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Tocilizumab is a monoclonal antibody against the interleukin-6 receptor. Gastrointestinal perforation has been associated with Tocilizumab treatment. In the absence of specific antiviral drugs, Tocilizumab is currently being used as a treatment option in patients with severe COVID-19 pneumonia. This is being based on the implication of interleukin-6 in the aberrant host immune response that characterizes the disease and initiates patients' lung damage. Herein we present the case of a cecal perforation in a patient treated with Tocilizumab for COVID-19. In such context, we expect that there may be an increase in the incidence of gastrointestinal perforation related to Tocilizumab.

Introduction Since the first laparoscopic incisional hernia repair, several minimally invasive procedures have been developed in abdominal wall repair. In 2017, the extended totally extraperitoneal (eTEP) approach for abdominal wall repair was published. We present the results from eTEP implementation at two medical centers by one surgeon. Methods Prospective descriptive study of the implementation of the eTEP approach, with transversus abdominis release (TAR) when needed. The surgical technique was initiated by accessing the space between the rectus abdominis muscle and posterior rectus sheath, connecting this space with the fatty preperitoneal space at the midline and the contralateral retrorectal space. Identification and dissection of the hernia sac is performed in the created cavity. Additionally, posterior component release in a TAR fashion could be done. Finally, closure of posterior plane and linea alba is completed and mesh prosthesis is deployed along the whole dissected space. Results Forty patients underwent an eTEP procedure with 20 supraumbilical defects, 10 infraumbilical and 10 lateral hernias. Sixteen cases required a TAR technique. Mean operative time was 126 min. Median pain reported the first postoperative day was 3 on the visual analog scale. Median length of stay was 1 day and mean follow-up was 10 months. Only one patient developed recurrence, and two patients underwent reoperation. Conclusions Implementation of eTEP in abdominal wall repair is safe. Preliminary outcomes of the eTEP approach in ventral hernia repair show good pain control with less hospital stay.

Resumen Introduccion Desde la primera eventroplastia laparoscopica se han desarrollado multiples procedimientos en cirugia miniinvasiva de la pared abdominal. En 2017 se publica el acceso endoscopico totalmente extraperitoneal extendido (eTEP) para la reparacion abdominal. Se presentan los resultados de la implementacion de la tecnica en 2 centros por un unico cirujano. Metodos Estudio prospectivo descriptivo de la implementacion de la via eTEP con o sin liberacion de transverso (TAR) para defectos de la pared abdominal. La tecnica quirurgica se inicia con el acceso al espacio entre el musculo recto y la vaina posterior, uniendo dicho espacio con el preperitoneo de la linea media y el espacio retrorrectal contralateral. En la cavidad creada se realiza la diseccion y reduccion del saco herniario. Se puede realizar adicionalmente una liberacion posterior de componentes tipo TAR. Se realiza el cierre del peritoneo y del defecto fascial y se extiende una protesis en el espacio definitivo. Resultados Se intervinieron 40 casos, 20 casos con defectos supraumbilicales, 10 casos infraumbilicales y 10 en la linea semilunar. Dieciseis casos asociaron TAR. El tiempo quirurgico medio fue de 126 minutos. El dolor mediano por la escala EVA al alta fue de 3. La estancia mediana fue de un dia y el seguimiento medio de 10 meses. Un caso mostro recidiva y 2 pacientes requirieron reintervencion. Conclusiones La reparacion de hernias primarias e incisionales abdominales mediante eTEP es segura y reproducible. Los resultados preliminares muestran buen control del dolor postoperatorio y baja estancia.

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.

