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2.
Gynecol Obstet Fertil Senol ; 49(6): 538-546, 2021 06.
Artigo em Francês | MEDLINE | ID: mdl-33166702

RESUMO

Vulvar carcinomas represent 4% of all gynaecological cancers with 838 new cases in France in 2018. The precursor lesions of vulvar carcinomas are differentiated vulvar intraepithelial lesion (dVIN) in a context of lichen sclerosus and vulvar high-grade squamous intraepithelial lesion (HSIL) link to human papillomavirus (HPV) infection. Three typical clinical forms of HSIL are described: the Bowenoid papulosis, the Bowen's disease and the confluent VIN. Histopathology cannot differentiate effectively these two types of lesions. P16 and P53 immunostaining are valuable tools to respectively assess HPV infection and divide different types of dVIN. However, P53 immunostaining is still lacking sensibility to detect dVIN. First line therapies are medical treatment excluding the cases with a doubt of invasion. The gold standard treatment for dVIN and vulvar HSIL are respectively topical corticosteroids and imiquimod. Primary prevention for vulvar HSIL and dVIN are respectively HPV vaccination and early treatment of lichen sclerosus. Destructive therapy can be used in case of medical treatment failure such as CO2 laser, cryotherapy, dynamic phototherapy. Surgical indications should be carefully assessed between the risk of recurrence, the spread of the lesions, the aesthetic and functional aspect. Surgical procedures consist in either superficial vulvectomy or radical vulvectomy with or without flap reconstruction. Recurrence rate after surgery is around 20%.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Lesões Pré-Cancerosas , Neoplasias Vulvares , Carcinoma in Situ/terapia , Feminino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Neoplasias Vulvares/terapia
3.
Br J Sports Med ; 52(10): 674-677, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-27457796

RESUMO

BACKGROUND AND AIMS: Catastrophic cervical spine injuries are rare in rugby union but require close monitoring. The aim of this study was to analyse the incidence of severe cervical spine injuries and determine the impact of a national prevention programme and new scrum rules implemented by the French Rugby Union. METHODS: A prospective study was performed between 2006 and 2013 including all players affiliated to the French Rugby Union. All cervical spine injuries resulting in death, tetraplegia or a permanent neurological deficit were included. Prevention programmes were implemented from 2007 to 2013 and a change in scrum rules in 2010. To measure the impact of rule changes, results between 2006-2010 and 2010-2013 were compared using a Poisson regression. RESULTS: Altogether, 31 injuries were observed and the mean annual incidence was 1.6 per 100 000 players. There were significantly more injuries in senior players compared to junior players (3.5 vs 0.6 per 100 000 players; CI 95% (2.1 to 4.9) vs (0.1 to 1.0)). Incidence decreased from 1.8 in 2006 to 1.0 per 100 000 players in 2013 (p<0.0001). After 2010, there were significantly fewer injuries during scrums (p=0.02). In contrast, there were significantly more injuries in backs during 2010-2013 compared to 2006-2010 (p=0.003). CONCLUSIONS: The incidence of catastrophic cervical spine injuries has declined in French Rugby Union. The implementation of specific prevention programmes and scrum law changes has notably resulted in a decrease in scrum injuries in forwards. This prospective study should be continued to monitor the future progression of injuries and adapt prevention programmes accordingly.


Assuntos
Traumatismos em Atletas/prevenção & controle , Futebol Americano/lesões , Futebol Americano/normas , Traumatismos da Coluna Vertebral/prevenção & controle , Adolescente , Adulto , Vértebras Cervicais/lesões , França , Humanos , Incidência , Masculino , Estudos Prospectivos , Traumatismos da Coluna Vertebral/etiologia , Adulto Jovem
4.
Ann Chir Plast Esthet ; 61(4): 287-91, 2016 Aug.
Artigo em Francês | MEDLINE | ID: mdl-26169962

RESUMO

The coverage of soft-tissue defects concerning the front of the knee and the proximal lower leg is a complex procedure. The reverse flow anterolateral thigh flap represents a good solution for this defects, especially when the coverage surface is large-sized and a free flap is not appropriate regarding the difficulty of the process. Flap retrograde vascularization is based on the anastomosis between the descending branch of the circumflex femoral artery and lateral superior genicular artery. It is an easy solution with low morbidity. The authors have chosen this flap to cover soft-tissue defect of anterior knee from two patients with total knee prothesis.


