cyclophosphamide, 4-hydroperoxycyclophosphamide, were detected at 32 of 33 guanines within a 200-base pair region in DNA from cells treated in culture. There was a marked variation in lesion site intensity among affected guanines. For instance, guanines flanked by cytosine were weak sites of 4-hydroperoxycyclophosphamide-induced damage. Damage at bases other than guanine induced by cisplatin, UV irradiation, and adozelesin were compared to drug-DNA lesions induced by 4-hydroperoxycyclophosphamide. Using this method it was possible to detect, and at some sites distinguish, between cyclophosphamide- and cisplatin-induced DNA damage within WBC DNA from a patient treated with both agents. There was a different damage pattern for DNA derived from cells treated in culture compared to DNA derived from the patient sample.


Assuntos
Cisplatino/farmacologia , Ciclofosfamida/análogos & derivados , Dano ao DNA/genética , DNA de Neoplasias/efeitos dos fármacos , Indóis , Sequência de Bases/efeitos dos fármacos , Sequência de Bases/efeitos da radiação , Benzofuranos , Ácidos Cicloexanocarboxílicos/farmacologia , Cicloexenos , Ciclofosfamida/farmacologia , DNA de Neoplasias/genética , DNA de Neoplasias/efeitos da radiação , Relação Dose-Resposta a Droga , Duocarmicinas , Humanos , Dados de Sequência Molecular , Células Tumorais Cultivadas
10.
Int J Oncol ; 3(2): 197-203, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21573348

RESUMO

Oxygen profiles of the rat mammary 13672 carcinoma were determined using a pO2 histograph prior to treatment and 24 h and 48 h after i.p. administration of a single dose of cyclophosphamide (300 mg/kg). The tumors were severely hypoxic at 24 h post the administration of cyclophosphamide. There was little increase in oxygenation of the tumors at 48 h post therapy compared with 24 h post therapy indicating that reoxygenation after cyclophosphamide was occurring very slowly in this tumor. Carbogen breathing improved the oxygenation of the tumors under each of the conditions studied. Administration of the perflubron emulsion (8 ml/kg) produced little or no change in the oxygenation of the tumors under normal air breathing conditions. However, the addition of carbogen breathing to administration of the perflubron emulsion increased the oxygenation of the tumors to levels equal to or greater than carbogen breathing at the mean/median pO2's. Perhaps most significantly, administration of the perflubron emulsion with carbogen breathing increased the oxygenation of the most hypoxic regions of the tumors but carbogen breathing alone did not. The growth delay of the Lewis lung carcinoma increased with increasing dose.of the perflubron emulsion along with cyclophosphamide (3 x 150 mg/kg) and carbogen breathing (6 h). This combination treatment was most effective when the cyclophosphamide was prepared in the perflubron emulsion. The number of lung metastases decreased in a manner parallel with increased efficacy of the treatment toward the primary tumor.

11.
Int J Oncol ; 2(1): 13-21, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21573510

RESUMO

Oxygen tension measurements were made in three tumors: (i) the murine FSaII fibrosarcoma, (ii) the rat 9L gliosarcoma and (iii) the rat 13672 mammary adenocarcinoma using a pO2 histograph. Tumor oxygenation measurements were made while the animals breathed air or breathed carbogen (95% oxygen/5% carbon dioxide). Pentoxifylline or a perflubron emulsion was administered to the animals and tumor oxygen measurements were repeated under both breathing conditions. Both pentoxifylline and the perflubron emulsion improved the oxygenation of the FSaII fibrosarcoma under air breathing conditions but did not alter the oxygen profiles of either rat tumor compared with air breathing alone. Carbogen breathing increased the oxygenation of all tumors. Pentoxifylline administration did not change the oxygen profiles of the tumors under carbogen breathing conditions but administration of the perflubron emulsion increased the oxygenation of all three tumors under carbogen breathing conditions compared with carbogen breathing alone. Co-administration of pentoxifylline and the perflubron emulsion enhanced the radiation response of the Lewis lung tumor to daily fractionated radiation under air breathing conditions with a dose modifying factor of 1.65 and under carbogen breathing conditions with a dose modifying factor of 2.25. Over a range of perflubron emulsion doses, pentoxifylline increased the growth delay of the Lewis lung tumor in a constant manner. These results indicate that pentoxifylline and the perflubron emulsion have the largest impact on the oxygenation of more hypoxic tumors and that administration of the perflubron emulsion/carbogen breathing is the most effective means of increasing tumor oxygenation and radiation response.

