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1.
Breast Cancer Res Treat ; 199(2): 265-279, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37010651

ABSTRACT

PURPOSE: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. METHODS: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb-July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. RESULTS: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32-81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7-8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months' treatment duration; median of 4 mm [IQR - 20, 4]. In a small subset of patients (n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month's duration of BrET. DISCUSSION: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials.


Subject(s)
Breast Neoplasms , COVID-19 , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Pandemics , Ki-67 Antigen/metabolism , Cohort Studies , Prognosis , Neoadjuvant Therapy
2.
Colorectal Dis ; 23(10): 2723-2730, 2021 10.
Article in English | MEDLINE | ID: mdl-34314565

ABSTRACT

AIM: The aim was to determine the accuracy of C-reactive protein (CRP), procalcitonin and neutrophils in the early detection (fourth postoperative day) of anastomotic leakage (AL) after colorectal surgery. METHODS: We conducted a multicentre, prospective study that included a consecutive series of patients who underwent colorectal resection with anastomosis without ostomy (September 2015 to December 2017). CRP, procalcitonin and neutrophil values on the fourth postoperative day after colorectal resection along with the postoperative outcome (60-day AL, morbidity and mortality) were prospectively included in an online, anonymous database. RESULTS: The analysis ultimately included 2501 cases. The overall morbidity and mortality was 30.1% and 1.6%, respectively, and the AL rate was 8.6%. The area under the receiver operating characteristic curve values (95% CI) for detecting AL were 0.84 (0.81-0.87), 0.75 (0.72-0.79) and 0.70 (0.66-0.74) for CRP, procalcitonin and neutrophils, respectively. The best cut-off level for CRP was 119 mg/l, resulting in 70% sensitivity, 81% specificity and 97% negative predictive value. After laparoscopic resection, the accuracy for CRP and procalcitonin was increased, compared with open resection. The combination of two or three of these biomarkers did not significantly increase their accuracy. CONCLUSION: On the fourth postoperative day, CRP was the most reliable marker for excluding AL. Its high negative predictive value, especially after laparoscopic resection, allows for safe hospital discharge on the fourth postoperative day. The routine use of procalcitonin or neutrophil counts does not seem to increase the diagnostic accuracy.


Subject(s)
Colorectal Neoplasms , Procalcitonin , Anastomotic Leak/diagnosis , Anastomotic Leak/etiology , Biomarkers , C-Reactive Protein/analysis , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Humans , Neutrophils/chemistry , Prospective Studies , ROC Curve
4.
Rev. senol. patol. mamar. (Ed. impr.) ; 33(2): 61-67, abr.-jun. 2020.
Article in English | IBECS | ID: ibc-188000

ABSTRACT

We are facing a pandemic that is going to affect a significant part of the population. At the end of April in the world there are about 3,000,000 cases, with 205,000 deaths and 860,000 patients recovered. The response to this pandemic has in many cases led to a significant change in the daily work of caring for cancer patients, the good results of which depend largely on time-adjusted protocols and multidisciplinary treatments. We present a review of local, surgical and radiotherapy treatment together with authors' recommendations made from personal experience on ways to act in the diagnosis and surgical treatment of breast cancer during the COVID-19 pandemic. The multidisciplinary Breast Committees must continue to meet weekly in videoconference format. All surgical actions and irradiations must be carried out with maximum safety for both the patients and the participating teams. Hypofractionation in radiation therapy should be the standard treatment. Sometimes it is recommended to apply a primary systemic treatment or even a primary irradiation. Great coordination between the surgical and oncology teams, both medical and radiotherapeutic, is essential


