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杨娅 Thomas Bartel Loredana Latina Guido Caspari 王新房 Raimund Erbel 《华中科技大学学报(医学英德文版)》2002,22(2):158-163
Coronary flow reserve (CFR) has been used toassess coronary microcirculation and epicardial coro-nary stenoses[1— 3 ] . CFR is defined as the ratio ofcoronary flow under maximal coronary vasodilatationto coronary flow under resting conditions[4 ] .Whenthe cross- sectional area of epicardial coronary arteriesis constant,coronary flow velocity (CFV) ratios areequal to volume flow ratios.The most common method used clinically formeasuring CFVR is intracoronary Doppler flow(ICD) analysis re… 相似文献
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Nicola Martinelli Domenico Girelli Paolo Ferraresi Oliviero Olivieri Barbara Lunghi Franco Manzato Roberto Corrocher Francesco Bernardi 《Blood coagulation & fibrinolysis》2007,18(2):125-129
A common factor V gene haplotype, the FVR2 haplotype (FVHR2), has been associated with a reduced cofactor activity in activated protein C-mediated activated factor VIII inactivation. Our aim was to investigate the role of FVHR2 as a possible determinant of factor VIII levels in a population study. A total of 516 individuals (401 men, 115 women; mean age 58.4 +/- 10.8 years) were enrolled within the frame of a regional cardiovascular survey, characterized for factor VIII coagulant activity (FVIII:c) and factor V coagulant activity (FV:c) levels, and genotyped for factor V polymorphisms. In men without signs of overt inflammation, FVHR2 carriers had higher levels of FVIII:c than noncarriers (154 IU/dl, 95% confidence interval = 143-166 versus 142 IU/dl, 95% confidence interval = 138-147; P = 0.045) and were more represented in individuals with high (> or = 150 IU/dl) FVIII:c levels (21.2 versus 10.8%; odds ratio = 2.27, 95% confidence interval = 1.17-4.39 after adjustment for age, blood group and high-sensitivity C-reactive protein levels). In conclusion, this clinical report suggests the common FVHR2 as a possible independent determinant of FVIII:c levels. The report concomitantly addresses the relationship between factor V and factor VIII levels and supports the hypothesis of a mild prothrombotic role of FVHR2 by means of increased factor VIII levels. 相似文献
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Carlo Aprile Raffaella Saponaro Giuseppe Villa Mauro Carena Fabio Lunghi Sebastiano B. Solerte Alessandro Salvadeo 《European journal of nuclear medicine and molecular imaging》1986,12(1):37-40
The aim of this work is to correlate the net kidney uptake of99mTc-aprotinin (TcA) in 103 subjects with separate effective renal plasma flow (ERPF) and some blood chemistry parameters at 90, 180, and 360 min postinjection both in the normal and diseased kidney. Correlations found with separate ERPFs are highly significant at any time (P < 0.001). However, although the slope of the regression line is steeper at 180 min,r tends to deteriorate slightly with time postinjection and a higher intercept on they axis: this pattern is more pronounced if diseased kidneys are considered separately. The following are probably related to the renal handling of TcA: (1) Early scans better reflect blood flow to the kidney, while later scans are more related to the metabolism/excretion tubular mechanisms; (2) correlations found with urea, creatinine, urea clearance, and creatinine clearance are highly significant at any time; (3) in 20 additional patients with diseased kidneys, renal uptake measurements done 360 min postinjection first with TcA and then with DMSA showed better correlations with ERPF employing TcA. Our results indicate that TcA is a feasible indicator of split renal function even at 90 min postinjection when a scan is easily carried out on an outpatient basis.This paper was in part presented at the European Nuclear Medicine Congress, August 14–17, 1984, Helsinki, Finland 相似文献
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Franco Di Filippo M.D. Anna Maria Calabrò M.D. Andrea Cavallari M.D. Sandro Carlini M.D. Giovanni Luca Buttini M.D. Francesco Moscarelli M.D. Francesco Cavaliere M.D. Loredana Piarulli M.D. Renato Cavaliere M.D. 《World journal of surgery》1988,12(3):332-339
Eighty-six patients with locally advanced, high-grade soft tissue sarcomas of the extremities were studied prospectively in order to determine the efficacy of hyperthermic perfusion (HP) or hyperthermic antiblastic perfusion (HAP) as the first step of a combined multimodality therapy.
The immediate response was evaluated in terms of tumor regression, and results confirmed the in vivo sensitivity of human sarcomas to the selective antineoplastic action of heat alone or combined with drugs (melphalan, actinomycin D, and cis-platinum). HAP has been shown to be simpler and safer than HP, and it is now currently routinely employed.
As far as the long-term cure is concerned, all the patients have been evaluated for functional results, locoregional control, and survival, according to the different treatment schedules.
The first clinical trials employed HP or HAP followed by delayed surgery alone. In 11 of 17 evaluable patients treated with HP, and in 17 of 29 treated with HAP, conservative surgery could be performed. A high incidence of locoregional relapse (24%) occurred, with low overall survival rates: 50.1% and 31.7% at 5 and 10 years after HP plus surgery, and 47.9% after HAP plus surgery at both 5 and 10 years.