Assuntos
Fístula Cutânea/cirurgia , Hematoma/cirurgia , Joelho/cirurgia , Retalhos Cirúrgicos , Idoso , Artroplastia do Joelho/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade
5.
Orthop Traumatol Surg Res ; 101(8): 889-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26563924

RESUMO

INTRODUCTION: Early treatment of initial anterior glenohumeral dislocation in young patients is controversial and the interest of surgery, and notably arthroscopic stabilization, has not been demonstrated. A prospective study was therefore performed to assess (1) short-to-medium-term recurrence rate, (2) functional outcome, and (3) and medium-term osteoarthritis rate. HYPOTHESIS: Early arthroscopic stabilization by anterior capsule-labrum reinsertion after initial anterior shoulder dislocation is associated with low recurrence rate. MATERIALS AND METHODS: Twenty-one patients with initial anterior dislocation were included between June 2002 and February 2004. All patients underwent arthroscopic Bankart repair within 30 days of dislocation. Patients were followed up prospectively, with clinical (Duplay and Constant scores) and radiological assessment (osteoarthritis). RESULTS: There were 5 recurrent dislocations (25%); 2 patients reported sensations of subluxation: i.e., 7 failures (35%). Mean Walch-Duplay score at 10 years was 88±1 (range, 30-100) and mean Rowe score 86±22 (range, 35-100). There was significant internal rotation deficit of one vertebral level between operated and contralateral shoulder (P < 0.005). At 10 years, 3 shoulders (15%) showed Samilson grade 1 centered glenohumeral osteoarthritis. CONCLUSION: Early arthroscopic capsule-labrum reinsertion by the Bankart technique in the month following initial anterior dislocation of the shoulder in patients under 25 years of age provided a low recurrence rate (35%) compared to the literature, including dislocation (25%) and subluxation (10%). Functional outcome was satisfactory, and osteoarthritis rate was low (15% Samilson grade 1). LEVEL OF EVIDENCE: IV, prospective non-comparative study.


Assuntos
Osteoartrite/diagnóstico por imagem , Luxação do Ombro/cirurgia , Adolescente , Adulto , Amputação Cirúrgica , Artroplastia/métodos , Artroscopia/métodos , Feminino , Seguimentos , Humanos , Instabilidade Articular/etiologia , Instabilidade Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite/etiologia , Osteoartrite/cirurgia , Estudos Prospectivos , Radiografia , Recidiva , Rotação , Ombro/cirurgia , Luxação do Ombro/complicações , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Articulação do Ombro/cirurgia , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
6.
Ann Chir Plast Esthet ; 60(6): 465-71, 2015 Dec.
Artigo em Francês | MEDLINE | ID: mdl-26296962

RESUMO

SUBJECT: A recent report from "Agence Nationale de sécurité du medicament et des produits de santé" (ANSM) assesses the rupture of silicone gel breast implants without proposing rules for follow-up and replacement of implants. OBJECTIVE: To demonstrate that systematic follow-up surveillance of silicone breast implants could improve early diagnosis of ruptures; to propose a surveillance protocol based on the findings. MATERIALS AND METHODS: This is a multicentric, retrospective study which reports cases of ruptured silicone gel breast implants from January 2006 to June 2014. Using Case-notes from ANSM and quotations from CCAM certificates, 130cases were gathered from 6 centers. RESULTS: The average time between implantation and the diagnosis of ruptures was 9.24 years (± 6.19). Forty cases of ruptured implants (30.8%) originated from original reconstruction or symmetrisation in the context of a breast carcinoma; and 90 (69.2%) originated from augmentation mammaplasty. The average length in reconstructive group was 6.97 years (± 3.33). The difference in the lifetime of the implants between both groups was statistically significant (P = 0.0291). A clinical abnormality led to an imaging assessment in only 19.7% of cases; rupture was thus mainly discovered incidentally either during a systematic breast screening (59.8%), or during a preoperative examination for an aesthetic surgery (20.5%) (P = 0.0082). CONCLUSIONS: The results suggest that implant ruptures of silicone gel breast implants are under diagnosed. Clinical follow-up seems insufficient to diagnose implant ruptures. Ultra sound surveillance (± MRI) could be proposed 4 years, 7 years and 10 years after the initial surgery. It does not seem appropriate to propose a systematic change of implant without the incidence of a rupture.