Nos enfrentamos a una pandemia que afecta a una parte importante de la población.  A finales de abril de 2020, en el mundo hay cerca de 3.000.000 de casos, con 205.000 muertes y 860.000 pacientes recuperados. La respuesta a esta pandemia en muchos casos ha supuesto modificaciones importantes en el cuidado diario de las pacientes con cáncer, dependiendo el buen resultado en buena parte del ajuste de los protocolos a las circunstancias especiales y a los tratamientos multidisciplinarios. Presentamos una revisión del tratamiento quirúrgico y radioterapia junto con las recomendaciones de los autores basadas en su experiencia personal a la hora del diagnóstico y tratamiento locorregional del cáncer de mama durante la pandemia del COVID-19. Los comités multidisciplinarios deben seguir reuniéndose semanalmente en formato de videoconferencia. Todos las intervenciones quirúrgicas e irradiaciones deben ser llevadas a cabo con la máxima seguridad tanto para las pacientes como para el personal sanitario que participa. El hipofraccionamiento debe ser el tratamiento radioterápico estándar. En algunos casos se utilizará tratamiento sistémico primario o incluso radioterapa preoperatoria. Es esencial una coordinación importante entre los equipos quirúrgicos y los oncológicos, tanto radioterápicos como médicos


Subject(s)
Humans , Female , Breast Neoplasms/therapy , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/prevention & control , Pandemics , Severe acute respiratory syndrome-related coronavirus/pathogenicity , Universal Precautions/methods , Patient Safety/standards , Remote Consultation/methods , Telemonitoring , Patient Care Team/organization & administration , Breast Neoplasms/diagnosis , Delayed Diagnosis/prevention & control , Time-to-Treatment/trends
6.
Rev. senol. patol. mamar. (Ed. impr.) ; 32(2): 61-66, abr.-jun. 2019. graf
Article in Spanish | IBECS | ID: ibc-187037

ABSTRACT

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Estos artículos presentan un consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) con la idea de unificar, en esta primera parte, los criterios de diagnóstico de esta enfermedad describiendo asimismo la epidemiología y la etiopatogenia


Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin lymphoma that has been described in the context of reconstructive and aesthetic breast implant surgery. These articles present a consensus of the Spanish Society of Senology and Breast Disease (SESPM). In this first part, the aim is to unify the diagnostic criteria of this disease and describe its epidemiology and etiopathogenesis


Subject(s)
Humans , Female , Lymphoma, Large-Cell, Anaplastic/diagnosis , Breast Implants/adverse effects , Breast Neoplasms/pathology , Mammography/statistics & numerical data , Prostheses and Implants/adverse effects , Consensus , Breast Neoplasms/epidemiology , Lymphoma, Large-Cell, Anaplastic/epidemiology , Neoplasms, Second Primary/pathology , Lymphoma, Large-Cell, Anaplastic/pathology , Biopsy/methods , Practice Patterns, Physicians'
7.
Rev. senol. patol. mamar. (Ed. impr.) ; 32(2): 67-74, abr.-jun. 2019. tab, graf
Article in Spanish | IBECS | ID: ibc-187038

ABSTRACT

El linfoma anaplásico de células grandes asociado a implantes mamarios (BIA-ALCL según sus siglas en inglés) es un tipo raro de linfoma no Hodgkin que se ha descrito en el contexto de la cirugía reconstructiva y estética de mama mediante implantes. Este segundo artículo presenta la parte del consenso de la Sociedad Española de Senología y Patología Mamaria (SESPM) sobre el tratamiento quirúrgico, médico, radioterápico, pronóstico y seguimiento


Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare type of non-Hodgkin lymphoma that has been described in the context of breast implant reconstructive and cosmetic surgery. This second article presents the consensus of the Spanish Society of Senology and Breast Disease (SESPM) on the medical and surgical treatment of this disease, radiotherapy, prognosis and follow-up


Subject(s)
Humans , Female , Lymphoma, Large-Cell, Anaplastic/therapy , Breast Implants/adverse effects , Breast Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Radiotherapy/methods , Prostheses and Implants/adverse effects , Consensus , Breast Neoplasms/pathology , Lymphoma, Large-Cell, Anaplastic/pathology , Neoplasms, Second Primary/pathology , Practice Patterns, Physicians' , Neoplasm Staging/methods , Prognosis
8.
Int. j. morphol ; 37(1): 232-236, 2019. tab, graf
Article in English | LILACS | ID: biblio-990032

