Intense scuba diving does not alter activity patterns of predatory reef fish: Evidence from a protected tourism hotspot.

The rise of nature-based tourism has provided a new avenue for disturbing animal behaviour, especially in protected areas. One of the most important tourism sectors in aquatic environments is scuba diving, an activity considered sustainable given its non-extractive nature and capability of bringing relevant socio-economic benefits to local communities. However, knowledge about its impact on the activity patterns of aquatic animals is still scarce. Here, we used biotelemetry techniques to assess the importance of scuba diving in modulating the activity patterns of the dusky grouper (Epinephelus marginatus, Lowe, 1834), a marine predatory fish of high interest for fishing and tourism. We implemented Hidden Markov Models (HMMs) on high-resolution acceleration data using a temporal and spatial control while controlling for a set of environmental variables (i.e. photoperiod, time-of-day, moon phase, temperature, wave height, and intensity and direction of marine currents) within a multiple-use marine protected area, and diving tourism hot-spot, of the western Mediterranean Sea. Our results underlined the more decisive influence of environmental-related stressors on the activity patterns of the dusky grouper compared to the impact of scuba diving. A high heterogeneity existed in the response against most of the stressors, including the presence of scuba divers. Overall, the activity of dusky grouper was higher at night than at day, showing a positive relationship with wave height, water temperature, and current intensity and a negative one with the moon phase. Remarkably, our findings, based on novel biotelemetry tools, differed substantially from the common wisdom accepted for this species. In conclusion, there is no clear evidence of scuba divers influence on the general activity patterns of the dusky grouper. Beyond their relevance from an ecological perspective, these results provide useful insights for the sustainable management of coastal resources, suggesting that scuba diving, when properly carried out, can represent an important sector to foster for the blue growth of coastal communities.

Perioperative management of non-deferrable oncologic surgeries during COVID-19 pandemic in Madrid, Spain. Is it safe?

INTRODUCTION: Surgical treatment during Covid-19 pandemic is controversial. Currently, most clinical guidelines advise to defer surgical patients during the Covid-19 pandemic, although the supporting data is sparse. We assumed that a Covid-19-free hospital, on the back of strong isolation measures and targeted screening, could reduce complications and enable us to continue treating high-risk patients. METHODS: Prospective study with retrospective analysis of 355 patients who had undergone nondeferrable oncological surgery between March 16th, 2020, and April 14th, 2020, at our institution. The aim of the study was to assess the hospital restructuring and surgical protocols to be able to safely handle non-deferrable surgeries during the first wave of the Covid-19 pandemic. We implemented structural changes and an updated surgical-anesthetic protocol in order to isolate Covid-19 patients from other surgical patients. Comprehensive targeted screening for Covid-19 patients was made. PCR tests were requested for suspected Covid-19 patients. We analyzed mortality and complications related to both surgery and Covid-19 during hospital admission and also 15 and 30 days after surgery. We compared it with a sample of similar patients in the pre-pandemic period. RESULTS: Of the 355 patients enrolled in our study, 21 were removed due to Covid-19 infection, leaving a total of 334 patients in our final analysis. Post-operative complications were found in 37 patients (11.07%). Two patients died after surgery (0.6%). At the end of the study, Covid-19-related adverse outcomes were detected in six patients (1.79%). When comparing the complications of our original sample with the complications that occurred in the pre-covid era, we found no statistically significant differences. CONCLUSIONS: Our results show that the surgical treatment of oncologic patients during the Covid-19 pandemic is safe, as long as the hospital performs surgeries under strict isolation measures and a robust screening method. It is necessary to select Covid-19 free hospitals for this matter in this and future pandemics.

Manejo perioperatorio de cirugías oncológicas no diferibles durante la pandemia de covid-19 en Madrid, España ¿Es seguro? / Perioperative management of non-deferrable oncologic surgeries during COVID-19 pandemic in Madrid, Spain. Is it safe?