Assuntos
Implantes de Mama/efeitos adversos , Falha de Prótese , Feminino , Seguimentos , França/epidemiologia , Humanos , Estudos Retrospectivos , Ruptura Espontânea/epidemiologia , Géis de Silicone
7.
Ann Chir Plast Esthet ; 60(1): 12-8, 2015 Feb.
Artigo em Francês | MEDLINE | ID: mdl-25179862

RESUMO

INTRODUCTION: Photography in plastic surgery is omnipresent. Through its various uses, it may present both ethical and forensic risks. The objective of this study is to analyze the use of medical photography by the plastic surgeon, the perception of this use by the patient, and consequence of such use. METHOD: A questionnaire about the use of medical photography was assessed to 629 plastic surgeons. A questionnaire was given to patients, about their perception of the use of photography by their surgeon. RESULTS: One hundred and seventy-six surgeon's questionnaires and 93 patient's questionnaires were analyzed. For 97.7% of the responding surgeons, the proportion of patients refusing to be photographed was less then 1/20. The objective of the photography was especially medicolegal for 62.5% of the surgeons, especially for following the patient progress (87.5%), partially for the formation (72.1%), partially for scientific publications (57.8%) and not at all for the personal publicity (73.1%). Surgeons often share his photographs with others surgeons (71.1%), sometimes with others medical personnel (48.8%). The security and the access to photographs were determined to be correct for 67.6% of the surgeons and perfect for 23.3%. In total, 17.2% of the surgeons obtained a written consent, 41.4% obtained an oral consent, and 38.5% did not request patient consent. It was found that 48.3% of the surgeons and 40.2% of the patients think that the right to the photographic images belong to the patient. CONCLUSION: Medical photographs expose the plastic surgeon to medico-legal risks. He must know and follow the law in order to prevent eventual legal proceedings.


Assuntos
Fotografação/estatística & dados numéricos , Procedimentos de Cirurgia Plástica , França , Humanos , Consentimento Livre e Esclarecido/legislação & jurisprudência , Consentimento Livre e Esclarecido/estatística & dados numéricos , Participação do Paciente/estatística & dados numéricos , Fotografação/legislação & jurisprudência , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários
8.
Orthop Traumatol Surg Res ; 100(4 Suppl): S261-5, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24709306

RESUMO

The annual incidence of ACL tears is increasing steadily in pediatric patients. Chronic anterior instability causes meniscal lesions at a frequency that increases significantly with the injury-to-surgery interval. Conservative therapy, simple suturing, and isolated extra-articular tendon reconstruction are associated with high failure rates. Intra-articular arthroscopy-assisted tendon reconstruction is a good treatment method, although several different techniques have been described. We used a transphyseal technique with a hamstring tendon graft to treat 14 knees in 13 patients with a mean age of 13 years and 7 months. Mean injury-to-surgery interval was 6 months. Strict compliance with technical rules is required when using this technique. Bone tunnel diameter must not exceed 8 mm. Bone tunnels must be as vertical and central as possible. The fixation material must not bridge the physis (at the femur, cortical fixation; and at the tibia, fixation using a resorbable screw no longer than 25 mm combined with a staple). Meniscal lesions were present in half the knees and meniscal preservation considered mandatory. Conservative treatment of concomitant lesions was performed routinely. After a mean follow-up of 15 months, no recurrent tears or revision procedures for meniscectomy had been recorded. The IKDC grade was A or B in 93% of knees. The mean subjective IKDC score was 83.3 and the Lysholm score was in the excellent or good range in 93% of knees. Of the 14 knees, 2 exhibited signs suggesting femoral epiphysiodesis, with 4° of valgus deformity compared to the contra-lateral knee and no clinical consequences. Transphyseal reconstruction with open physes conducted in strict compliance with technical rules can be performed to control the instability and preserve the menisci. Nevertheless, this technique carries a risk of epiphysiodesis, chiefly at the femur.


Assuntos
Ligamento Cruzado Anterior/cirurgia , Artroscopia/métodos , Procedimentos de Cirurgia Plástica/métodos , Tendões/cirurgia , Tendões/transplante , Adolescente , Feminino , Fêmur/cirurgia , Seguimentos , Lâmina de Crescimento/cirurgia , Humanos , Articulação do Joelho/cirurgia , Masculino , Tíbia/cirurgia , Fatores de Tempo , Resultado do Tratamento
9.
Orthop Traumatol Surg Res ; 98(4 Suppl): S56-65, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22613935