ABSTRACT

SUMMARY: The nasolabial region is the central esthetic unit of the face and is considered one of the most important determinants of the facial esthetic. The facial morphometry of soft tissues is a very important tool in facial surgery. Advances have been made recently in the capture and analysis of 3D images, which offer great development potential in the diagnosis and treatment of facial deformities. The aim of this study was to characterize the nasolabial region of patient candidates for orthognathic surgery using 3D facial captures. A study was conducted to characterize the width of the nasal base and the nasolabial angle in adult patients through 3D photographs. 30 subjects were included, taking two 3D photos each, one in a resting position and the other smiling. The three-dimensional capture was done with the 3dMDface System. The measurements were taken with the 3dMD Vultus software. The length of the alar base was an average of 34.3 ± 2.6 mm at rest, and 39.1 ± 2.9 mm smiling. The mean of the nasolabial angle was 104.6 ± 9.6° at rest and 105.4 ± 14.3º smiling. Additionally, the distance of the alar base smiling compared to its distance at rest increased an average of 4.83 mm, whereas the nasolabial angle smiling increased an average of 0.8º compared to at rest. In this study, the nasolabial angle did not present any significant changes so that its assessments in the case of facial modifications can be standard; the width of the nasal base is significantly modified with the smile and thus a more intense study of any type of modification in this area is required.


RESUMEN: La región nasolabial es la unidad estética central de la cara y se considera uno de los determinantes más importantes de la estética facial. La morfometría facial en tejidos bandos, es una herramienta de gran importancia en Cirugía Facial. En el último tiempo, se han realizado avances en captura y análisis de imágenes 3D, las cuales ofrecen un gran potencial de desarrollo en el diagnóstico y tratamiento de las deformidades faciales. El objetivo de éste trabajo fue caracterizar mediante capturas faciales 3D la región nasolabial de pacientes candidatos a cirugía ortognática. Se realizó un estudio para caracterizar a través de fotografías tridimensionales de pacientes adultos el ancho de la base nasal y el ángulo nasolabial. Se incluyeron 30 sujetos, tomando 2 fotografías 3D a cada uno, una en posición de reposo y otra en sonrisa. Se realizó la captura tridimensional con la camara facial 3dMDface System. Las mediciones fueron realizadas con el software 3dMD Vultus. La longitud de base alar en reposo, fue en promedio de 34,3 ± 2,6 mm, y de 39,1 ± 2,9 mm, en sonrisa. Por otra parte, la media del ángulo nasolabial en reposo fue de 104,6 ± 9,6° y en sonrisa, de 105,4 ± 14,3º. Por otro lado, la distancia de la base alar en sonrisa respecto a su distancia en reposo, aumentó un promedio de 4,83 mm, mientras que el ángulo nasolabial en sonrisa, aumentó en promedio 0,8º respecto a la posición de reposo. En esta investigación, el ángulo nasolabial no presentó cambios significativos de forma que su valoración frente a modificaciones faciales puede ser estándar; el ancho de base nasal se modifica significativamente con la sonrisa de forma que su estudio debe ser más agudo frente a cualquier tipo de modificación en esta zona.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Photogrammetry/methods , Nose/diagnostic imaging , Imaging, Three-Dimensional/methods , Lip/diagnostic imaging , Smiling , Image Processing, Computer-Assisted , Nose/anatomy & histology , Lip/anatomy & histology
9.
Rev Esp Enferm Dig ; 107(9): 570-2, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26334466

ABSTRACT

Intestinal anisakiasis is a rare parasitic disease and difficult to diagnose due to symptoms are not specific, so it is considered an underdiagnosed disease. The clinical suspicion with a correct diagnosis of anisakiasis allows the establishment of a correct treatment; in most cases, the resolution is possible with conservative treatment, avoiding unnecessary surgery to the preoperative differential diagnosis of acute abdomen. We report the case of apatient who required urgent surgery secondary to an exacerbation of chronic anisakiasis.


