A. G. González

Antifungal activities of nine traditional Mexican medicinal plants

Eighteen plant extracts from nine traditional Mexican medicinal plants were tested for antifungal activity against two dermatophyte fungal species (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and Annona cherimolia.

Pharmacological Profiles of Acute Myeloid Leukemia Treatments in Patient Samples by Automated Flow Cytometry: A Bridge to Individualized Medicine

BACKGROUND We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models. PATIENTS AND METHODS Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells. RESULTS The sensitivity of single drugs is assessed for standard efficacy (EMAX) and potency (EC50) variables, ranked as percentiles within the population. The sensitivity of drug-combination treatments is assessed for the synergism achieved in each patient sample. We found a large variability among patient samples in the dose-response curves to a single drug or combination treatment. CONCLUSION We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection.

An ex vivo native environment precision medicine test shows high clinical correlation with responses to first line acute myeloid leukemia treatment

P Preventive and Personalized Medicine (PPPM) as the healthcare model of the near future and its tool, i.e., Translational Medicine (TraMed), represent an innovative model of healthcare services to consolidate advanced healthcare and robust platform for relevant branches of predictive diagnostics, personalized therapeutics and preventive drugs. To achieve the implementation of PPPM concept into practice, it is necessary to create a new strategy based upon the sub-clinical recognition of biomarkers long before the disease clinically manifests itself. This strategy would secure preventive measures whose personalization could have a significant influence on demographics! Meanwhile, penetration of new technologies into the market would demand the reforms not only in the area of healthcare but in medical education as well. Therefore, the problem of the preparation of specialists of the newest generation to secure priority in growing up medical doctors as creative artists is becoming particularly urgent and would require significant revision of training programs and curricula of the higher education as applicable to the medical schools. Modernization and integration of widely accepted medical and teaching standards require consolidation of both the life sciences and medicine that may become the conceptual basis for the medical curricula. The main goal of this training is not to achieve advanced training and expansion of technological skills but to provide development of novel multifaceted approaches to build academic schools of the newest generations and to outline curricula and courses to suit markets of the newest medical platforms. PPPM consists of a wide variety of tests and tools including so much complicated areas as networking, mathematic modeling, nanotools and nanotechnologies, cloudy and mobile technologies to suit the requests and standards of the new healthcare model. Coordinated measures to optimize the progress should be well-focused on solving the accumulating problems in healthcare and the concomitant economic burden that societies across the globe are facing more and more. Taking into consideration the current trends and personal experience, we have made first steps towards direct involvement in the modernization of the healthcare model. Guided by the above-mentioned facts, a non-canonical approach has become setting up under the aegis of EPMA (Brussels, EU), PMC (Washington, DC, USA) and ISPM (Tokyo, Japan) a unique team of medical students, young researchers, entrepreneurs in drug designing, clinicians and administrators of the future to come. Used as an educational-methodical kernel is a three-level basic education system (undergraduate, graduate, and postgraduate) to suit the continuing education. Group and individual vectors as part of the basic inventory are represented by translational medicine, bioinformatics, drug design, translational tools, regulatory courses, etc. The model for accelerated development of continuous vocational education (CVE) in PPPM and TraMed is based on the combinatorial approaches (competence, moduletype approach, personal activity, program-design and problem-oriented) to the elucidation of innovative processes of modernization of the existing educational model. The application of the model for development of CVE has required a new type of the infrastructure of the curricula. PPPM whilst secured by the upgraded educational system would offer great and real promise for the future. And the next generations will speak about the XXI century as a time, when healthcare services became predictive and preventive and its outcomes secured and guaranteed!RESULTS Background: We have overcome the limitations of 40 years of ex vivo testing. The aim of this study is to determine the ability of Vivias novel test (based on studying the ex-vivo sensitivity to drugs) to predict the complete remission (CR) rates after induction chemotherapy with cytarabine (Ara-C) and idarubicin (Ida) in 1st line AML.. Material and Methods: This has been an observational clinical trial where bone marrow samples from adult patients diagnosed with de novo AML in Spanish centers from the PETHEMA group were included. Whole marrow samples maintaining their Native Environment were incubated for 48h in well plates containing Ara-C, Ida, or their combination. Pharmacological responses are calculated using population models. Induction response was assessed according to the Cheson criteria (2003). Patients attaining a CR/CRi were classified as responders and the remaining as resistant. Results: 390 patient samples were used to calculate the dose response (DR) curves for Ara-C alone, Ida alone, and their synergism. For clinical correlation we used 142 patients with median 56 years. The strongest clinical predictors were the Area Under the Curve (AUC) of the DR of Ara-C (P=1.34E-05), and the AUC of IDA (P=3.9E-05). The GAM models revealed a significant relationship (RSquare=0.452 and deviance explained=45%) between these predictors and higher probabilities of post-induction resistance. Fig 1A shows a table illustrating the correlation between clinical outcome (columns) and the test predictions (lines). Using the cut off determined by the GAM models. The test obtain a high Specificity and Positive Protective Value (95% and 80,77%) and a lower sensitivity (50%) with a general prediction of a 81,69%. Interestingly, the 5 cases that the test identify as resistant but were clinically sensitive have high level of minimal residual disease. On the other hand, the test does not properly identify 21/142 that are clinically resistant and the test predicts as sensitive (bottom left quadrant right panel). This mismatched subgroup mimics the problems from molecular markers where a resistant clone present in a minority of leukemic cells cannot be detected yet drives the patient response. Consistent with this analysis, adding the cytogenetic risk factor to the ex vivo results, identifying the high risk population by molecular markers that might be present in a minority of the cells, significantly improves the correlation; Fig. 1B shows the 90% overall correlation achieved in 117 patient samples adding the cytogenetic risk factor, with a major improvement in the sensitivity from 50% to 72%. Both approaches lead to substantial improvements in estimated overall survival. ABSTRACT© 2019 The Egyptian Journal of Internal Medicine | Publ Background/purpose of the study Chronic hepatitis C virus (HCV) infection is considered one of the major healthproblems.About170millionpatientswere infectedwithHCVworldwide.Till few years, Egypt was considered the highest HCV prevalent country worldwide, with predominant genotype number 4. The host immunity plays a major role in HCV infection with evolving data confirming the role of T-helper 17 cells in the formation of chronic HCV infection. The aim of our work was to determine the role of interleukins 17A (IL17A), 17F (IL17F) in the formation of chronic hepatitis C infection. Patients and methods We classify the patients into two groups: the first group included 51 chronic HCV patients who did not take antiviral therapy (the study group) and the second group included 51 healthy blood donors (as a control group). The levels of IL17A and IL17F in the serum of both groups were measured using the sandwich enzymelinked immunosorbent assay method. Results The serum values of IL17A were higher in patients with chronic HCV than the other group with the mean values being 52.9±32.6 pg/ml in the patient group and 17.1 ±10.4 pg/ml in the control group. IL17F was slightly higher in the HCV patient group than the control group, but it was statistically insignificant. Moreover, there were significant positive correlations between IL17A and alanine aminotransferase, viral load, and degree of liver fibrosis. Conclusion Patients with chronic HCV infections had a higher serum level of IL17A than the normal persons and it is positively correlated with alanine aminotransferase, viral load, and degree of liver fibrosis. This suggests its pivotal role in the formation of chronic HCV infection; so, it can be used as a new marker for disease progression due to its positive correlation with the severity of liver injury.