The protocol was, therefore, modified to include continuous intraarterial infusion of Adriamycin® (ADR) (17 patients) or radiotherapy (9 patients) before surgery.
The results obtained thus far may be summarized as follows: (a) conservative surgery with functional limb-salvage was possible in all patients; (b) the percentage of locoregional failure decreased to approximately 12% after HAP + ADR infusion + excision, the 5- and 10-year overall survival rates both being 77.6 %, and the 5- and 10-year disease-free rates both being 57.8%; (c) no local recurrences occurred in the group treated with HAP + radiotherapy + excision with a 5-year overall survival rate of 71.5% and a 5-year disease-free rate of 50.4%.
In conclusion, the combined multimodality approaches employed appear to have improved both functional results and long-term cure, even though these must be further confirmed on a larger series of patients.
Supported by Special Project Hyperthermia from the Italian Ministry of Health. 相似文献
Resumen Ochenta y seis pacientes con sarcomas de los tejidos blandos de las extremidades, de alto grado histológico, e invasión local avanzada fueron estudiados en forma prospectiva con el objeto de determinar la eficacia de la perfusión hipertérmica (PH) o la perfusión hipertérmica antiblástica (PHA) como primer paso dentro de una terapia combinada multimodal.La respuesta inmediata fue valorada en términos de la regresión tumoral, y los resultados confirmaron la sensibilidad in vivo de los sarcomas humanos a la acción antineoplásica selectiva del calor sólo o combinado con drogas (melfalán, actinomicina D, y cis-platino). La PHA ha demostrado ser más sencilla y más segura que la PH y actualmente es utilizada en forma rutinaria.En lo referente a curación a largo plazo, todos los pacientes han sido evaluados en cuanto a resultados funcionales, control locorregional, y supervivencia, de acuerdo a los diferentes programas terapéuticos.En los primeros ensayos clínicos se utilizó PH o PHA seguida de cirugía solamente. En 11 de 17 pacientes valorables tratados con PH y 17 con PHA, fue posible realizar cirugía conservadora. Se presentó una incidencia alta de relapso locorregional (24%), con tasas bajas de supervivencia global: 50.1% y 31.7% a 5 y 10 años con PH y cirugía, y 47.9% con PHA y cirugía tanto a 5 como a 10 años.El protocolo fue consecuentemente modificado para incluir una infusión intraarterial continua de Adriamicina® (ADR) (17 pacientes) o radioterapia (9 pacientes) antes de la cirugía.Los resultados logrados hasta el momento pueden ser resumidos así: (a) la cirugía conservadora con salvamento del miembro fue posible en la totalidad de los pacientes; (b) el porcentaje de falla locorregional disminuyó aproximadamente 12% después de PHA + infusión de ADR + resección, con supervivencias globales a 5 y 10 años de 77.6%, y tasas de estado libre de enfermedad a 5 y 10 años de 57.8%; (c) no se presentaron recurrencias locales en el grupo tratado con PHA + radioterapia + resección, con una tasa de supervivencia global a 5 años de 71.5% y una tasa de estado libre de enfermedad a 5 años de 50.4%.En conclusión, los aproches con terapia combinada multimodal empleados parecen haber mejorado tanto los resultados funcionales como las tasas de curación a largo plazo, aunque estos resultados aún deben ser reconfirmados en una serie mayor de pacientes.
Résumé Une étude prospective concernant 86 malades qui présentaient un sarcome des parties molles des membres de stade évolutif avancé a été entreprise pour déterminer l'efficacité de la perfusion hyperthermique ou de la perfusion hyperthermique antiblastique en tant que première étape d'un traitement à modalités multiples.La réponse immédiate a été appréciée en fonction de la régression tumorale. Les résultats ont confirmé la sensibilité in vivo des sarcomes humains à l'action antinéoplasique sélective de la chaleur employée isolemment ou combinée avec des drogues (melphalan, actinomycine D, et cis-platinum). La perfusion hyperthermique antiblastique s'est montrée plus simple et plus sûre que la perfusion hyperthermique, et de ce fait est devenue une méthode thérapeutique normalement employée.Pour apprécier l'action thérapeutique à long terme tous les malades ont été étudiés en tenant compte des résultats fonctionnels, du contrôle loco-régional, et de la survie obtenus selon les différentes thérapeutiques appliquées.Les premiers essais ont eu recours à l'hyperthermie thermique ou à l'hyperthermie thermique antiblastique suivie d'une intervention chirurgicale. Chez 11 des 17 malades traités par l'hyperthermie thermique, et chez 17 des 29 malades soumis à l'hyperthermie antiblastique le traitement chirurgical conservateur a pu être réalisé. Les résultats furent les suivants: fréquence importante des récidives loco-régionales (24%); taux global de survie bas: 50.1% et 31.7% à 5 ans et 10 ans après perfusion hyperthermique suivie de chirurgie, ce taux étant de 47.9% après perfusion hyperthermique antiblastique suivie de chirurgie à 5 ans et 10 ans.En fonction de ces résultats le protocole thérapeutique fut modifié en y ajoutant une transfusion intra-artérielle continue d'Adriamycine® (17 malades) ou de la radiothérapie (9 malades) avant l'intervention.Les résultats obtenus à ce jour peuvent se résumer ainsi: (a) la chirurgie conservatrice permettant de sauver un membre fonctionnel est toujours possible; (b) la poucentage d'échec régional décroit environ jusqu' à 12% après perfusion hyperthermique antiblastique associée à la perfusion d'Adriamycine® et l'excision, le taux global de survie à 5 ans et 10 ans étant de 77.6%, le taux d'absence de la maladie à 5 ans et 10 ans étant de 57.8%; (c) aucune récidive locale n'est survenue dans le groupe traité par perfusion hyperthermique antiblastique associé à la radiothérapie et à l'exérèse, le taux global de survie à 5 ans étant de 71.5% et le taux d'absence de la maladie à 5 ans étant de 50.4%.En conclusion le traitement qui a été employé associant plusieurs modalités thérapeutiques a entrainé une amélioration des résultats fonctionnels et de la cure à long terme encore que ce fait demande a été confirmé par une étude étendue à un plus grand mombre de malades.