Subject(s)
Anisakiasis/complications , Ileal Neoplasms/etiology , Ileal Neoplasms/pathology , Mesentery/pathology , Anisakiasis/diagnostic imaging , Chronic Disease , Humans , Ileal Neoplasms/surgery , Male , Mesentery/diagnostic imaging , Middle Aged , Tomography, X-Ray Computed
10.
Rev. esp. enferm. dig ; 107(9): 570-572, sept. 2015.
Article in Spanish | IBECS | ID: ibc-140756

ABSTRACT

La anisakiasis intestinal es una enfermedad parasitaria rara y de difícil diagnóstico, ya que las manifestaciones clínicas son inespecíficas, por lo que se considera una enfermedad infradiagnosticada. La sospecha clínica junto a un correcto diagnóstico de la anisakiasis permite la instauración de un tratamiento correcto, ya que en la mayoría de los casos es posible la resolución del cuadro con tratamiento conservador, evitando cirugías innecesarias ante el diagnóstico diferencial preoperatorio de abdomen agudo. Presentamos el caso clínico de un paciente que precisó una intervención quirúrgica urgente secundaria a una reagudización de anisakiasis crónica


Intestinal anisakiasis is a rare parasitic disease and difficult to diagnose due to symptoms are not specific, so it is considered an underdiagnosed disease. The clinical suspicion with a correct diagnosis of anisakiasis allows the establishment of a correct treatment; in most cases, the resolution is possible with conservative treatment, avoiding unnecessary surgery to the preoperative differential diagnosis of acute abdomen. We report the case of a patient who required urgent surgery secondary to an exacerbation of chronic anisakiasis


Subject(s)
Humans , Male , Anisakiasis/complications , Anisakiasis/diagnosis , Anisakiasis/drug therapy , Diagnosis, Differential , Abdomen, Acute/complications , Abdomen, Acute/surgery , Mesentery/pathology , Mesentery/surgery , Mesentery , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms
11.
Rev. esp. patol ; 47(1): 22-32, ene.-mar. 2014. tab
Article in Spanish | IBECS | ID: ibc-119948

ABSTRACT

La biopsia selectiva del ganglio centinela es una técnica diagnóstica aceptada como el procedimiento de elección para la estadificación axilar del cáncer de mama. En este documento, correspondiente a la última Reunión de Consenso celebrada en Valencia y organizada por la Sociedad Española de Senología y Patología Mamaria, se actualizan los consensos previos y se reflejan las conclusiones acerca de las últimas propuestas en el manejo del ganglio centinela en el cáncer de mama (AU)


Sentinel lymph node biopsy is currently a widely accepted diagnostic technique and is the procedure of choice for axillary staging of breast cancer. In this article, following the latest Consensus Meeting held in Valencia organized by the Spanish Society of Senology and Breast Pathology, previous consensus are updated. Also discussed are conclusions related to the latest trends in the management of the sentinel node in breast cancer (AU)


Subject(s)
Humans , Female , Sentinel Lymph Node Biopsy/methods , Breast Neoplasms/pathology , Pathology, Molecular/methods , Tumor Burden , Lymph Node Excision/methods , Patient Selection , Neoplasm Staging
12.
Rev. senol. patol. mamar. (Ed. impr.) ; 27(1): 43-53, ene.-mar. 2014.
Article in Spanish | IBECS | ID: ibc-118566

ABSTRACT

La biopsia selectiva del ganglio centinela es una técnica diagnóstica aceptada como el procedimiento de elección para la estadificación axilar del cáncer de mama. En este documento, correspondiente a la última Reunión de Consenso celebrada en Valencia y organizada por la Sociedad Española de Senología y Patología Mamaria, se actualizan los consensos previos y se reflejan las conclusiones acerca de las últimas propuestas en el manejo del ganglio centinela en el cáncer de mama