1769 – Psychotic disorder and hospitalization through mobile crisis unit

Introduction The utility of Mobile Crisis Unit (MCU) and its target population has been a controversial issue and many scientific articles have been writen about it (1,2). Objective The aim of this study is to identify the demographic and clinical features of patients diagnosed with psychotic disorder who have been hospitalized and have not required hospitalization in psychiatric unit through a Mobile Crisis Unit (MCU). Methods We collected retrospectively demographic and clinical variables. These include psychiatric rating scales of severity: Clinical Global Impression Scale (CGI) and Psychiatric Disease Severity (GEP); of functionality as Global Assessment of Functioning Scale (GAF); the aggressive behaviour and violence scale (AVAT) and psychopathology with the Positive and Negative Syndrome Scale (PANSS) of a total of 136 patients between June 2007 and July 2010. Results There have been found stadisticaly significative differences between patients who have been hospitalized versus patients who have not in the items of treatment adherence and security staff intervention (Table 1). There is a positive correlation between patients who required hospitalization and the clinical scales CGI, GEP, GAF, AVAT, SUMD, PANSS-P and PANSS-G (Table 2). Conclusions We can conclude that patients cared for by the Mobile Crisis Unit (MCU) that require of psychiatric hospitalization have poor adherence to previous treatment. A high frequency of cases require intervention of security staff for having a higher risk of aggressiveness at the moment of hospitalization. The presence of greater psychopathology and functionality severity in patients hospitalized through the Mobile Crisis Unit (MCU) is also considered. Variables No hospitalization Hospitalization p N % N % Sex Men 33 54.1 41 54.7 0.95 Cohabitation Alone 15 24.6 25 33.3 0.27 Toxics Yes 14 23 17 22.7 0.97 Psychiatric history Yes 45 78.9 54 77.1 0.81 Previous hospitalizations Yes 42 68.9 42 56 0.12 Treatment adherence Yes 14 31.1 2 3.5 Security staff Yes 1 1.7 39 57.4 Chi-square Variables No hospitalization Hospitalization p Age 45,3(17,02) 45,44(16,16) 0,96 CGI 4,24(0,82) 5,11(0,67) GEP 12,09(4,18) 15,96(3,82) GAF 47,16(14,21) 37,07 (23,72) AVAT 2,41 (1,98) 4,15 (2,45) SUMD 10,65 (3,29) 12,97 (3,08) PANSS P 22,28(7,02) 28,79(6,43) PANSS N 21,89 (8,44) 20 (8,09) 0,19 PANSS PG 38,8 (9,51) 45,28 (9,65) Mean(SD)–T-test

Cervical spinal cord stimulation for painful spasticity

Aim of investigation: Spinal cord stimulation (SCS) has been shown to be therapeutically effective in disorders of the motor systems. Initially this was demonstrated in DS, spasmodic tortcollis and other degenerative disease. The effectiveness of SCS has increased by the use of variable scs. This study was limited to patients with spasticity and its pain symptoms. Methods: The patients were selected on the basis of being disabled by spasticity and pain. A trial of 14 cases was carried out on 10 males and 4.females-ranging in age from 6 to 46 years. Follow-up ranged from 2 to 18 months. A percutaneous technique was used to place a quadripolar lead epidural at the level of C2-C4 following the determination of the most ideal electrode combination. The system is permanently internalized with a subcutaneously placed receiver. A high frequency stimulation was used and spasticity and pain were checked. Results: In all cases improvement of muscle balance and spasticity were observed and consequently relieved of pain. Conclusions: The percutaneous cervical spinal cord stimulation with a quadripolar lead and high frequency stimulation is a minor procedure and it seems to help this type of motor disorder and its painful side effects.