Resumen Introduccion Los tumores de bazo primarios o metastasicos suponen menos del 0,96% de todas las metastasis. Caso clinico Mujer de 80 anos de edad intervenida 3,5 anos antes por carcinoma ductal infiltrante con tratamiento neoadyuvante. Durante el seguimiento se encontro en PET-TAC recidiva tumoral en hilio esplenico. Se realizo esplenectomia laparoscopica que fue informada como adenocarcinoma de origen mamario. Discusion Las metastasis esplenicas son infrecuentes, suelen manifestarse como esplenomegalia asociadas a molestias abdominales. Los tumores esplenicos malignos presentan fiebre, sindrome constitucional, derrame pleural y caquexia. El diagnostico de metastasis esplenicas suele realizarse durante el seguimiento oncologico con tomografia computarizada (TC). El tratamiento es la reseccion quirurgica, aunque no existen protocolos para el tratamiento de las metastasis esplenicas. La supervivencia tras la esplenectomia por metastasis aumenta. Conclusiones La esplenectomia ante metastasis esplenicas es el tratamiento realizado habitualmente ante estos casos.

Background Bone disease in primary hyperparathyroidism is a clear indication for surgical treatment. However, it is not known whether surgery benefits hypercalcemic primary hyperparathyroidism and normocalcemic primary hyperparathyroidism equally. The aim of our study was to evaluate the bone changes in patients undergoing parathyroidectomy based on the biochemical profile 1 and 2 years after surgery. Methods This prospective study included 87 consecutive patients diagnosed with primary hyperparathyroidism who underwent surgery between 2016 and 2018. Bone densitometry (1/3 distal radius, lumbar, and femur) and bone remodeling markers (osteocalcin, type 1 procollagen [P1NP], β-cross-linked telopeptide of type I collagen [BCTX]) were performed preoperatively and postoperatively. Postoperative changes in bone mineral density and bone markers were compared and evaluated according to the clinical characteristics and the individual biochemical profile. Results One year after surgery, all patients showed an increase in bone mineral density at the lumbar site (mean, 0.029 g/cm2; range, 0.017–0.04; P Conclusion Our findings indicate that parathyroidectomy has similar benefits for normocalcemic primary hyperparathyroidism and hypercalcemic primary hyperparathyroidism in terms of bone improvement. Although the most substantial improvement occurred during the first postoperative year in both groups, we consider that studies with longer follow-up are warranted.

COVID-19 is the infectious disease caused by the recently discovered coronavirus, SARS-CoV-2, unknown before the outbreak in Wuhan, China, in December 2019. COVID-19 is a pandemic, infectious disease that has simultaneously affected many countries globally. The leading cause of dead in patients with COVID-19 is hypoxic respiratory failure from acute respiratory distress syndrome (ARDS). Diffuse alveolar damage (DAD) is the histopathological pattern commonly described in all the postmortem series up to date. DAD is divided into two phases, and depending on the length of the disease, the morphological features seen in the specimens vary. There is an acute/exudative phase, which occurs during the first week after the pulmonary injury, following by the organizing/proliferative phase. Additional features detailed include vascular thrombosis, endothelialitis and angiogenesis. Interestingly, there is an ongoing discussion about the specificity of these changes, as diffuse alveolar damage seen in other viral infections show similar features.

Resumen Introduccion El histiocitoma fibroso maligno constituye la neoplasia sarcomatosa mas frecuente en los adultos, pero la mama es una localizacion excepcional. Presentamos el caso de una mujer que comenzo con una tumoracion de crecimiento progresivo en la mama derecha. Caso clinico Mujer de 68 anos que consulta por autopalpacion de un nodulo en la mama derecha que ha crecido de forma progresiva en los ultimos meses. La mamografia y la ecografia muestran una imagen nodular con bordes bien definidos, situada en intercuadrantes superiores de mama derecha, sin adenopatias axilares. Se decidio intervencion quirurgica y el estudio histologico definitivo fue informado como neoformacion mesenquimal fusocelular con patron estoriforme. El estudio inmunohistoquimico fue compatible con un histiocitoma fibroso maligno. Conclusion Es primordial el diagnostico diferencial de esta entidad clinica debido a la variabilidad histologica de los tumores sarcomatosos. Sus caracteristicas clinicas y radiologicas pueden hacerlo pasar desapercibido, pero su comportamiento agresivo hace necesario un diagnostico precoz, lo cual permitira un tratamiento adecuado para lograr el aumento en la supervivencia.

Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.

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.