12.
Int J Oncol ; 2(2): 145-53, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21573528

RESUMO

The nonsteroidal antiinflammatory drugs that inhibit cyclooxygenase block the formation of prostanoids in vivo. These agents may be useful as modulators of cytotoxic anticancer therapies. EMT-6 mouse mammary carcinoma cells growing in culture were exposed for 1 h or 24 h to eleven different nonsteroidal antiinflammatory agents or acetaminophen. None of these drugs was very cytotoxic. A concentration of 50muM of the nonsteroidal antiinflammatory drugs or acetaminophen was chosen for modulator combination studies with the antitumor alkylating agents CDDP, L-PAM, BCNU and 4-HC in cell culture. Several of the modulators protected the EMT-6 cells from the cytotoxicity of the antitumor alkylating agents; however, diflunisal, sulindac, indomethacin, acetaminophen and in some cases ibuprofen and tolmetin were positive modulators of the antitumor alkylating agents under the cell culture conditions tested. EMT-6 tumor cell survival studies and bone marrow CFU-GM survival studies were carried out with seven of the modulators and various doses of cyclophosphamide. Tolmetin, ibuprofen, sulindac, piroxicam and diflunisal in combination with cyclophosphamide produced increased tumor cell killing compared with cyclophosphamide alone without marked changes in toxicity to the bone marrow derived CFU-GM. In EMT-6 tumor growth delay experiments, none of the six modulators tested affected the growth of the tumors; however, tolmetin, ibuprofen, diflunisal and sulindac increased the tumor growth delay obtained with standard dose-schedules of cyclophosphamide or CDDP. When minocycline, a collagenase inhibitor, was added to treatment regimens including diflunisal or sulindac and either cyclophosphamide, CDDP or L-PAM further increases in tumor growth delay were obtained especially when L-PAM was the cytotoxic therapeutic agent. The number of lung metastases and the percentage lung metastases with diameters >3 mm were reduced by treatment with the modulator combinations alone and further reduced with the addition of the antitumor alkylating agents. These results indicate that agents which inhibit signaling pathways among tumor cells and between tumor cells and normal cells can be useful additions to cytotoxic therapies.

13.
J Cancer Res Clin Oncol ; 120(10): 593-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7929530

RESUMO

Rat 13672 mammary carcinoma tumors were grown subcutaneously in the hind legs of female Fischer 344 rats to a volume of about 1 cm3. Tumor oxygenation was measured using an Eppendorf PO2 histograph. Tumor oxygen measurements were made under four conditions: (a) normal air breathing, (b) carbogen breathing, (c) after intravenous administration of a perflubron emulsion (8 ml/kg) with air breathing and (d) after intravenous administration of a perflubron emulsion (8 ml/kg) with carbogen breathing. Tumor oxygenation was examined without treatment or 24 h and 48 h after treatment with cyclophosphamide (300 mg/kg, i.p.) or cisplatin (8 mg/kg, i.p.] or after the fifth dose of a daily regimen of 3-Gy irradiation (5 x 3 Gy). Under normal air-breathing conditions 49% of the tumor had a PO2 < or = 670 Pa (5 mm Hg). The degree of hypoxia in the tumors increased after each treatment such that 24 h after treatment 65%-85% of the oxygen readings were < or = 670 Pa and 48 h after treatment 60%-74% of the oxygen readings were < or = 670 Pa. Administration of the perflubron emulsion/carbogen atmosphere increased the oxygen content of the tumors both without treatment and after each of the treatments. A knowledge of tumor oxygen content over the course of treatment and the ability to increase tumor oxygen should allow for the development of more rational treatment combinations and better treatment outcomes.