Introducción: El tratamiento quirúrgico durante la pandemia de COVID-19 es controvertido. Actualmente, la mayoría de las guías clínicas recomiendan posponer la cirugía a los pacientes durante la pandemia de COVID-19, aunque los datos de apoyo son escasos. Asumimos que un hospital sin COVID-19, apoyado en fuertes medidas de aislamiento y exámenes de detección específicos, podría reducir las complicaciones y nos permitiría continuar tratando a pacientes de alto riesgo. Métodos: Estudio prospectivo con análisis retrospectivo de 355 pacientes sometidos a cirugía oncológica no diferible entre el 16 de marzo de 2020 y el 14 de abril de 2020 en nuestra institución. El objetivo del estudio fue valorar la reestructuración hospitalaria y de los protocolos quirúrgicos para poder manejar con seguridad las cirugías no diferibles durante la primera ola de pandemia por COVID-19. Implementamos cambios estructurales y un protocolo anestésico-quirúrgico actualizado para aislar a los pacientes con COVID-19 de otros pacientes quirúrgicos. Se realizó una evaluación exhaustiva dirigida a detectar pacientes con COVID-19. Se solicitaron pruebas de PCR para pacientes sospechosos de COVID-19. Analizamos la mortalidad y las complicaciones relacionadas tanto con la cirugía como con la COVID-19 durante el ingreso hospitalario y también a los 15 días y al mes de la cirugía. Comparamos nuestros resultados con una muestra de pacientes similar en el periodo pre-pandemia. Resultados: De los 355 pacientes incluidos en nuestro estudio, 21 fueron eliminados debido a la infección por COVID-19, lo que deja un total de 334 pacientes en nuestro análisis final. Se encontraron complicaciones postoperatorias en 37 pacientes (11,07%). Dos pacientes fallecieron tras la cirugía (0,6%).(AU)

Introduction: Surgical treatment during COVID-19 pandemic is controversial. Currently, most clinical guidelines advise to defer surgical patients during the COVID-19 pandemic, although the supporting data is sparse. We assumed that a COVID-19-free hospital, on the back of strong isolation measures and targeted screening, could reduce complications and enable us to continue treating high-risk patients. Methods: Prospective study with retrospective analysis of 355 patients who had undergone nondeferrable oncological surgery between March 16th, 2020, and April 14th, 2020, at our institution. The aim of the study was to assess the hospital restructuring and surgical protocols to be able to safely handle non-deferrable surgeries during the first wave of the COVID-19 pandemic. We implemented structural changes and an updated surgical-anesthetic protocol in order to isolate COVID-19 patients from other surgical patients. Comprehensive targeted screening for COVID-19 patients was made. PCR tests were requested for suspected COVID-19 patients. We analyzed mortality and complications related to both surgery and COVID-19 during hospital admission and also 15 and 30 days after surgery. We compared it with a sample of similar patients in the pre-pandemic period. Results: Of the 355 patients enrolled in our study, 21 were removed due to COVID-19 infection, leaving a total of 334 patients in our final analysis. Post-operative complications were found in 37 patients (11.07%). Two patients died after surgery (0.6%). At the end of the study, COVID-19-related adverse outcomes were detected in six patients (1.79%). When comparing the complications of our original sample with the complications that occurred in the pre-COVID era, we found no statistically significant differences.(AU)

[Perioperative management of non-deferrable oncologic surgeries during COVID-19 pandemic in Madrid, Spain. Is it safe?] / Manejo perioperatorio de cirugías oncológicas no diferibles durante la pandemia de covid-19 en Madrid, España ¿Es seguro?

INTRODUCTION: Surgical treatment during COVID-19 pandemic is controversial. Currently, most clinical guidelines advise to defer surgical patients during the COVID-19 pandemic, although the supporting data is sparse. We assumed that a COVID-19-free hospital, on the back of strong isolation measures and targeted screening, could reduce complications and enable us to continue treating high-risk patients. METHODS: Prospective study with retrospective analysis of 355 patients who had undergone nondeferrable oncological surgery between March 16th, 2020, and April 14th, 2020, at our institution. The aim of the study was to assess the hospital restructuring and surgical protocols to be able to safely handle non-deferrable surgeries during the first wave of the COVID-19 pandemic. We implemented structural changes and an updated surgical-anesthetic protocol in order to isolate COVID-19 patients from other surgical patients. Comprehensive targeted screening for COVID-19 patients was made. PCR tests were requested for suspected COVID-19 patients. We analyzed mortality and complications related to both surgery and COVID-19 during hospital admission and also 15 and 30 days after surgery. We compared it with a sample of similar patients in the pre-pandemic period. RESULTS: Of the 355 patients enrolled in our study, 21 were removed due to COVID-19 infection, leaving a total of 334 patients in our final analysis. Post-operative complications were found in 37 patients (11.07%). Two patients died after surgery (0.6%). At the end of the study, COVID-19-related adverse outcomes were detected in six patients (1.79%). When comparing the complications of our original sample with the complications that occurred in the pre-COVID era, we found no statistically significant differences. CONCLUSIONS: Our results show that the surgical treatment of oncologic patients during the COVID-19 pandemic is safe, as long as the hospital performs surgeries under strict isolation measures and a robust screening method. It is necessary to select COVID-19 free hospitals for this matter in this and future pandemics.