RESUMO

INTRODUCTION: We evaluated the inter- and intra-observer reproducibility of two classification systems for central talar fractures (Hawkins, as modified by Canal and Kelly and then by us; AO/AOT). HYPOTHESIS: The analysis and classification of these fractures will be better with CT scans than with X-rays. MATERIAL AND METHODS: Four observers evaluated 39 X-ray and CT scan files twice in the span of six weeks; each evaluation entailed classifying the fractures and describing their main features. Cohen's Kappa coefficient for inter-rater agreement was calculated and analysed. RESULTS: The inter- and intra-observer reproducibility with CT scans was better with X-rays for most of the parameters evaluated. The modified Hawkins classification provided better reproducibility than the AO/AOT one. However, this classification system was not perfect, even after modifications and use of CT scans. DISCUSSION: CT scans are an essential tool for the analysis of all talar fractures. We modified the Hawkins classification (as modified by Canal and Kelly) to include a Type 0 (no displacement or less than 2mm), include frontal body fractures that are displaced like neck fractures and take into account comminuted fractures and other trauma in the area. LEVEL OF PROOF: IV - retrospective clinical study.


Assuntos
Traumatismos do Tornozelo/classificação , Traumatismos do Tornozelo/diagnóstico por imagem , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico por imagem , Tálus/lesões , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
10.
Orthop Traumatol Surg Res ; 98(4 Suppl): S48-55, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22621831

RESUMO

INTRODUCTION: Displaced talar neck and body fractures are rare and challenging for the surgeon. Results are often disappointing due to inadequate reduction or internal fixation and high rates of osteoarthritis and osteonecrosis. Very few published series describe the long-term results after internal fixation of talar factures. One of the goals of the 2011 SOO meeting symposium was to specifically evaluate the long-term results after internal fixation of talar fractures. This study included only central fractures. MATERIAL AND METHODS: We reviewed the results of 114 central talar fractures that had been treated by internal fixation between 1982 and 2006 in nine hospitals in the Western part of France. The clinical and radiological follow-up was 111 months on average. All the patients with a radiological assessment had at least 5 years of follow-up. RESULTS: Poor reduction was apparent in 33% of cases. The average Kitaoka score was 70/100, which corresponds to an average functional level. At the last follow-up evaluation, 34% of cases had osteonecrosis and 74% had peritalar osteoarthritis. Secondary fusion was required in 25% of cases with an average follow-up of 24 months. DISCUSSION: The complication rate for talar fractures was high, mostly due to osteonecrosis and osteoarthritis; these conditions had an impact on the final outcome. The outcome could be improved by better evaluating these fractures with a CT scan, developing dual surgical approaches to best preserve the bone vascular supply and achieve better reduction, and improving the internal fixation hardware, especially the use of plates for comminuted fractures.


Assuntos
Traumatismos do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Tálus/lesões , Tálus/cirurgia , Adolescente , Adulto , Idoso , Traumatismos do Tornozelo/diagnóstico por imagem , Feminino , Fraturas Ósseas/diagnóstico por imagem , França/epidemiologia , Humanos , Fixadores Internos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/epidemiologia , Radiografia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Tálus/diagnóstico por imagem , Resultado do Tratamento
11.
Orthop Traumatol Surg Res ; 97(2): 111-20, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21439928

RESUMO

INTRODUCTION: To determine six-degree of freedom of total knee arthroplasty kinematics (TKA), optimized matching algorithms for single fluoroscopic image system may be used. Theoretical accuracy of these systems was reported. Nevertheless, all reports were done under idealized laboratory experimental conditions. The aim of this study was to evaluate the "true" accuracy of a flat panel single plane video-fluoroscopy system based on computed-assisted design (CAD) model matching and compare it to TKA kinematics obtained from optoelectronic measurements as gold standard. HYPOTHESIS: The estimation of the error produced by 2D/3D fluoroscopic registration in daily practice is misjudged in most available laboratory reports. MATERIAL AND METHODS: The experimental set-up used a TKA implanted into femoral and tibial cadaver bones. Thirty flexions were simultaneously registered using single plane fluoroscopy and an active optical tracking system. Kinematics registered were compared using the root mean square error (RMS), the concordance correlation coefficient and Bland & Altman plot analysis. RESULTS: The mean range of motion of flexion during the experiment was 106°. The respective RMS for flexion, varus-valgus and internal-external rotation were 0.68, 0.67 and 1.02°. The respective RMS for antero-posterior, medio-lateral and proximo-distal displacement were 1.3, 2.4 and 1.06 mm. Extreme values of the measured error concerning medio-lateral displacement were -5.4 and 22,1mm. DISCUSSIONS: Analysis found some outliners in all degree of freedom with a systematic error and larger standard deviation than already published data. One should make sure that during the experiment the motion of interest is in the in-plane direction. Moreover, this study brings out the true threshold detection of this type of analysis.


