Medication errors in the care transition of trauma patients.

RATIONALE, AIMS, AND OBJECTIVE: Traumatological patients are vulnerable to medication error given multiple handoffs throughout the hospital since they often require rapid diagnosis and management of multiple concurrent complex conditions. The purpose of this study was to analyze the medication errors (MEs) occurring in the care transition of the traumatological patient. The secondary objectives were to classify the MEs and the level of risk of the pharmacological groups involved. In addition, the causes and contributing factors of those MEs were analyzed. METHODS: An observational, descriptive, and prospective study, spanning 4 months, was performed in a tertiary hospital. All patients admitted to the traumatology service were selected for the study. Data were collected in different locations of the hospital stay: Emergency Service, Resuscitation and Post-Anaesthesia Unit, and Traumatology Hospitalization Unit. In each location, data from the different processes (reconciliation, prescription, validation, dispensing, and administration of medicines) were collected. The medication error (ME) was established as a dependent variable. RESULTS: A total of 31.3% (132) of the patients analyzed showed some ME. The Traumatology Unit was the location where most errors were detected, followed by the Emergency Service. Having analyzed all the locations, it was observed that 64.2% (172) of the MEs were detected in the reconciliation process, 29.5% (79) in the prescription, 3.7% (10) in the dispensing, 1.5% (4) in the administration, and 1.1% (3) in the validation. In terms of risk weighting, the drugs involved in the MEs detected were 53.8% of medium risk, 20.7% of high risk, and 20.3% of low risk. CONCLUSIONS: There is a high prevalence of MEs in the reconciliation process of medication in traumatological patients (64.2%) from our hospital setting. Interestingly, most MEs occurred in this process regardless of the location in the healthcare chain.

Executive summary of the consensus document on the management of perioperative anemia in Spain.

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 8 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from "strongly disagree [1]" to "strongly agree [5]". For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.

Primary care pharmacist-led medication review in older adult patients in coordination with general practitioners: an observational retrospective cohorts study.

Background: Polypharmacy and risk of potentially inappropriate prescribing (PIP) in older adult are being continuously increased. Including a primary care pharmacist (PCP) in the healthcare team is associated with lower rates of medication-related problems (MRPs). Objectives: To determine the impact (in terms of variation of PIP, MRPs and polymedication) of treatment reviews (TR) carried out by the PCP by comparing two cohorts: standard TR vs coordinated TR with prescribing General Practitioners (GP). To assess possible health outcomes in both groups 6 months post-TR. Methods: This is an observational study of two retrospective cohorts (2018 to 2020). All patients who met the inclusion/exclusion criteria were analyzed. Patients ≥65 years, who underwent complete TR by the PCP were included. Patients in a situation of exitus at the time of TR and those who underwent a partial TR were excluded. Control group cohort consisted of patients who underwent standard TR, and intervention group cohort consisted of those who underwent TR coordinated with GP. Sociodemographic, clinical and pharmacological variables were analyzed. Results: 181 patients were enrolled. Mean age 84.4 ± 7.2 years, 78.5% women. Variables (GP-coordinated vs standard TRs) pre-post: decrease in drugs/patient 1.9 (95%CI: 1.4-2.4) vs 0.6 (95%CI: 0.2-1.3), p < 0.05; decrease in MRPs/patient 3.1 (95%CI: 2.8-3.4) vs 1.0 (95%CI: 0.6-1.4), p < 0.05; decrease in PIP/patient 2.0 (95% CI: 1.6-2.2) vs 0.6 (95% CI: 0.2-0.9), p < 0.05. Health outcomes: there was significant difference in average primary-care visits/patient 1.3 ± 0.5 vs 2.2 ± 1.8, p < 0.05. Conclusions: Multidisciplinary interventions between PCP and GP, together with a systematic approach to TR can improve the quality of pharmacotherapy in the elderly. Prospective large follow-up studies are needed to demonstrate a positive trend in health outcomes.

Assessment of the ciliary muscle and scleral anterior thickness in high myopia by optical coherence tomography.