Introduction the presence of diverticula and their complications in the cecal appendix is an uncommon disease. We present a series of 13 patients with this condition, and perform a review of the literature. Patients and method we carried out a retrospective study of patients undergoing appendectomy for acute appendicitis in the last twelve years in our department. The pathological examination of these episodes revealed 13 cases with a diagnosis of diverticular disease, all of them consisting of pseudodiverticula. Their clinical manifestations, laboratory results, imaging tests, and histology were analyzed, and findings were compared to those in the previous literature. Results the incidence of diverticular disease in our setting was 13 cases (0.8%) among 1634 appendectomies for acute appendicitis. Diverticulitis was found in 8 patients (61.5%), and diverticulosis (38.5%) in 5. Appendicular perforation was more common in patients with diverticular disease (53.8%) as compared to those without this condition (31.1%). Conclusions complicated diverticular disease in the vermiform appendix of adult patients may result in insidious, recurrent manifestations that may confound preoperative diagnosis. A higher risk for appendicular perforation renders appendectomy the therapy of choice, even prophylactically when the condition is incidentally identified preoperatively.

The current interest in developing Glycine transporter Type 1 (GlyT- 1) inhibitors, for diseases such as schizophrenia, has led to the demand for a GlyT-1 PET molecular imaging tool to aid drug development and dose selection. We report on ( 11 C)GSK931145 as a novel GlyT-1 imaging probe in primate and man. Primate PET studies were performed to determine the level of specific binding following homologous competition with GSK931145 and the plasma-occupancy relationship of the GlyT-1 in- hibitor GSK1018921. Human PET studies were performed to determine the test-retest reproducibility of ( 11 C)GSK931145 and the plasma-occupancy relationship of GSK1018921. ( 11 C)GSK931145 entered primate and human brain and yielded a heter- ogeneous pattern of uptake which was similar in both species with highest uptake in midbrain, thalamus, and cerebellum. Homologous competition in primates indicated no viable reference region and gave binding potential estimates between 1.5 and 3 for midbrain, thalamus and cerebellum, While the distribution and binding potential val- ues were similar across species, both the plasma free fraction (fP: 0.8 vs. 8%) and delivery (K1: 0.025 vs. 0.126 ml cm 23 min 21 ) were significantly lower in humans. Test-retest reproducibility in humans calculated using a two tissue compartmental model was poor (VAR(VT): 29-38%), but was improved using a pseudo reference tissue model (VAR(BPND): 16-23%). GSK1018921 EC50 estimates were 22.5 and 45.7 ng/ml in primates and humans, respectively. Synapse 65:1319-1332, 2011. V C 2011 Wiley-Liss, Inc.

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 1.5mg/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 (Cmax) and area under the plasma concentration-time curve (AUC), with corresponding decreases in DOR and HM pharmacokinetic parameters. The mean ± SD Cmax of MDMA was 188.8 ± 16.7 ng/mL, with a time to reach Cmax (tmax) 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 1.5mg/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 Cmax 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: resulted in a decrease 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 psycho-pharmacological 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.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a widely abused substituted amphetamine. MDMA is predominantly O-demethylenated in humans by cytochrome P450 isoforms 2D6 and 1A2 (CYP2D6 and CYP CYP1A2, respectively). MDMA is also a mechanism-based inhibitor of CYP2D6. A controlled clinical trial was conducted in 15 healthy male subjects whereby a probe drug, dextromethorphan (DEX), was administered after an oral dose of 1.5 mg/kg MDMA. The pharmacokinetics of DEX and its metabolites were used to evaluate changes in CYP2D6 activity. The urinary metabolic ratio of DEX and dextrorphan was used to calculate a recovery half-life of CYP2D6. After MDMA, DEX Cmax and area under the curve increased approximately 10-fold with corresponding decreases in dextrorphan pharmacokinetic parameters. The metabolic ratio increased almost 100-fold from 0.0061 +/- 0.0056 to 0.4322 +/- 0.2848 after MDMA administration, with 67% of the subjects having a value greater than the antimode of 0.3 for assigning the poor metabolizer phenotype. CYP2D6 activity recovered after 10 days with a recovery half-life of 46.6 hours. In addition to the possible long-term serotonergic effects of MDMA, users must be warned of the consequences of such an inhibition.