Perioperative management of non-deferrable oncologic surgeries during COVID-19 pandemic in Madrid, Spain. Is it safe? / Manejo perioperatorio de cirugías oncológicas no diferibles durante la pandemia de covid-19 en Madrid, España ¿Es seguro?

INTRODUCTION: Surgical treatment during COVID-19 pandemic is controversial. Currently, most clinical guidelines advise to defer surgical patients during the COVID-19 pandemic, although the supporting data is sparse. We assumed that a COVID-19-free hospital, on the back of strong isolation measures and targeted screening, could reduce complications and enable us to continue treating high-risk patients. METHODS: Prospective study with retrospective analysis of 355 patients who had undergone nondeferrable oncological surgery between March 16th, 2020, and April 14th, 2020, at our institution. The aim of the study was to assess the hospital restructuring and surgical protocols to be able to safely handle non-deferrable surgeries during the first wave of the COVID-19 pandemic. We implemented structural changes and an updated surgical-anesthetic protocol in order to isolate COVID-19 patients from other surgical patients. Comprehensive targeted screening for COVID-19 patients was made. PCR tests were requested for suspected COVID-19 patients. We analyzed mortality and complications related to both surgery and COVID-19 during hospital admission and also 15 and 30 days after surgery. We compared it with a sample of similar patients in the pre-pandemic period. RESULTS: Of the 355 patients enrolled in our study, 21 were removed due to COVID-19 infection, leaving a total of 334 patients in our final analysis. Post-operative complications were found in 37 patients (11.07%). Two patients died after surgery (0.6%). At the end of the study, COVID-19-related adverse outcomes were detected in six patients (1.79%). When comparing the complications of our original sample with the complications that occurred in the pre-COVID era, we found no statistically significant differences. CONCLUSIONS: Our results show that the surgical treatment of oncologic patients during the COVID-19 pandemic is safe, as long as the hospital performs surgeries under strict isolation measures and a robust screening method. It is necessary to select COVID-19 free hospitals for this matter in this and future pandemics.

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

Background Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. Methods Observational retrospective multicenter study. Inclusion criteria: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. Results Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. Conclusion It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here (AU)

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

Functional Connectivity Hypersynchronization in Relatives of Alzheimer's Disease Patients: An Early E/I Balance Dysfunction?

Alzheimer's disease (AD) studies on animal models, and humans showed a tendency of the brain tissue to become hyperexcitable and hypersynchronized, causing neurodegeneration. However, we know little about either the onset of this phenomenon or its early effects on functional brain networks. We studied functional connectivity (FC) on 127 participants (92 middle-age relatives of AD patients and 35 age-matched nonrelatives) using magnetoencephalography. FC was estimated in the alpha band in areas known both for early amyloid accumulation and disrupted FC in MCI converters to AD. We found a frontoparietal network (anterior cingulate cortex, dorsal frontal, and precuneus) where relatives of AD patients showed hypersynchronization in high alpha (not modulated by APOE-ε4 genotype) in comparison to age-matched nonrelatives. These results represent the first evidence of neurophysiological events causing early network disruption in humans, opening a new perspective for intervention on the excitation/inhibition unbalance.

Spatiotemporal Oscillatory Patterns During Working Memory Maintenance in Mild Cognitive Impairment and Subjective Cognitive Decline.

Working memory (WM) is a crucial cognitive process and its disruption is among the earliest symptoms of Alzheimer's disease. While alterations of the neuronal processes underlying WM have been evidenced in mild cognitive impairment (MCI), scarce literature is available in subjective cognitive decline (SCD). We used magnetoencephalography during a WM task performed by MCI (n = 45), SCD (n = 49) and healthy elders (n = 49) to examine group differences during the maintenance period (0-4000ms). Data were analyzed using time-frequency analysis and significant oscillatory differences were localized at the source level. Our results indicated significant differences between groups, mainly during the early maintenance (250-1250ms) in the theta, alpha and beta bands and in the late maintenance (2750-3750ms) in the theta band. MCI showed lower local synchronization in fronto-temporal cortical regions in the early theta-alpha window relative to controls (p = 2 × 10-03) and SCD (p = 4 × 10-03), and in the late theta window relative to controls (p = 1 × 1003) and SCD (p = 0.01). Early theta-alpha power was significantly correlated with memory scores (rho = 0.24,p = 0.02) and late theta power was correlated with task performance (rho = 0.24,p = 0.03) and functional activity scores (rho = -0.23,p = 0.02). In the early beta window, MCI showed reduced power in temporo-posterior regions relative to controls (p = 3 × 10-03) and SCD (p = 0.02). Our results may suggest that these alterations would reflect that memory-related networks are damaged.