Sentinel lymph node biopsy is currently a widely accepted diagnostic technique and is the procedure of choice for axillary staging of breast cancer. In this article, following the latest Consensus Meeting held in Valencia organized by the Spanish Society of Senology and Breast Pathology, previous consensus are updated. Also discussed are conclusions related to the latest trends in the management of the sentinel node in breast cancer


Subject(s)
Humans , Female , Sentinel Lymph Node Biopsy/instrumentation , Sentinel Lymph Node Biopsy/methods , Sentinel Lymph Node Biopsy , Breast Neoplasms/diagnosis , Molecular Biology/methods , Lymph Node Excision/instrumentation , Lymph Node Excision/methods , Lymph Node Excision , Sentinel Lymph Node Biopsy/standards , Sentinel Lymph Node Biopsy/trends , Societies, Medical/standards , Societies, Medical , Brachytherapy/instrumentation , Brachytherapy/methods , Radiotherapy/instrumentation , Radiotherapy/methods
13.
Cir. Esp. (Ed. impr.) ; 91(5): 287-293, mayo 2013. tab
Article in Spanish | IBECS | ID: ibc-112336

ABSTRACT

INTRODUCCIÓN: Los testigos de Jehová rechazan la transfusión sanguínea. El conflicto aparece cuando el enfermo, afiliado a la sanidad pública, acude a centros de cirugía sin sangre, para después reclamar los gastos creados. OBJETIVOS: Análisis de reclamaciones jurídicas de reintegro de gastos en enfermos testigos de Jehová tratados fuera del sistema de salud pública. Comparación de costes, respecto a costes mediante Grupo de Diagnóstico Relacionado (GRD) en un modelo hipotético de asistencia similar e igual estancia en nuestro hospital. MATERIAL Y MÉTODOS: Estudio retrospectivo de sentencias de tribunales Superior de Justicia, Supremo y Constitucional. Análisis económico: utilizamos información clínica obtenida en la sentencia, para procesarlo en GRD, de nuestro hospital con 3MHealth Information Systems. Resultado/conclusiones: El Estado no tiene el deber de financiar aspectos religiosos o ajenos al interés general. El establecimiento de protocolos de actuación evitaría conflictos éticos. Diferencias difícilmente justificables en costes solicitados, 431.001,66 €, y en relación a un modelo con igual estancia, 397.404,48 €


INTRODUCTION: Jehovah's witnesses refuse blood transfusions. The conflict arises when the patient, entitled to public health treatment, come to surgical centres without blood, to later claim the costs incurred. OBJECTIVES: To analyse the legal claims for the refunding of costs by Jehovah's witnesses treated outside the public health system. To make a cost comparison regarding this, using Diagnosis Related Groups (DRGs) in a similar hypothetical healthcare model and equal to a stay in our hospital. MATERIAL AND METHODS: A retrospective study was made of the High, Constitutional, and Supreme Court rulings. A cost analysis was made using the clinical information obtained in the rulings, to process this in the DRG in our hospital using 3MHealth Information Systems. Results/CONCLUSIONS: The State is not obliged to finance religious aspects or those outside the general interest. The establishment of working protocols would avoid ethical conflicts. There are very difficult to justify differences in the costs demanded, 431,001.66 €, and compared to a model with an equal stay, 397,404.48 €


Subject(s)
Humans , /statistics & numerical data , Insurance Claim Review , /economics , Jehovah's Witnesses , Religion and Medicine , Retrospective Studies , Practice Patterns, Physicians'/legislation & jurisprudence
14.
Cir Esp ; 91(5): 287-93, 2013 May.
Article in Spanish | MEDLINE | ID: mdl-22498304