In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI) of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer (PM) phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.Yubero-Lahoz S, Pardo-Lozano R, Farré M

The synthetic psychostimulant MDMA (±3,4-methylenedioxymethamphetamine, ecstasy) acts as an indirect serotonin, dopamine, and norepinephrine agonist and as a mechanism-based inhibitor of the cytochrome P-450 2D6 (CYP2D6). It has been suggested that women are more sensitive to MDMA effects than men but no clinical experimental studies have satisfactorily evaluated the factors contributing to such observations. There are no studies evaluating the influence of genetic polymorphism on the pharmacokinetics (CYP2D6; catechol-O-methyltransferase, COMT) and pharmacological effects of MDMA (serotonin transporter, 5-HTT; COMT). This clinical study was designed to evaluate the pharmacokinetics and physiological and subjective effects of MDMA considering gender and the genetic polymorphisms of CYP2D6, COMT, and 5-HTT. A total of 27 (12 women) healthy, recreational users of ecstasy were included (all extensive metabolizers for CYP2D6). A single oral weight-adjusted dose of MDMA was administered (1.4 mg/kg, range 75–100 mg) which was similar to recreational doses. None of the women were taking oral contraceptives and the experimental session was performed during the early follicular phase of their menstrual cycle. Principal findings show that subjects reached similar MDMA plasma concentrations, and experienced similar positive effects, irrespective of gender or CYP2D6 (not taking into consideration poor or ultra-rapid metabolizers) or COMT genotypes. However, HMMA plasma concentrations were linked to CYP2D6 genotype (higher with two functional alleles). Female subjects displayed more intense physiological (heart rate, and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determined greater cardiovascular effects, and with low functionality (met/* or s/s) negative subjective effects (dizziness, anxiety, sedation). In conclusion, the contribution of MDMA pharmacokinetics following 1.4 mg/kg MDMA to the gender differences observed in drug effects appears to be negligible or even null. In contrast, 5-HTTLPR and COMT val158met genotypes play a major role. This study was supported by NIDA grant 5R01BA017987-01, by grants from DIUE de la Generalitat de Catalunya (2009 SGR 718), Spanish Network on Addiction Disorders grant (FIS-RTA RD06/0001/1009), and Ministerio de Educación y Ciencia grant (MICINN FI09/00355), and the support of ISCIII-FIS-CAIBERCAI08/01/0024. R. Pardo-Lozano is a recipient of a fellowship Rio Hortega (FIS CM08/00051

ObjectivesEvidence of the effects of soft drinks consumption on BMI and lifestyle in adult populations is mixed and quite limited. The aim of the present study was to determine the association of soft drinks consumption with BMI and lifestyle in a representative Mediterranean population.DesignTwo independent, population-based, cross-sectional (2000 and 2005) studies. Dietary intake was assessed using a validated FFQ. Weight and height were measured.SettingGirona, Spain.SubjectsRandom sample of the 35- to 74-year-old population (3910 men and 4285 women).ResultsLess than half (41·7 %) of the population consumed soft drinks; the mean consumption was 36·2 ml/d. The prevalence of sedentary lifestyle increased with the frequency of soft drinks consumption (P= 0·025). Daily soft drinks consumption significantly increased the risk of low adherence to the Mediterranean diet (OR = 0·57, 95 % CI 0·44, 0·74v. top tertile of Mediterranean diet score). Multiple linear regression analyses, controlled for potential confounders, revealed that an increment in soft drinks consumption of 100 ml was associated with a 0·21 kg/m2increase in BMI (P= 0·001). Only implausibly low reports of energy consumption showed a null association between soft drinks consumption and BMI.ConclusionsSoft drinks consumption was not embedded in a healthy diet context and was positively associated with BMI and sedentary lifestyle in this Mediterranean population.