Supported by Special Project Hyperthermia from the Italian Ministry of Health. 相似文献
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Franca Formelli Loredana Cleris Roberto Carsana 《Cancer chemotherapy and pharmacology》1988,21(4):329-336
Summary The effect of the combined administration of verapamil (i.p. twice daily) and doxorubicin (i.v once weekly) was tested in mice bearing the following: (a) a tumor with induced resistance to doxorubicin (B16VDXR melanoma line); (b) a tumor inherently resistant (MXT mammary carcinoma); and (c) four solid tumors sensitive to doxorubicin (B16 melanoma, B16V melanoma line, M5076 reticulum cell sarcoma, and Lewis lung carcinoma). Verapamil, given according to this treatment schedule, reached peak plasma concentrations of 3 M. Such treatment did not enhance doxorubicin activity on either inherently or induced resistant tumors, whereas it significantly enhanced doxorubicin growth inhibition in all the sensitive tumors except the Lewis lung carcinoma. Doxorubicin pharmacokinetics after administration of the drug alone and in combination with verapamil was analyzed after the first and repeated treatments in animals bearing B16 melanoma or its resistant subline B16VDXR. The resistance of the B16VDXR line was associated with the ability of the tumor to retain less doxorubicin (AUC=83 g h/g) than the sensitive tumor B16 (AUC=204 g h/g) in spite of similar initial levels. The potentiating effect of doxorubicin activity by, verapamil in B16 melanoma was not associated with increased doxorubicin levels or retention in the tumor, nor were differences in doxorubicin levels or retention found in the B16VDXR line. The combined treatment did not modify doxorubicin pharmacokinetics in plasma, heart, or spleen. These studies suggest that verapamil in vivo is ineffective in potentiating doxorubicin activity in tumors against which doxorubicin is inactive, that sensitive tumors are heterogeneous in their sensitivity to modulation by verapamil, and that this effect is not associated with modification of doxorubicin pharmacokinetics.This work was supported by grant no. 84.00855.44 of the Finalized Project Oncologia from the Consiglio Nazionale delle Ricerche, Rome 相似文献
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Farilla L Tiberti C Luzzago A Yu L Eisenbarth GS Cortese R Dotta F Di Mario U 《European journal of immunology》2002,32(5):1420-1427
Autoantigenic epitope mapping represents a critical issue in autoimmune diseases. The islet tyrosine phosphatase-like protein IA-2/ICA512bdc is a major autoantigen in type 1 diabetes (IDDM), but the epitopes responsible for autoantibody binding have been only partially defined. The aim of our study was to identify ICA512bdc epitopes, and in particular mini-epitopes, utilizing a novel strategy for autoimmune diseases. The study was performed in three sequential steps: (1) construction of a lambda-phage surface-displayed ICA512bdc cDNA library with the methodology of tagged random priming with peptides displayed as a fusion to the C terminus of the capsid protein D; (2) affinity selection of the resulting library, followed by immunoscreening, enzyme-linked immunosorbent assay and sequence analysis of positive clones, and (3) radioimmunoprecipitation to detect autoantibodies to the selected clones. This strategy resulted in the identification of two epitopes (IA-2 residues 761 - 964 and 929 - 979), which were recognized by 100 % and 62.9 % ICA512bdc-positive IDDM patients, respectively. Interestingly, the larger clone was detected also by a proportion (16.7 %) of new onset ICA512bdc-negative patients, thus suggesting that this region contains not only the main autoantigenic repertoire of ICA512bdc molecule, but is able to detect IA-2 autoantibodies in even higher percentages of patients. In addition, this study showed the existence of multiple epitopes located in the C-terminal domain of the IA-2 protein, one of which is formed by the 50 C-terminal amino acids, and provided evidence that the strategy used represents a valid tool for identification of epitopes within autoantigenic molecules. 相似文献
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