ABSTRACT

INTRODUCTION: Jehovah's witnesses refuse blood transfusions. The conflict arises when the patient, entitled to public health treatment, come to surgical centres without blood, to later claim the costs incurred. OBJECTIVES: To analyse the legal claims for the refunding of costs by Jehovah's witnesses treated outside the public health system. To make a cost comparison regarding this, using Diagnosis Related Groups (DRGs) in a similar hypothetical healthcare model and equal to a stay in our hospital. MATERIAL AND METHODS: A retrospective study was made of the High, Constitutional, and Supreme Court rulings. A cost analysis was made using the clinical information obtained in the rulings, to process this in the DRG in our hospital using 3MHealth Information Systems. RESULTS/CONCLUSIONS: The State is not obliged to finance religious aspects or those outside the general interest. The establishment of working protocols would avoid ethical conflicts. There are very difficult to justify differences in the costs demanded, 431,001.66 €, and compared to a model with an equal stay, 397,404.48 €.


Subject(s)
Jehovah's Witnesses , Public Health , Reimbursement Mechanisms , Surgical Procedures, Operative/economics , Humans , Retrospective Studies
15.
Drug Metab Pharmacokinet ; 27(6): 605-13, 2012.
Article in English | MEDLINE | ID: mdl-22673010

ABSTRACT

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6, and is also a potent mechanism-based inhibitor of the enzyme. After assessing the inhibition and recovery of CYP2D6 in a previous study, the aim of this work was to study in humans the activity of CYP1A2 in vivo after CYP2D6 had been inhibited by MDMA, using caffeine as a probe drug. Twelve male and nine female recreational MDMA users were included. In session 1, 100 mg of caffeine was given at 0 h. In session 2, a 1.5 mg/kg MDMA dose (range 75-100 mg) was given at 0 h followed by a 100 mg dose of caffeine 4 h later. Aliquots of plasma were assayed for caffeine (137X) and paraxanthine (17X) and statistically significant differences were assessed with a one-way ANOVA. There were significant gender differences at basal condition, which persisted after MDMA administration. CYP1A2 activity was higher in both genders after drug administration, with an increase in 40% in females and 20% in males. Results show an increase in CYP1A2 activity when CYP2D6 is inhibited by MDMA in both genders, being more pronounced in females.


Subject(s)
Caffeine/administration & dosage , Cytochrome P-450 CYP1A2/metabolism , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Adult , Area Under Curve , Caffeine/blood , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP2D6 Inhibitors , Female , Half-Life , Humans , Male , Sex Factors , Theophylline/administration & dosage , Theophylline/blood
17.
Clin Pharmacokinet ; 50(5): 319-29, 2011 May.
Article in English | MEDLINE | ID: mdl-21456632