PURPOSE: To assess ciliary muscle (CM) and anterior scleral thickness (AST) dimensions in vivo in high myopia using swept-source optical coherence tomography (SS-OCT) and to compare with emmetropic and hyperopic subjects. METHODS: Cross-sectional study that included 34 high myopic patients (≥ -6 diopters [D]), 90 emmetropes (-1 to +1 D) and 38 hyperopic patients (≥ +3.5 D). CM thickness (CMT) and AST were measured in the temporal and nasal quadrants at 1, 2, and 3 mm from the scleral spur using SS-OCT. In addition, the length of the CM (CML) was evaluated. RESULTS: The dimensions of the CML and the CMT at any of their measurement points were greater in high myopes and emmetropes than in hyperopes, both in the nasal and temporal quadrants (P < .001). However, there were no differences between high myopes and emmetropes for any of the parameters (P ≥ .076) except for the CMT at 3 mm in the temporal quadrant (P < .001). There were no differences in the AST between high myopes, emmetropes and hyperopes, in any of the measurement points or quadrants studied (P > .05). CONCLUSIONS: The SS-OCT allows to measure the CM in vivo, not observing differences in its dimensions between high myopes and emmetropes, but they were smaller in hyperopes. In the measurement of the anterior sclera, no differences were observed between the three groups analyzed according to refraction.

Impact of pharmaceutical validation on prescribing errors in a neonatal intensive care unit. Randomised and controlled study.

Purpose: To compare the frequency of electronic prescription errors when the prescription was validated by the clinical pharmacist vs. when it was not. Methods: This prospective randomised controlled study was conducted in three phases. A randomised phase, in which patients were divided into control and intervention groups, and a pre- and post-intervention phase were consecutively performed to analyse the impact of pharmaceutical validation of prescriptions in a neonatal intensive care unit (NICU). This study was performed at a highly complex NICU at a tertiary hospital. All patients born during the study period who were admitted to the NICU, with a stay lasting ≥24 h, and received active pharmacological treatment were included in the study. Pharmaceutical validation was performed according to the paediatric pharmaceutical care model. A high level of validation was selected for this study. In the intervention group, discrepancies found during the review process were communicated to the medical team responsible for the patients and resolved on the same day. Results: In total, 240 patients were included in this study. Sixty-two patients were allocated to the pre-intervention (n = 38) or post-intervention (n = 24) groups, and 178 patients were randomly sorted into two groups, control (n = 82 newborns) and intervention (n = 96 newborns). During the randomisation phase, the number of prescription errors detected was significantly lower in the intervention group than that in the control group (129 vs. 270; p < 0.001). Similarly, prescription errors reaching the patient were significantly reduced from 40% (n = 108) in the control group to 1.6% (n = 2) in the intervention group. In the pre- and post-intervention periods, the prescription lines containing prescription errors decreased from 3.4% to 1.5% (p = 0.005). Conclusions: This study showed that the pharmaceutical validation process decreased both the number of errors in the electronic prescribing tools and the number of prescription errors reaching the patient.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program. / Recomendaciones de la Sociedad Española de Cirugía Torácica y de la Sección de Cardiotorácica y Cirugía Vascular de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor, para los pacientes sometidos a cirugía pulmonar incluidos en un programa de recuperación intensificada.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyses, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Maraviroc in treatment-experienced patients with HIV-1 infection - experience from routine clinical practice.