[Analysis of polymorphism rs1051730 of CHRNA3 in patients with dual pathology in a Mexican population]. / Analisis del polimorfismo rs1051730 de CHRNA3 en pacientes con patologia dual en poblacion mexicana.

INTRODUCTION: Epidemiological studies have described a high comorbidity of substance use disorders with another psychiatric disorder, which has been called dual pathology. However, the aetiological mechanisms underlying this association are still not fully understood. AIM: To carry out a preliminary study of the effect of polymorphism rs1051730 of the gene group CHRNA5-CHRNA3-CHRNB4 through a case-control study. SUBJECTS AND METHODS: A total of 225 subjects were selected and divided into three groups: those diagnosed with bipolar disorder, those with nicotine dependence, and subjects without nicotine dependence or any other psychiatric disorder. Genotyping was performed by real-time polymerase chain reaction. Genetic association analysis was performed using chi-square tests and multivariate logistic regressions. RESULTS: On comparing allelic frequencies with the control group, we found that polymorphism rs1051730 was associated with nicotine dependence (p = 0.03), but not with bipolar disorder (p = 0.94). CONCLUSION: Variant rs1051730 was associated with nicotine dependence in the Mexican population and showed the same effect in dual pathology. However, further studies are recommended to obtain conclusive results.

TITLE: Analisis del polimorfismo rs1051730 de CHRNA3 en pacientes con patologia dual en poblacion mexicana.Introduccion. Estudios epidemiologicos han descrito una alta comorbilidad de los trastornos de uso de sustancias con otro trastorno psiquiatrico, al cual se le ha llamado patologia dual. Sin embargo, los mecanismos etiologicos de esta asociacion continuan siendo dificiles de entender. Objetivo. Realizar un estudio preliminar del efecto del polimorfismo rs1051730 del grupo de genes CHRNA5-CHRNA3-CHRNB4 a traves de un estudio de casos y controles. Sujetos y metodos. Se selecciono a un total de 225 sujetos, divididos en tres grupos: con diagnostico de trastorno bipolar, con dependencia a la nicotina y sujetos sin dependencia a la nicotina o cualquier otro trastorno psiquiatrico. La genotipificacion se realizo mediante reaccion en cadena de la polimerasa en tiempo real. El analisis de asociacion genetica se realizo mediante pruebas de chi cuadrado y regresiones logisticas multivariables. Resultados. Al comparar las frecuencias alelicas con el grupo control, encontramos que el polimorfismo rs1051730 se asocio con el grupo de dependencia a la nicotina (p = 0,03), pero no con el de trastorno bipolar (p = 0,94). Conclusion. La variante rs1051730 se asocio con dependencia a la nicotina en la poblacion mexicana y mostro el mismo efecto en la patologia dual. Sin embargo, se recomiendan estudios adicionales para tener resultados concluyentes.

Alpha band disruption in the AD-continuum starts in the Subjective Cognitive Decline stage: a MEG study.

The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of AD remains still a matter of debate. Alpha band alterations represent one of the most significant changes in the electrophysiological profile of AD. In particular, AD patients exhibit reduced alpha relative power and frequency. We used alpha band activity measured with MEG to study whether SCD and MCI elders present these electrophysiological changes characteristic of AD, and to determine the evolution of the observed alterations across AD spectrum. The total sample consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51 MCI patients. All of them underwent MEG and MRI scans and neuropsychological assessment. SCD and MCI patients exhibited a similar reduction in alpha band activity compared with the no SCD group. However, only MCI patients showed a slowing in their alpha peak frequency compared with both SCD and no SCD. These changes in alpha band were related to worse cognition. Our results suggest that AD-related alterations may start in the SCD stage, with a reduction in alpha relative power. It is later, in the MCI stage, where the slowing of the spectral profile takes place, giving rise to objective deficits in cognitive functioning.