ABSTRACT

BACKGROUND AND OBJECTIVE: 3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is a ring-substituted amphetamine widely used for recreational purposes. MDMA is predominantly O-demethylenated in humans by cytochrome P450 (CYP) 2D6 and is also a potent mechanism-based inhibitor of the enzyme. This study assessed the inhibition and recovery half-life of CYP2D6 and CYP3A4 activity in female subjects by administering the probe drug dextromethorphan before and repeatedly after MDMA administration. These data were compared with the data obtained from a previous study in male subjects. STUDY DESIGN: Twelve healthy female subjects who were CYP2D6 extensive metabolizers participated as outpatients in two experimental sessions. Session 1 was conducted over 2 days and session 2 over 10 days, with a minimum of 3 days between sessions. In session 1, subjects received a single oral dose of dextromethorphan 30 mg. In session 2, a 1.5 mg/kg MDMA dose was given at 0 hours, followed at 4 hours by repeated 30 mg doses of dextromethorphan over the next 10 days. METHODS: Plasma concentration-time profiles and urinary recoveries of dextromethorphan and its metabolites dextrorphan (DOR), 3-methoxymorphinan (MM) and hydroxymorphinan-3-ol (HM) were measured. RESULTS: MDMA given prior to dextromethorphan resulted in a 10-fold increase in the dextromethorphan maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), with corresponding decreases in DOR and HM pharmacokinetic parameters. The mean ± SD C(max) of MDMA was 188.8 ± 16.7 ng/mL, with a time to reach C(max) (t(max)) of 2.0 ± 0.4 hours and an AUC from 0 to 25 hours of 2645.2 ± 170.9 mg · h/mL. The urinary recovery of the dextromethorphan dose as dextromethorphan and its main metabolites was 25.4 ± 8.9% with no MDMA pretreatment versus 6.6 ± 1.1% after 1.5 mg/kg of MDMA (p = 0.0001). The metabolic ratio (MR) increased almost 60-fold from 0.018 ± 0.028 to 0.998 ± 0.932 after MDMA administration, with 100% of the subjects having a value greater than the antimode of 0.3 that signified the poor-metabolizer phenotype. Data analysis of results obtained in the present study compared with those from a previous study in male subjects showed significant differences in the dextromethorphan/DOR MR in the 0- to 8-hour (session 1) and 4- to 12-hour (session 2, post MDMA) collection periods (p = 0.032 and p = 0.01, respectively). CYP2D6 activity recovered after 10 days to 90% of baseline activity, with a recovery half-life of 36.6 ± 22.9 hours. Male subjects showed a shorter recovery half-life (27.6 ± 25.1 hours). The measurement of CYP3A4 activity indicated a non-significant increase in C(max) and AUC values of MM after drug intake, but urinary data reflected significant differences in dextromethorphan/MM MR in both sexes, although the difference was more pronounced in women. Dextromethorphan/MM MR increased almost 3-fold from baseline. DISCUSSION AND CONCLUSION: In women the pretreatment with MDMA resulted in a decrease in dextromethorphan clearance. CYP2D6 activity recovered after 10 days to 90% of baseline activity. Regarding CYP3A4 activity, there is an apparent decrease in its activity after MDMA use. In women, MDMA use has been associated with psychiatric symptoms and psychological problems that may require psychopharmacological treatment with antidepressant drugs, some of which are known CYP2D6 substrates. MDMA-induced mechanism-based inhibition of CYP2D6 is of relevance, and physicians should be advised to prescribe medications whose metabolic disposition is not regulated by CYP2D6.


Subject(s)
Cytochrome P-450 CYP2D6 Inhibitors , Hallucinogens/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Administration, Oral , Adult , Analysis of Variance , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/metabolism , Dextromethorphan/pharmacokinetics , Female , Genotype , Half-Life , Hallucinogens/administration & dosage , Hallucinogens/pharmacokinetics , Humans , Male , Models, Biological , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , N-Methyl-3,4-methylenedioxyamphetamine/pharmacokinetics , Phenotype , Sex Factors , Spain , Substrate Specificity , Young Adult
18.
Ther Drug Monit ; 32(4): 508-11, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20535053

ABSTRACT

The pharmacokinetics of methylphenidate (MPH), a prescription amphetamine derivative used in the treatment of attention-deficit hyperactivity disorder, has been amply described in conventional biological matrices. Recently, the excretion of MPH and its principal metabolite, ritalinic acid (RA) in oral fluid and plasma after a single drug administration has been described. The aim of this study was to describe the excretion of MPH and RA in sweat after the administration of a single dose of either fast-release or extended-release MPH. Three male subjects received 2 simultaneous oral doses of 10 mg fast-release MPH, and 1 male subject received one dose of 20 mg extended-release MPH. Sweat patches were applied to the back of each participant and removed at timed intervals. MPH and RA were determined in patches using a previously validated liquid chromatography-electrospray ionization mass spectrometric method. MPH was detected in sweat after the administration of fast- and extended-release formulations. For the fast-release formulation, MPH appeared in the sweat patches 2 hours after administration with a maximum of 15.9 nanogram per patch, reached after 24 hours. Mean total MPH excreted was 0.02 mg (about 0.08% of the administered dose). For the extended-release formulation, MPH appeared in the sweat 5 hours after administration and reached a maximum of 34.3 nanogram per patch after 24 hours. Mean total MPH excreted was 0.04 mg (about 0.18% of the administered dose). RA was not detected in either of the sweat patches probably because of its acidic properties. Measuring MPH in sweat patches can be a viable alternative to urine testing for noninvasive monitoring of use and misuse of the drug.