OBJECTIVE: Few data are available about the efficacy of maraviroc (MVC) during routine use. We characterized indications for MVC use and the efficacy of MVC in clinical practice. METHODS: Thirty-two patients treated with MVC at our institution between 2006 and 2009 were included. Genotypic (n +/- 31) and phenotypic (n +/- 13) tropism analysis was performed. We determined indications for MVC use, characteristics of antiretroviral combination partners and treatment outcome. RESULTS: Complete suppression of viral replication was achieved in 78% after 6 months. A median increase of 124 CD4+ cells/microl after 6 months was observed. Concordance between phenotypic and genotypic tropism was found in 75%. Indications for MVC treatment included treatment failure (n +/- 15), intolerance to previous antiretrovirals (n +/- 6) and add-on MVC for intensification without changing the current regimen (n +/- 11). The add-on strategy was used in patients with a relatively low viremia in order to achieve complete viral load suppression or in situations with suppressed viral load but judged as unstable due to an extensive resistance pattern. Salvage drugs most frequently combined with MVC were darunavir (n +/- 14) and raltegravir (n +/- 14). - The genotypic assay had predicted CXCR4 tropism in 5 patients, using a false positive rate (FPR) of 20%. Lowering the FPR to 5% predicted CCR5 tropism in 4 cases, still resulting in sustained complete viral response under MVC use. CONCLUSIONS: MVC containing salvage regimens achieve relevant CD4 cell increases and high viral response rates. In patients with few remaining treatment options it may be justified to lower the FPR-cutoff to 5% when predicting the coreceptor usage. Hereby, MVC could still be applied in selected patients with otherwise limited treatment options.

Resumen ejecutivo del documento de consenso sobre el manejo de la anemia perioperatoria en España / Executive summary of the consensus document on the management of perioperative anemia in Spain

La anemia perioperatoria constituye un factor independiente de riesgo de morbimortalidad posoperatoria. Sin embargo, persisten barreras conceptuales, logísticas y administrativas que dificultan la implementación generalizada de protocolos para su manejo. El coordinador del proyecto convocó a un grupo multidisciplinar de ocho profesionales para elaborar un documento de consenso sobre el manejo de la anemia perioperatoria, con base a en serie puntos claves (PCs) relativos a su prevalencia, consecuencias, diagnóstico y tratamiento. Estos PCs fueron evaluados utilizando una escala Likert de 5 puntos, desde «totalmente en desacuerdo [1]» a «totalmente de acuerdo [5]». Cada PC se consideró consensuado si recibía una puntuación de 4 o 5 por al menos siete participantes (> 75%). A partir de los 36 PCs consensuados, se construyeron algoritmos diagnóstico-terapéuticos que pueden facilitar la implementación de programas de identificación precoz y manejo adecuado de la anemia perioperatoria, adaptados a las características de las instituciones hospitalarias de nuestro país.(AU)

Perioperative anemia is an independent risk factor for postoperative morbidity and mortality. However, conceptual, logistical and administrative barriers persist that hinder the widespread implementation of protocols for their management. The project coordinator convened a multidisciplinary group of 9 experienced professionals to develop perioperative anemia management algorithms, based on a series of key points (KPs) related to its prevalence, consequences, diagnosis and treatment. These KPs were assessed using a 5-point Likert scale, from “strongly disagree [1]” to “strongly agree [5]”. For each KP, consensus was reached when receiving a score of 4 or 5 from at least 7 participants (>75%). Based on the 36 KPs agreed upon, diagnostic-therapeutic algorithms were developed that we believe can facilitate the implementation of programs for early identification and adequate management of perioperative anemia, adapted to the characteristics of the different institutions in our country.(AU)

Ecchymosis and/or haematoma formation after prophylactic administration of subcutaneous enoxaparin in the abdomen or arm of the critically ill patient. / Formación de equimosis y/o hematoma tras la administración profiláctica de enoxaparina subcutánea en abdomen o brazo en pacientes críticos.