Assuntos
Dióxido de Carbono/farmacologia , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Fluorocarbonos/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Oxigênio/análise , Oxigênio/farmacologia , Radiossensibilizantes/farmacologia , Animais , Emulsões , Feminino , Hidrocarbonetos Bromados , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/radioterapia , Consumo de Oxigênio/efeitos dos fármacos , Pressão Parcial , Ratos , Ratos Endogâmicos F344
14.
J Cancer Res Clin Oncol ; 120(1-2): 85-90, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8270614

RESUMO

Tumor oxygen tensions were measured using a computer-controlled PO2 microelectrode in two preclinical solid tumor models, the rat 9L gliosarcoma and the rat 13672 mammary carcinoma. Tumor oxygenation profiles were determined under four conditions: (a) during normal air breathing, (b) during carbogen breathing, (c) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with normal air breathing and (d) after intravenous administration of a solution of ultrapurified polymerized bovine hemoglobin with carbogen breathing. Both tumors had severely hypoxic regions under normal air-breathing conditions. Although carbogen breathing increased the oxygenation of the better-oxygenated portions of the tumor, it made no impact on the severely hypoxic tumor regions. Administration of the hemoglobin solution was effective in increasing the oxygenation throughout both tumors under normal air-breathing conditions. The addition of carbogen breathing to administration of the hemoglobin solution eliminated severe hypoxia in the 9L gliosarcoma and markedly reduced the severely hypoxic regions of the 13672 mammary carcinoma. At 24 h after administration of the hemoglobin solution the 13672 mammary carcinoma showed greater hypoxia than before treatment, which was partially corrected with carbogen breathing.


Assuntos
Adenocarcinoma/terapia , Gliossarcoma/terapia , Hemoglobinas/uso terapêutico , Neoplasias Mamárias Experimentais/terapia , Consumo de Oxigênio , Adenocarcinoma/metabolismo , Administração por Inalação , Análise de Variância , Animais , Substitutos Sanguíneos/uso terapêutico , Dióxido de Carbono , Bovinos , Hipóxia Celular/fisiologia , Feminino , Gliossarcoma/metabolismo , Neoplasias Mamárias Experimentais/metabolismo , Oxigênio , Ratos , Ratos Endogâmicos F344
15.
Neuropeptides ; 3(3): 181-91, 1983 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16229161

RESUMO

Immunoreactive dynorphin (ir-Dyn) and opiate-like peptides (OLP) were measured in acid (HC1) extracts of human placenta by the use of an antibody to synthetic Dyn-(1-13) and of the displacement of [3H]-naloxone binding to rat brain homogenates, respectively. The placenta contained 57.6 pmoles per g of ir-Dyn and 134.4 pmoles per g of naloxone binding equivalents. After passage of the extract through cartridges of Sep Pak C18, half of the OLP was eluted with ir-Dyn at 35% acetonitrile (ACN), the rest being eluted at 60% ACN. Both fractions obtained from Sep Pak were chromatographed separately on Sephadex G-50, the OLP of the 35% ACN fraction coeluting with the ir-Dyn speak and that of the 60% ACN fraction being eluted at the same volume as synthetic beta-endorphin. Conversely, the fraction of OLP coeluting with synthetic leucine-enkephalin (Leu-Enk) in these two chromatographies was minimal. The Dyn-immunoreactive material was further purified by high pressure liquid chromatography on reverse phase micro-Bondapak C18 columns to give three distinct peaks corresponding to synthetic Dyn-(1-11), Dyn-(1-13) and Dyn-(1-12), respectively. Our results indicate that the human placenta contains several forms of ir-Dyn which account for about half of its endogenous OLP.


Assuntos
Dinorfinas , Placenta/química , Isoformas de Proteínas , Animais , Cromatografia em Gel , Dinorfinas/isolamento & purificação , Dinorfinas/metabolismo , Feminino , Humanos , Entorpecentes , Gravidez , Isoformas de Proteínas/isolamento & purificação , Isoformas de Proteínas/metabolismo , Radioimunoensaio , Ratos , Extratos de Tecidos/química , Extratos de Tecidos/metabolismo
16.
Cancer Chemother Pharmacol ; 36(5): 431-8, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7634385