Subject(s)
Central Nervous System Stimulants/analysis , Methylphenidate/analysis , Substance Abuse Detection/methods , Sweat/chemistry , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/pharmacokinetics , Delayed-Action Preparations , Dose-Response Relationship, Drug , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/analogs & derivatives , Methylphenidate/pharmacokinetics , Pilot Projects , Young Adult
19.
Clin Chem ; 56(4): 585-92, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20167695

ABSTRACT

BACKGROUND: We studied the excretion profile of methylphenidate (MPH) and its metabolite ritalinic acid (RA) in oral fluid and plasma, the oral fluid-to-plasma (OF/P) drug ratio, and the variations of oral fluid pH after drug administration. METHODS: We analyzed oral fluid and plasma samples, obtained from 8 healthy volunteers after ingestion of a single dose of 20 mg fast-release or extended-release MPH, for MPH and RA by LC-MS. We estimated the apparent pharmacokinetic parameters of MPH in plasma and oral fluid and calculated the OF/P ratio for each time interval. RESULTS: MPH and RA were detected in oral fluid. Whereas parent drug concentrations in oral fluid were an order of magnitude higher than those in plasma, the opposite was observed for RA. Oral fluid concentrations of MPH ranged between 0.5 and 466.7 microg/L and peaked at 0.5 h after administration of the fast-release formulation; they ranged between 0.7 and 89.5 microg/L and peaked at 2 h after administration of the extended-release formulation. Both formulations presented bimodal time-course curves for the OF/P ratio, ranging between 1.8 and 242.1 for the fast-release formulation and between 2.6 and 27.0 for extended-release. Oral fluid pH did not appear to be modified by the administration of the drug, and its influence on OF/P ratio did not affect the correlation of MPH between the 2 body fluids. CONCLUSIONS: The results obtained support the measurement of MPH in oral fluid as an alternative to plasma if the extended-release formulation is used.


Subject(s)
Methylphenidate/analogs & derivatives , Methylphenidate/blood , Methylphenidate/cerebrospinal fluid , Adult , Chromatography, Liquid , Humans , Hydrogen-Ion Concentration , Male , Methylphenidate/pharmacokinetics , Reference Values , Spectrometry, Mass, Electrospray Ionization , Young Adult
20.
Adicciones ; 21(3): 181-6, 2009.
Article in Spanish | MEDLINE | ID: mdl-19718488

ABSTRACT

Some smokable herbal mixtures under the brand name Spice drugs have been sold on the Internet and in specialised shops (smart shops) since 2004. The mixtures are advertised as an exotic incense blend which releases a rich aroma and not for human consumption. When smoked, Spice drugs products have been reported by products have been reported by some users to have effects similar to those of cannabis. Spice drugs have received intensive attention in drug forums due to the possibility to obtain a non legal substitute of cannabis. Forensic analyses have found different potent synthetic cannabinoid agonists in some Spice drugs products, as JWH-018, CP 47497, JWH-073 and HU-210. There are few data about its pharmacological properties in animals, but nothing about its toxicity. At present, almost nothing is known about the pharmacology, toxicology and safety profile of such compounds in humans, except the opinions of consumers in internet forums. Neither the herbal ingredients of Spice drugs, nor any of the synthetic cannabinoids found in them, are internationally controlled under the 1961 or 1971 UN drug control conventions. Some European countries have recently taken legal actions to ban or otherwise control Spice drugs products and related compounds. These cannabinoid substances can be considered as new products to be added to the list of 'designer drugs'.


Subject(s)
Cannabinoids , Designer Drugs
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