INTRODUCTION: Ecchymosis and/or haematoma are the most common adverse events after subcutaneous administration of low molecular weight heparin. There is no strong recommendation as to the puncture site. OBJECTIVE: To evaluate the adverse events, ecchymosis and/or haematoma after the administration of prophylactic subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient. METHODOLOGY: A randomised, two-arm clinical trial (injection in the abdomen vs the arm), performed between July 2014 and January 2017, in an 18-bed, polyvalent intensive care unit. Patients receiving prophylactic enoxaparin, admitted >72h, with no liver or haematological disorders, a body mass index (BMI) >18.5, not pregnant, of legal age and with no skin lesions which would impede assessment were included. We excluded patients who died or who were transferred to another hospital before completing the evaluation. We gathered demographic and clinical variables, and the onset of ecchymosis and/or haematomas at the injection site after 12, 24, 48 and 72hours. A descriptive analysis was undertaken, with group comparison and logistic regression. The study was approved by the ethics committee with the signed consent of patients/families. RESULTS: 301 cases (11 excluded): 149 were injected in the abdomen vs 141 in the arm. There were no significant differences in demographic and clinical variables, BMI, enoxaparin dose or antiplatelet administration [ecchymosis, abdomen vs arm, n(%): 66(44) vs 72(51), P=.25] [haematoma abdomen vs arm, n(%): 9(6) vs 14(10), P=.2]. Statistical significance was found in the size of the haematomas after 72h: [area of haematoma (mm2) abdomen vs arm, median (IQR): 2(1-5.25) vs 20(5.25-156), P=.027]. CONCLUSIONS: In our patient cohort, prophylactic subcutaneous enoxaparin administered in the abdomen causes fewer haematomas after 72hours, than when administered in the arm. The incidence rate of ecchymosis and haematoma was lower than the published incidence in critically ill patients, although patients receiving anti-platelet agents present a higher risk of injury. No relationship was observed in relation to BMI.

Alteration of mammalian cells by interaction with artificial lipid vesicles.

Artificial lipid vesicles interact with a variety of mammalian cells, including blood cells, spleen cells, and tumor cells, and during this interaction components can be transferred from the vesicle to the cell and from the cell to the vesicle. Transfer of intravesicular material is observed when artificial lipid vesicles carrying an intravesicular marker, 99mTc (as TcO4- ion), are incubated with mammalian cells. When vesicles prepared with [14C] phospholipid are incubated with mammalian cells, the labeled lipid is also transferable to mammalian cells. Conversely, if the mammalian cell surface is radiolabeled (with 125I), the cell marker is in part transferable to the vesicles. Thus, interaction of mammalian cells with vesicles alters the characteristics of the cell in several ways. There is a loss of some cell surface components, a gain of vesicle lipid components, and an acquisition of intravesicular contents. Such alteration may affect the biological behavior of the cell in vivo. Thus, the in vivo distribution in the mouse of isologous red blood cells is altered after interaction with vesicles; the liver and spleen remove large proportions of such cells in comparison to control erythrocytes labeled with 51Cr. The behavior of vesicle survivors from a cell interaction is also altered. Upon reexposure of such vesicles to a fresh population of cells, the intravesicular marker is no longer transferable to cells; and upon injection of such vesicles into mice, the liver accumulation of vesicular label is reduced as compared with that of nonincubated vesicles.

Vesicle interactions with polyamino acids and antibody: in vitro and in vivo studies.

Artificial spherules or vesicles of 900 A in diameter formed from phosphatidylcholine and gangliosides and enclosing 99mTcO4 - (standard preparation) survive intact in the circulation of the mouse. Polyamino acids and protein have been incorporated into and onto the vesicles; such vesicles remain intact as determined by diffusion dialysis studies and by electron paramagnetic resonance studies of vesicles enclosing spin label. In studying the distribution of polyamino acid-vesicles and protein vesicles in vivo, it was found that the latter distribute differently from standard vesicles or free protein alone whereas aromatic polyamino acid-vesicles concentrate in the liver and spleen to a greater extent than standard vesicles. We conclude that the permeability and stability characteristics of vesicles may be preserved when they are modified by the addition of protein or polyamino acids and that such modification of vesicles may be associated with an alteration of their fate in vivo. The potential exists to use vesicles as carriers of radiopharmaceuticals and other drugs and to direct the vesicles preferentially to tissue targets in vivo.

Reversal of cytosine arabinoside (ara-C) resistance by the synergistic combination of 6-thioguanine plus ara-C plus PEG-asparaginase (TGAP) in human leukemia lines lacking or expressing p53 protein.