Intramolecular Communication in Anionic Oxidized Phosphanes through a Chelated Proton.

Oxidation of the 1,2-(PR2 )2 -1,2-closo-C2 B10 H10 (R=Ph, iPr) platform with hydrogen peroxide in acetone is a two-step procedure in which partial deboronation of the closo cluster and oxidation of the phosphorus atoms occur. Based on NMR spectroscopic and kinetic data, we demonstrate that the phosphorus atoms are oxidized in the first step, followed by cluster deboronation. DFT calculations and natural-bond orbital (NBO) analysis were used to obtain insight into the electronic structures of diphosphane ortho-carborane derivatives.

A quantitative speciation model for the adsorption of organic pollutants on activated carbon.

Granular activated carbon (GAC) is commonly used as adsorbent in water treatment plants given its high capacity for retaining organic pollutants in aqueous phase. The current knowledge on GAC behaviour is essentially empirical, and no quantitative description of the chemical relationships between GAC surface groups and pollutants has been proposed. In this paper, we describe a quantitative model for the adsorption of atrazine onto GAC surface. The model is based on results of potentiometric titrations and three types of adsorption experiments which have been carried out in order to determine the nature and distribution of the functional groups on the GAC surface, and evaluate the adsorption characteristics of GAC towards atrazine. Potentiometric titrations have indicated the existence of at least two different families of chemical groups on the GAC surface, including phenolic- and benzoic-type surface groups. Adsorption experiments with atrazine have been satisfactorily modelled with the geochemical code PhreeqC, assuming that atrazine is sorbed onto the GAC surface in equilibrium (log Ks = 5.1 ± 0.5). Independent thermodynamic calculations suggest a possible adsorption of atrazine on a benzoic derivative. The present work opens a new approach for improving the adsorption capabilities of GAC towards organic pollutants by modifying its chemical properties.

[Multicenter study of satisfaction with fast-dissolving ebastine, 20 mg/ day, in Mexican patients with allergic rhinitis]. / Estudio multicéntrico de satisfacción con ebastina de disolución rápida 20 mg/día en pacientes mexicanos con rinitis alérgica.

BACKGROUND: Allergic rhinitis is an inflammatory disease of the nasal mucosa, with common symptoms, which is essentially characterized by nasal itching, nasal congestion, sneezing, hyaline rhinorrhea and repetitive sneezing. The disease is very common, 15% of the population worldwide suffers it. Among many treatments that have been used to relieve the symptoms of this disease there is a selective inhibitor of H1 receptors, ebastine. OBJECTIVE: To evaluate patient satisfaction using the scale of Treatment Satisfaction Questionnaire for Medication (TSQM). MATERIAL AND METHODS: A multicentric, retrospective, observational study performed in 250 Mexican patients with the diagnosis of intermittent allergic rhinitis (IAR) or persistent allergic rhinitis (PER), confirmed by prick test, specific IgE, or both, treated with lyophilised ebastine in fast-dissolving (FDT) 20 mg at any time in the last two months, prescribed for at least two weeks by their doctor to relieve the symptoms of intermittent allergic rhinitis or persistent allergic rhinitis. We used a validated questionnaire assessment scales, TSQM. RESULTS: The presentation of ebastine fast-dissolving (FDT) is effective and has good tolerability, over 80% of patients reported comfort and satisfaction using it. CONCLUSIONS: Assessment of overall satisfaction, efficacy, tolerability and comfort showed that ebastine in fast-dissolving is an antihistamine with clear benefits to encourage compliance.

Síndrome paraneoplásico en un cáncer de mama / Paraneoplastic syndrome in breast cancer

La dermatomiositis es una miopatía inflamatoria con afectación cutánea que se puede presentar de manera aislada, como un síndrome paraneoplásico (asociada a diferentes tipos de neoplasias) o asociada a conectivopatías. La etiología no está clara y tampoco hay estudios concluyentes en el momento actual de la asociación entre dermatomiositis y cáncer. El síndrome paraneoplásico puede aparecer antes, al mismo tiempo o después de la neoplasia, siendo la relación temporal entre ambas enfermedades difícil de establecer por el pequeño número de casos de los estudios. Presentamos en este artículo un caso de dermatomiositis paraneoplásica. El tumor con el que se relacionaba fue un cáncer de mama cuya presentación coincidió en el tiempo con la dermatomiositis (el diagnóstico se realizó dos meses después de la aparición de la dermatomiositis). El diagnóstico de la neoplasia no se hubiese podido llevar a cabo de no tener un protocolo adecuado para el estudio de la dermatomiositis