To evaluate the impact of radioguided occult lesion localization (ROLL) in the correct location and excision of malignant breast lesions, and analyze if these results are affected by the histology and tumor size. A total of 105 patients with occult breast lesions were studied. The mean age was 55 years. An intralesional dose of 18.5 MBq of 99mTc-labeled macroaggregated human albumin (AMA) was administered using stereotaxic mammography or ultrasound. Surgical resection was carried out with the help of a gammadetector probe. In the histological study, disease-free margin was defined by a distance between the tumor lesion and the surgical margin of more than 1 mm. The possible influence of tumor histology and lesion diameter with respect to free/affected margins was analyzed. Correct radiotracer placement was achieved in 100/105 of the cases (95.2%). In the remaining 5 cases (4.8%), radiotracer placement was incorrect, with 2 of them being malignant lesions that were found by macroscopic inspection, and the other 3 having benign pathology. Among the malignant lesions (44 cases), correct placement of the radiotracer was achieved in 42 cases (95.5%). Of these 42 malignant lesions, in which the ROLL was correctly performed, free surgical margins were obtained in 24 cases (57.1%), while the other 18 (42.9%) had infiltrated surgical margins. The most common histological type among the malignant lesions was invasive ductal carcinoma (71.4%). The histological types with an increased frequency of infiltration of surgical margins were invasive and microinvasive cancer (94.4%). All the affected margins were in lesions greater than 10 mm, and the highest incidence was in those between 20 and 30 mm (55.5%). In our experience, the advantages of the ROLL technique are a precise localization of malignant breast lesions (95.5%) and an increased probability of a complete excision with free margins in more than one half of them. Nevertheless, special consideration should be taken when dealing with invasive and microinvasive cancers and in those exceeding 10 mm because of their higher incidence of infiltrated margins.

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.

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 μg/L and peaked at 0.5 h after administration of the fast-release formulation; they ranged between 0.7 and 89.5 μg/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.

El café, el té, el chocolate y los refrescos de cola son las principales fuentes de cafeína, que es consumida en casi todas las edades y estratos socioeconómicos. La cafeína es un antagonista competitivo de los receptores adenosínicos del SNC. Sus principales efectos son psicoestimulantes, respiratorios, músculo-esqueléticos y cardiovasculares. Básicamente, se metaboliza por el CYP1A2 por lo que interacciona con numerosos fármacos. Las variaciones interindividuales en su metabolismo explican las diferencias de sus efectos. Su principal uso terapéutico es como broncodilatador en patología respiratoria. Además, se ha experimentado en otras patologías con resultados no concluyentes. El consumo agudo o crónico de cafeína puede dar lugar a una amplia variedad de efectos adversos, intoxicaciones e incluso la muerte. Finalmente, destacar que la cafeína puede considerarse una droga de abuso. Así, la cafeína posee propiedades reforzadoras positivas, produce tolerancia y al cesar su consumo aparece un síndrome de abstinencia específico. La cafeína puede dar lugar a diferentes trastornos por uso de sustancias. Entre ellas la dependencia, no reconocida en el DSM IV-R, el síndrome de abstinencia y la intoxicación. La cafeína puede considerarse un fármaco, un nutriente y una droga de abuso dependiendo de su uso Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse

We observed 37 patients (mean age at onset, 48.5 years; range, 13 to 84 years) with segmental myoclonus (18 branchial, 19 spinal). Etiologies for branchial myoclonus included brain-stem demyelination, cerebrovascular disease, Meige's syndrome, cerebral arteritis secondary to bacterial meningitis, central nervous system Whipple's disease, acute cervicomedullary trauma, and cerebellar degeneration. Spinal myoclonus was associated with laminectomy, remote effect of cancer, spinal cord injury, post-operative pseudomeningocele, laparotomy, thoracic sympathectomy, poliomyelitis, herpes myelitis, lumbosacral radiculopathy, spinal extradural block, and myelopathy due to demyelination, electrical injury, acquired immunodeficiency syndrome, and cervical spondylosis. The latency between the predisposing condition and the onset of myoclonus ranged from immediate to 33 years (mean, 2.9 years). In six patients, the myoclonus was the presenting symptom of a serious underlying disease. Treatment with clonazepam, tetrabenazine hydrochloride, or other medications provides a satisfactory control in most patients.