BACKGROUND: Sequence-specific combinations of purine analogs, such as fludarabine or 6-mercaptopurine (6-MP), administered prior to cytosine arabinoside (ara-C) have been shown to abrogate ara-C resistance in human leukemia cells in vitro and in patients with relapsed acute myeloid or lymphoblastic leukemias. The two-drug combination of 6-MP plus ara-C results in greater cytotoxicity than that achieved with either ara-C or 6-MP alone. Further preclinical investigations have shown that the addition of PEG-asparaginase (PEG-ASNase) to the combination of 6-MP plus ara-C (6-MP + ara-C + PEG-ASNase) results in 15.6-fold synergism over that achieved with the two-drug regimen. This is due to increased DNA damage leading to apoptotic cell death. PURPOSE: Since the intravenous preparation of 6-MP is no longer available and since oral 6-thioguanine (6-TG) provides higher levels of intracellular thioguanine nucleotides than an isotoxic dose of oral 6-MP, we investigated the potential drug synergism of 6-TG plus ara-C plus PEG-ASNase (TGAP) in myeloid (HL60/S, HL60/SN3, U937) and lymphoblastic (CEM/0, CEM/ ara-C/B, CEM/ara-C/I, MOLT-4) leukemia cell lines. The CEM clones, MOLT-4 and HL60/SN3 cell lines expressed functional or measurable p53 protein, while the other cell lines did not. METHODS: The MTT and trypan blue dye exclusion assays were used to determine drug cytotoxicity. In addition, cellular apoptosis and cellular p53, p21/waf-1 and bcl-2 protein concentrations were determined by FACS analysis and ELISA assays. RESULTS: Sequential exposure to 6-TG (24 h) plus ara-C (24 h) plus PEG-ASNase (24 h) produced 1.3- to 18.3-fold drug synergism over the two-drug combination of 6-TG plus ara-C. The molecular mechanism of synergism was due to the fact that the three-drug combination was capable of downregulating bcl-2 oncoprotein levels in these cell lines even when p53 was absent. CONCLUSION: These studies strongly demonstrate that the TGAP regimen is highly synergistic in p53-null and p53-expressing leukemia cell lines. We conclude that this combination regimen is collaterally sensitive with ara-C and further evaluation in an investigational phase I trial in relapsed leukemia patients is warranted.

Development of a double-drug-resistant human leukemia model to cytosine arabinoside and L-asparaginase: evaluation of cross-resistance to other treatment modalities.

We have developed an in vitro model of 38 T-lymphoblastic leukemia lines resistant to cytosine arabinoside (ara-C) and L-asparaginase (ASNase). Of these, 26 cell lines resistant to both drugs, 6 resistant to ara-C, and 6 resistant to ASNase were isolated. In 18 of these cell lines, all randomly selected, resistance to ara-C, ASNase and gamma radiation was documented by the MTT and trypan blue assays, as well as flow cytometry with Annexin V and propidium iodide (PI) staining. In these lines, p53, p21WAF1, and bcl-2 levels were measured by ELISA. Results show that P21WAF1 upregulation following p53 induction did not occur, suggesting that p53 function may be lost. Moreover, the data imply that upregulation of bcl-2 is critical in the development of resistance to ara-C and ASNase in these leukemic lines. In the CEM/0 parent line, p53 maintained its ability to interact with its DNA binding site as documented by the electrophoretic mobility shift assay (EMSA). But in one single- and one double-resistant leukemic cell line examined, p53 was not shown to maintain this ability. We conclude that double-resistant clones to ara-C and ASNase are refractory to both drugs, providing an excellent leukemic model to investigate the multiple-drug resistance.

Cytosine arabinoside (ara-C) resistance confers cross-resistance or collateral sensitivity to other classes of anti-leukemic drugs.