Assuntos
Artroplastia do Joelho , Fluoroscopia/métodos , Algoritmos , Fenômenos Biomecânicos , Cadáver , Desenho Assistido por Computador , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Prótese do Joelho , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Amplitude de Movimento Articular , Reprodutibilidade dos Testes
12.
Orthop Traumatol Surg Res ; 96(6): 609-15, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20655819

RESUMO

INTRODUCTION: The use of dual mobility cups is an effective method to prevent dislocations. However, the specific design of these implants can raise the suspicion of increased wear and subsequent periprosthetic osteolysis. HYPOTHESIS: Using radiostereometric analysis (RSA), migration of the femoral head inside the cup of a dual mobility implant can be defined to apprehend polyethylene wear rate. STUDY OBJECTIVES: The study aimed to establish the precision of RSA measurement of femoral head migration in the cup of a dual mobility implant, and its intra- and interobserver variability. MATERIAL AND METHODS: A total hip prosthesis phantom was implanted and placed under weight loading conditions in a simulator. Model-based RSA measurement of implant penetration involved specially machined polyethylene liners with increasing concentric wear (no wear, then 0.25, 0.5 and 0.75mm). Three examiners, blinded to the level of wear, analyzed (10 times) the radiostereometric films of the four liners. There was one experienced, one trained, and one inexperienced examiner. Statistical analysis measured the accuracy, precision, and intra- and interobserver variability by calculating Root Mean Square Error (RMSE), Concordance Correlation Coefficient (CCC), Intra Class correlation Coefficient (ICC), and Bland-Altman plots. RESULTS: Our protocol, that used a simple geometric model rather than the manufacturer's CAD files, showed precision of 0.072mm and accuracy of 0.034mm, comparable with machining tolerances with low variability. Correlation between wear measurement and true value was excellent with a CCC of 0.9772. Intraobserver reproducibility was very good with an ICC of 0.9856, 0.9883 and 0.9842, respectively for examiners 1, 2 and 3. Interobserver reproducibility was excellent with a CCC of 0.9818 between examiners 2 and 1, and 0.9713 between examiners 3 and 1. DISCUSSION: Quantification of wear is indispensable for the surveillance of dual mobility implants. This in vitro study validates our measurement method. Our results, and comparison with other studies using different measurement technologies (RSA, standard radiographs, Martell method) make model-based RSA the reference method for measuring the wear of total hip prostheses in vivo. LEVEL OF EVIDENCE: Level 3. Prospective diagnostic study.


Assuntos
Análise de Falha de Equipamento/métodos , Prótese de Quadril , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Polietileno , Desenho de Prótese , Intensificação de Imagem Radiográfica/métodos , Suporte de Carga/fisiologia , Algoritmos , Fenômenos Biomecânicos , Humanos , Variações Dependentes do Observador , Imagens de Fantasmas , Software , Interface Usuário-Computador
13.
Orthop Traumatol Surg Res ; 96(2): 104-10, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20417907

RESUMO

INTRODUCTION: Five-year following total hip implantation femur adaptive morphology was compared between two groups differing only in their femoral stem design. MATERIAL AND METHODS: Group 1, recruited prospectively, included 51 Dédicace stems(Stryker-Howmedica) and group 2, retrospectively matched to group 1, comprised 51 Kerboull MK3 stems (Stryker-Howmedica). While MK3 prosthetic system increases in size homogeneously (widening along the whole length as the implant dimension increases), the Dédicace prosthetic system provides various metaphyseal widths for a given diaphyseal size. We opted for primary fixation (press fit according to the "French paradox") prior to cementing in both cases, despite the risk of discontinuity in the cement mantle. The homogeneous dimensioning of the MK3 stem enables distal primary fixation, whereas the Dédicace range allows differentiated adaptation to diaphyseal length and metaphyseal caliber. The following parameters were measured and calculated: Noble index, femoral cortical thickness score of Barnett and Nordindiaphyseal filling and stress-shielding at three levels around the stem. RESULTS: Bone-remodeling, assessed on X-ray, was without clinical impact, whether it took the form of spongialization or stress-shielding. The sole factor tending to induce stress-shielding was a high degree of canal filling by the distal third of the stem, more frequently encountered with the MK3 model. Metaphyseal filling was equivalent with all stems. In the matched series on the contralateral healthy side, femoral spongialization was comparable. LEVEL OF PROOF: Level III; case/control study.