RESUMO

Human 2008 ovarian carcinoma cells and the C13 CDDP-resistant subline and human MCF-7 breast carcinoma cells and the MCF-7/CDDP CDDP-resistant subline were exposed to L-buthionine-(S,R)-sulfoximine (50 microM) for 48 h prior to and during exposure for 1 h to the antitumor platinum complexes, cis-diamminedichloroplatinum(II), carboplatin or D,L-tetraplatin and/or to etanidazole (1 mM) for 2 h prior to and during exposure for 1 to the antitumor platinum complexes. These modulators alone did not significantly alter the cytotoxicity of CDDP toward either parental line. A twofold enhancement in cytotoxicity was observed with carboplatin in the 2008 cells and with D,L-tetraplatin in both parental lines with the single modulators. The modulator combination (buthionine sulfoximine/etanidazole) was very effective along with D,L-tetraplatin in both the MCF-7 parent and MCF-7/CDDP cell lines where at the higher platinum complex concentrations there was 1.5 to 3 logs increased killing of cells by the drug plus the modulators compared with the drug alone. Similarly, when C13 cells were exposed to CDDP (100 microM) or D,L-tetraplatin (100 microM) along with buthionine sulfoximine and etanidazole there was a 2-log increase in cell killing compared with exposure to the platinum complex alone. Treatment of each of the four cell lines with buthionine sulfoximine decreased both the non-protein and total sulfhydryl content of the cells. Treatment with the combination of modulators did not produce a further decrease in cellular sulfhydryl content compared with buthionine sulfoximine alone. The total sulfhydryl content in MCF-7 cells and 2008 cells exposed to buthionine sulfoximine and etanidazole was 58% and 31% of normal and the total sulfhydryl content of MCF-7/CDDP cells and C13 cells treated the same way was 54% and 23% of normal, respectively. DNA alkaline elution was used to assess the impact of exposure to the modulators, buthionine sulfoximine and etanidazole, alone and in combination on the cross linking of DNA by the antitumor platinum complexes in the MCF-7 and MCF-7/CDDP cell lines. Overall, the increases in DNA cross linking factors were greater in the MCF-7 cells than in the MCF-7/CDDP cells. These results indicate a possible clinical potential for this modulator combination.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Butionina Sulfoximina , Carboplatina/administração & dosagem , Resistência a Medicamentos , Etanidazol/administração & dosagem , Feminino , Humanos , Metionina Sulfoximina/administração & dosagem , Metionina Sulfoximina/análogos & derivados , Compostos Organoplatínicos/administração & dosagem , Células Tumorais Cultivadas
17.
Oncol Res ; 7(5): 237-43, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8534929

RESUMO

Although the antiangiogenic agent TNP-470 does not, in general, increase the cytotoxicity of anti-cancer therapies in cell culture, the antiangiogenic agents TNP-470 and minocycline individually and especially in combination have been shown to increase the tumor growth delay produced by several standard cytotoxic therapies in the Lewis lung carcinoma. In an effort to understand the mechanism by which the antiangiogenic agent combination TNP-470/minocycline potentiates the antitumor activity of cytotoxic therapeutic agents in vivo, the biodistribution of [14C]-cyclophosphamide and cis-diamminedichloroplatinum(II) was determined 6 h after cytotoxic drug administration in animals bearing Lewis lung carcinoma pretreated with TNP-470/minocycline and in animals without pretreatment. Higher levels of 14C and platinum were found in 9 tissues (including tumor) except blood in animals pretreated with TNP-470/minocycline. The increased drug levels in the tumors may be sufficient to account for the increased tumor growth delays observed previously. DNA alkaline elution of tumors from animals pretreated with TNP-470/minocycline showed increased DNA cross-linking by both cyclophosphamide and cis-diamminedichloroplatinum(II). The possible implications of these results are discussed.


Assuntos
Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Lewis/metabolismo , Cisplatino/farmacocinética , Ciclofosfamida/farmacocinética , Minociclina/farmacologia , Sesquiterpenos/farmacologia , Animais , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carmustina/farmacologia , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cicloexanos , Ciclofosfamida/análogos & derivados , Ciclofosfamida/farmacologia , DNA de Neoplasias/análise , DNA de Neoplasias/efeitos dos fármacos , Combinação de Medicamentos , Masculino , Melfalan/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , O-(Cloroacetilcarbamoil)fumagilol , Platina/análise , Células Tumorais Cultivadas
18.
In Vivo ; 8(1): 125-31, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8054502