The major limitation of treatment with antimetabolite drugs is that they produce resistant clones both in vitro and in patients who either do not respond to treatment or relapse soon after response has been documented. To better understand the phenomenon of cross-resistance, we developed seven CEM/ara-C-resistant leukemic clones from the CEM/0 (wt) cell line. These clones ranged from 4- to 3.5 x 10(8)-fold more resistant to ara-C than the wt CEM/0 cell line. Using this model, we determined IC50 concentrations to several chemotherapeutic agents and gamma radiation, and we also studied pro- (p53) and anti-apoptotic (bcl-2) proteins, as well as P-glycoprotein (P-gp) and multidrug resistance related protein (MRP). The cell viability assays showed that these clones were cross-resistant to 6-thioguanine (6-TG) or 6-mercaptoguanosine (6-TGuo) from 1.1- to 8.8-fold with ara-C; cross-resistance to vincristine (VCR) was from 200- to 1 x 10(4)-fold with ara-C. Taxotere (TXR) showed cross-resistance with ara-C from 1.39- to 3.03 x 10(3)-fold; dexamethasone (DEX) also showed a significant degree of cross-resistance from 27.4- to 3.87 x 10(7)-fold. Gamma radiation treatments from 0.77 Gy to 12.3 Gy showed a radiation dose-dependent cross-resistance with ara-C from 1.43- to 2.93-fold. Idarubicin was collaterally sensitive with ara-C from 4.6- to 1 x 10(9)-fold in these cell lines. The CEM/ara-C/G resistant cell line was 3-fold more sensitive to 6-TG or VCR than CEM/0 (wt), and 5-fold more sensitive to 6-TGuo. This cell clone expressed p53 and did not overexpress bcl-2 protein. All of the cell lines studied, CEM/0 (wt) and the ara-C resistant clones, showed functional p53 protein. The cell treatment with 0.1, 1 and 10 microM ara-C for 48 hours showed increased p53 protein expression in most of these lines. No increase in bcl-2 protein expression was seen in the wt cell line after ara-C treatment for 48 hours. Three cell lines resistant to ara-C (CEM/ara-C/B, CEM/ara-C/D and CEM/ara-C/I) showed an important increased expression of bcl-2 protein after treatment with 1 microM ara-C, but not after 10 microM. This alteration may lead to resistance to apoptosis and enhanced cell survival. The ratio of bcl-2 to p53 was increased significantly in these three clones, thus favoring an anti-apoptotic drive. All of the cell lines examined were negative for MRP expression and only two, CEM/ara-C/B and CEM/ara-C/J, were positive for MRP functional activity. However, three ara-C resistant cell clones, CEM/ara-C/7A, CEM/ara-C/B and CEM/ara-C/G, were positive for P-gp expression and functional activity. It is apparent that selection for ara-C resistance confers cross-resistance to many other classes of drugs and gamma radiation, probably due to bcl-2 protein overexpression or P-gp and MRP expression, as independent mechanisms.

Vaginal misoprostol 1000 microg for early abortion.

The objective of this study was to evaluate the safety and efficacy of 1000 microg misoprostol vaginally (Cytotec) self-administered into the vagina for medical abortion. Three-hundred women with gestations between 42 and 63 days, with previous written consent, received vaginal misoprostol every 24 h up to a maximum of three doses for abortion. Outcome measures assessed included: successful abortion (complete abortion without surgery), side effects, decrease in hemoglobin, mean time of vaginal bleeding, mean expulsion time and mean time of returning of menses. Complete abortion occurred in 279/300 (93.0%, 95% CI 90, 96) patients. Medication to relieve symptoms was administered to all subjects after every misoprostol dose. Vaginal bleeding lasted 14.7 +/- 5.4 days. Mean expulsion time was 8.1 +/- 3.0 h for those who aborted after the first misoprostol dose. The mean drop in hemoglobin was statistically significant (p = 0.0001) but without clinical relevance. The frequencies of nausea and diarrhea were high. According to the observed outcomes, 1000-microg misoprostol vaginally could be a valid method to terminate pregnancies up to nine weeks gestation.

Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment.

Fraxetin belongs to an extensive group of natural phenolic antioxidants. We have investigated the modifications in endogenous antioxidant capacity; superoxide dismutase (SOD), catalase (CAT), total and selenium-dependent glutathione peroxidases (GPx) and glutathione reductase (GR) and stress index; glutathione disulphide (GSSG)/reduced glutathione (GSH) ratio and thiobarbituric acid-reactive substances (TBARs) in liver and brain supernatants of C57BL/6J male 12-month-old mice under fraxetin treatment for 30 days. Liver SOD and GPx (total and Se-dependent) activities were not significantly affected by fraxetin, whereas they were increased in the brain compared with control animals. GR activity increased significantly only in the liver of treated mice. Fraxetin treatment-related decreases were shown for GSSG/GSH ratio and rate of accumulation of TBARs (not significant in TBARs) in both tissues. We concluded that the net effect of fraxetin treatment on endogenous antioxidant capacity suggests that this compound might provide an important resistance to, or protection against, free-radical-mediated events which contribute to degenerative diseases of ageing.

Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes.

The purpose of this study was to investigate possible protective effects of ursolic acid against CCl4-induced alterations of antioxidant defence enzymes in vivo as well as its effects against CCl4-intoxication in vitro. Pre-treatment of rats with ursolic acid significantly reduced serum levels of glutamate-oxalate-transaminase and glutamate-pyruvate-transaminase previously increased by administration of CCl4. Treatment with ursolic acid also significantly reversed the decreased superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase activities and glutathione levels in the liver, as the concentration of reduced glutathione was increased and the content of oxidized glutathione decreased in ursolic acid treated groups. Levels of lipid peroxidation were higher in the CCl4 group but the increase was also reduced after drug treatment (p < 0.01 for 1, 2.5 and 5 mmol/kg). In vitro results indicated that addition to the culture medium of ursolic acid (p < 0.01 for 500 microM) resulted in a reduction of glutamate-oxalate-transaminase, lactate dehydrogenase activities and in a good survival rate for the CCl4-intoxicated hepatocytes. Ursolic acid also ameliorated lipid peroxidation in primary cultured rat hepatocytes exposed to CCl4, as demonstrated by a reduction in malondialdehyde production. Moreover, ursolic acid (50-500 microM) showed radical scavenging properties in terms of hydroxyl formation. The results obtained suggest that ursolic acid treatment can normalize the disturbed antioxidant status of rats intoxicated with CCl4 by maintaining the levels of glutathione and by inhibiting the production of malondialdehyde due to its radical scavenging properties.

Dental management of the chronic vomiting patient.

A review of dental erosion secondary to medical or psychologic causes (or both) has been presented. Clinical signs and symptoms and appropriate restorative therapy have been discussed. Diagnosis and stabilization of the chronic vomiting patient must precede definitive restorative procedures.

Surgical management for snoring and sleep apnea.

Obstructive sleep apnea is a serious medical problem producing both physical and behavioral derangement. It is essential to provide a thorough workup and evaluation of all patients seeking care for snoring or OSA. Polysomnography is the standard for evaluation and assessment of the severity of OSA in every patient. The evaluation and workup for surgical intervention should include a thorough history, complete head and neck evaluation, nasopharyngeal laryngoscopy with a flexible fiberoptic endoscope, and appropriate imaging (e.g., cephalometrics). This workup allows pathologic entities of the upper airway (e.g., neoplasia, cysts) to be ruled out and regions of disproportionate anatomy (e.g., large soft palate, uvula, base of tongue, and a hypoplastic mandible) to be documented. Treatment of site-specific based on the finding of the evaluation. Treatment of snoring is often addressed by more conservative palatal procedures such as LAUP, RVTR, or electrocautery of the soft palate. The more aggressive palatal procedures such as UPPP are generally reserved for OSA. Nasal airway reconstruction may aid in the treatment of OSA, because increased nasal resistance and obstruction may significantly increase the negative pressure of the upper airway, leading to collapse of the velopharyngeal, base-of-tongue, and hypopharyngeal regions. Children with OSA usually respond well to adenotonsillectomy. Occasionally, uvulopalatopharyngeal procedures may be necessary. Craniofacial anomalies and significant skeletal anomalies such as severe mandibular hypoplasia have historically been problematic. Tracheostomies were at one time the only way to secure the airway in these patients. New developments in distraction osteogenesis have enabled mandibular lengthening and airway improvement, leading to earlier decannulation of these patients. The combined phase I and phase II treatment has a success rate of greater than 90%. Phase I treatment may include nasal reconstruction, uvulopalatopharyngeal, base-of-tongue, and hypopharyngeal surgery. Phase I surgery has a documented success rate of about 70% to 80%. Phase II surgery (MMA) has a success rate approaching 100%. In certain cases, MMA may be used as the primary treatment of OSA.