Assuntos
Prótese de Quadril , Desenho de Prótese , Adaptação Fisiológica , Idoso , Remodelação Óssea , Cimentação , Feminino , Fêmur/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia
14.
Biopharm Drug Dispos ; 18(9): 779-89, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9429742

RESUMO

Letrozole is a new non-steroidal inhibitor of the aromatase enzyme system. It is currently under development for the treatment of postmenopausal women with advanced breast cancer. Absolute bioavailability of letrozole when given orally as one 2.5 mg film-coated tablet in comparison to the same dose given intravenously as a bolus injection was studied in 12 healthy postmenopausal women. Letrozole absolute systemic bioavailability after p.o. administration was 99.9 +/- 16.3%. Elimination of letrozole was slow. Total-body clearance of letrozole from plasma after i.v. administration was low (2.21 L h-1). The calculated distribution volume at steady state (1.87 L kg-1) suggests a rather high tissue distribution. Biotransformation of letrozole is the main elimination mechanism with the glucuronide conjugate of the secondary alcohol metabolite being the predominant species found in urine. The two study treatments were tolerated equally well.


Assuntos
Inibidores da Aromatase , Inibidores Enzimáticos/farmacocinética , Nitrilas/farmacocinética , Pós-Menopausa/sangue , Triazóis/farmacocinética , Administração Oral , Área Sob a Curva , Disponibilidade Biológica , Biotransformação , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/sangue , Feminino , Humanos , Injeções Intravenosas , Letrozol , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Nitrilas/sangue , Análise de Regressão , Distribuição Tecidual , Triazóis/administração & dosagem , Triazóis/sangue
15.
J Chromatogr B Biomed Appl ; 683(2): 251-8, 1996 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-8891923

RESUMO

An analytical method for the determination of letrozole (CGS 20,267) in plasma and of letrozole and its metabolite, CGP 44,645, in urine is described. Automated liquid-solid extraction of compounds from plasma and urine was performed on disposable 100-mg C8 columns using the ASPEC system. The separation was achieved on an ODS Hypersil C18 column using acetonitrile-phosphate buffer, pH 7, as the mobile phase at a flow-rate of 1.5 ml/min. A fluorescence detector was used for the quantitation. The excitation and emission wavelengths were 230 and 295 nm, respectively. The limits of quantitation (LOQ) of letrozole in plasma and in urine were 1.40 nmol/l (0.4 ng/ml) and 2.80 nmol/l, respectively. The respective mean recoveries and coefficient of variation (C.V.) were 96.5% (9.8%) in plasma and 104% (7.7%) in urine. The LOQ of CGP 44645 in urine was 8.54 nmol/l (2 ng/ml). The mean recovery was 108% (6.3%). The compounds were well separated from co-extracted endogenous components and no interferences were observed at the retention times of compounds. The sensitivity of this method for letrozole in plasma should be sufficient for kinetic studies in humans with single doses of 0.5 mg and possibly less.


Assuntos
Inibidores da Aromatase , Inibidores Enzimáticos/análise , Nitrilas/análise , Triazóis/análise , Aromatase/química , Aromatase/metabolismo , Calibragem , Cromatografia Líquida de Alta Pressão , Ritmo Circadiano , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Jejum , Humanos , Letrozol , Nitrilas/administração & dosagem , Nitrilas/química , Nitrilas/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Triazóis/administração & dosagem , Triazóis/química , Triazóis/metabolismo
16.
J Chromatogr B Biomed Appl ; 678(2): 354-9, 1996 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-8738043

RESUMO

A method for the simultaneous determination of isosorbide dinitrate (ISDN) and its mononitrate metabolites (2- and 5-ISMN) in human plasma by capillary gas chromatography with electron-capture detection was developed. Two internal standards were used: isomannide dinitrate (IMDN) for the determination of ISDN and isomannide mononitrate (IMMN) for the determinations of 2- and 5-ISMN. After addition of the internal standards, the compounds were isolated from plasma by solid-liquid extraction. They were determined by gas chromatography using an electron-capture detector. The reproducibility and accuracy of the method were found suitable in the range of concentrations 2.5-83 ng/ml for ISDN, 2.6-208 ng/ml for 2-ISMN and 2.3-1010 ng/ml for 5-ISMN. The limit of quantitation (LOQ) was about 2.5 ng/ml for each compound. The method was applied to clinical samples.


Assuntos
Cromatografia Gasosa/métodos , Dinitrato de Isossorbida/sangue , Vasodilatadores/sangue , Cromatografia Gasosa/estatística & dados numéricos , Estabilidade de Medicamentos , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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