Dermatomyositis is an inflammatory myopathy with skin involvement that can occur in an isolated way as a paraneoplastic syndrome (associated to different types of neoplasms) or associated to connective tissue diseases. Its etiology is not clear and there are no conclusive studies at present on the association between dermatomyositis and cancer. The paraneoplastic syndrome may appear before, at the same time, or after the neoplasm, the temporal relationship between both diseases being difficult to establish due to the small number of cases in the studies. In this article, we present a case of paraneoplastic dermatomyositis. The tumor it was related to was a breast cancer whose presentation coincided in time with the dermatomyositis (the diagnosis was made 2 months after the appearance of dermatomyositis). The diagnosis of the neoplasm could not be done as there was no adequate protocol for the study of dermatomyositis

New concepts in cyclosporine pharmacokinetic and dynamic monitoring: the impact of concomitant immunosuppression on target C2 concentrations.

BACKGROUND: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. AIM: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C2 and clarify the impact of concomitant immunosuppression. METHODS: Thirty-eight stable renal transplant recipients were treated with CsA (n=20) or CsA+MMF (n=18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. RESULTS: There were no significant differences in median CsA C2 values and CNa between the CsA alone and the CsA+MMF groups (388 microg/L and 497.5 microg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P<.001). The correlations (r) between C2 and CNa 2h were: CsA r=0.74; CsA+MMF r=0.84 (P<.001 in both cases). CONCLUSIONS: In stable renal transplant patients, median CsA C2 values below 500 microg/L were associated with inhibition of CNa and IL-2 synthesis. CNa and IL-2 production may be good biological markers of CsA immunosuppression. The measurement of CNa depends mainly on CsA concentration, whereas in vitro IL-2 production reflects the effect of both CsA and MMF. Further studies are necessary to define the optimal C2 target concentration and the possible impact of concomitant immunosuppression.

Prevalencia de aabaquismo en adolescentes de uncolegio de bachilleres del estaado de morelos, México

Objetivo: Conocer la prevalencia de tabaquismo entre estudiantes de un Colegio de Bachilleres con la finalidad de contar con información basal para el diseño de una intervención educativa. Material y métodos: Se realizó un estudio transversal con el total de alumnos (n=490) que asistían a una escuela pública urbana en el estado de Morelos, México. Se aplicó un cuestionario, en diciembre de 2001. Como prueba estadística se llevaron a cabo diferencias de proporciones entre grupos a un nivel de confianza del 95%. Resultados: La prevalencia de tabaquismo fue del 27.3%. Los espacios en donde los adolescentes reportaron que han fumado fueron sitios públicos: fiestas (66%), discotecas (43%), y calle (46.6%). Al explorar la relación entre el tabaquismo de los adolescentes y que algún miembro de la familia también fuera adicto al tabaco se encontró un 71.6% (p=0.000). El padre es quien ocupó el primer lugar (55.01%). Entre los estudiantes fumadores el 98.5% consumían además bebidas alcohólicas (p=0.000). Conclusiones: Los datos de esta investigación son semejantes a los reportados entre estudiantes de la India y Australia, pero menores a lo señalado en países europeos (Inglaterra, Noruega) y de América (Estados Unidos, Chile). Los resultados encontrados en este estudio serán utilizados para diseñar una intervención educativa dirigida a disminuir la adicción en esta zona.

Objective: The purpose of this study was to determine the prevalence of smoking in High School students in order to have significant information to design an educative intervention. Material and methods: A transversal exploratory study was performed on 490 students of a public urban Highs School in the State of Morelos, Mexico. A survey was applied in December, 2001. Statistical analysis was done by proportion differences between groups with a confidence level of 95%. Results: Smoking habit prevalence was 27.3%. Teenagers reported to smoke in public places: parties (66%), nightclubs (43%), street (46.6%). The relationship between smoking habits in teenagers and having a relative who is also a tobacco addict was 71.6% (p=0.000). The father held the first place (55.01%). Among smoking teenagers, 98.5% also drank alcoholic beverages (p=0.000). Conclusion: These results are similar to those reported for students in India and Australia, but lower than those for European countries (Great Britain and Norway), and America (USA, Chile). Results of this study will be used to design an educational intervention directed to diminish addiction in this area.

Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C(2).

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.