RESUMO

Oxygen profiles of the rat mammary 13672 carcinoma were determined using a pO2 histograph prior to treatment and 24 hrs. and 48 hrs. after 2 or 5 fractions of 3 gray given once daily. The tumors were much more hypoxic at 24 hrs. post radiation therapy than prior to therapy. There was little increase in the oxygenation of the tumors at 48 hrs. post therapy compared with 24 hrs. post therapy indicating that reoxygenation was occurring very slowly in this tumor. Carbogen breathing improved the oxygenation of the tumors under each of the conditions studied. Administration of a perflubron emulsion (8 ml/kg) produced little or no change in the oxygenation of the tumors under normal air breathing conditions. However, with the addition of carbogen breathing to administration of the perflubron emulsion there was an increase in the mean/median pO2's of the tumors to levels equal to or greater than carbogen breathing alone. Perhaps most significantly administration of the perflubron emulsion with carbogen breathing increased the oxygenation of the most hypoxic regions of the tumors but carbogen breathing alone did not.


Assuntos
Dióxido de Carbono/farmacologia , Fluorocarbonos/farmacologia , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/radioterapia , Consumo de Oxigênio , Oxigênio/farmacologia , Radiossensibilizantes/farmacologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Hipóxia Celular , Feminino , Hidrocarbonetos Bromados , Microeletrodos , Oxigênio/análise , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/efeitos da radiação , Pressão Parcial , Ratos , Ratos Endogâmicos F344
19.
In Vivo ; 9(1): 11-8, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7669943

RESUMO

Tissue oxygen tensions were measured in the rat 9L gliosarcoma under conditions of normal air breathing or carbogen breathing and after intravenous administration of a hemoglobin solution with air breathing or carbogen breathing. Administration of the hemoglobin decreased the level of hypoxia in the tumors. Treatment of the animals with the antiangiogenic combination of TNP-470 and minocycline also increased tumor oxygenation compared with untreated controls. Treatment with the antiangiogenic agents along with administration of the hemoglobin solution/carbogen breathing decreased the hypoxic fraction (% pO2 readings < or = 5 mmHg) from 71 % to 30%. Treatment of the tumor-bearing animals with BCNU or adriamycin modestly reduced hypoxia in the tumors, while treatment with fractionated radiation markedly increased hypoxia in the tumors. Tumor growth delay was used to assess the response of the subcutaneous tumor to the various treatment combinations. There was a strong correlation between increased therapeutic response and decreased tumor hypoxia. Tumor growth delay from BCNU increased from 5.3 days to 16.4 days with TNP-470/-minocycline/hemoglobin solution/carbogen. Similarly, the tumor growth delay from adriamycin increased from 3.9 days to 17.0 days with TNP-470/minocycline/hemoglobin solution/carbogen. Finally, the tumor growth delay from fractionated radiation increased from 4.8 days to 13.3 days with TNP-470/minocycline/hemoglobin solution/carbogen. When etanidazole was added to the complete radiation regimen, the tumor growth delay increased further to 20.5 days. These data show that the addition of non-toxic agents that increase tumor oxygenation to cytotoxic therapies can markedly increase therapeutic response.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Gliossarcoma/tratamento farmacológico , Gliossarcoma/radioterapia , Hemoglobinas/uso terapêutico , Animais , Antibióticos Antineoplásicos/farmacologia , Dióxido de Carbono , Carmustina/farmacologia , Bovinos , Terapia Combinada , Cicloexanos , Feminino , Humanos , Minociclina/farmacologia , O-(Cloroacetilcarbamoil)fumagilol , Oxigênio/metabolismo , Radiossensibilizantes , Ratos , Ratos Endogâmicos F344 , Sesquiterpenos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos
20.
J Psychiatr Ment Health Nurs ; 4(4): 275-85, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9362830

RESUMO

Schizophrenia is a devastating illness for the affected individuals and their families. Health care providers and researchers are also challenged by the clinical heterogeneity of this disorder. The goal of the present paper is to offer an updated overview of the aetiology, definition, clinical manifestations and pharmacological and psychosocial treatments of schizophrenia. Finally, some future directions for psychiatric nursing will be suggested in light of the existing knowledge of schizophrenia.


Assuntos
Esquizofrenia/etiologia , Esquizofrenia/terapia , Antipsicóticos/uso terapêutico , Serviços Comunitários de Saúde Mental , Humanos , Enfermagem Psiquiátrica , Psicoterapia , Esquizofrenia/diagnóstico
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