RESUMEN
Most of pharmaceutical agents display a number of biological activities. It is obvious that testing even one compound for thousands of biological activities is not practically possible. A computer-aided prediction is therefore the method of choice in this case to select the most promising bioassays for particular compounds. Using the PASS Online software, we determined the probable anti-inflammatory action of the 12 new hybrid dithioloquinolinethiones derivatives. Chemical similarity search in the World-Wide Approved Drugs (WWAD) and DrugBank databases did not reveal close structural analogues with the anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in the carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds (2a, 3a-3k except for 3j) varied between 52.97% and 68.74%, being higher than the reference drug indomethacin (47%). The most active compounds appeared to be 3h (68.74%), 3k (66.91%) and 3b (63.74%) followed by 3e (61.50%). Thus, based on the in silico predictions a novel class of anti-inflammatory agents was discovered.
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Antiinflamatorios , Carragenina , Relación Estructura-Actividad Cuantitativa , Quinolinas , Animales , Ratones , Antiinflamatorios/química , Antiinflamatorios/farmacología , Quinolinas/química , Quinolinas/farmacología , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Tionas/química , Tionas/farmacología , Masculino , Edema/tratamiento farmacológico , Edema/inducido químicamenteRESUMEN
Most of pharmaceutical agents display several or even many biological activities. It is obvious that testing even one compound for thousands of biological activities is a practically not reasonable task. Therefore, computer-aided prediction is the method of choice for the selection of the most promising bioassays for particular compounds. Using PASS Online software, we determined the probable antimicrobial activity of the 31 steroid derivatives. Experimental testing of the antimicrobial activity of the tested compounds by microdilution method confirmed the computational predictions. Furthermore, P. aeruginosa and C. albicans biofilm formation was investigated. Compound 11 showed a biofilm reduction by 42.26% at the MIC of the tested compound. The percentages are lower than ketoconazole, but very close to its activity.
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Antiinfecciosos , Antifúngicos , Simulación del Acoplamiento Molecular , Antifúngicos/farmacología , Relación Estructura-Actividad , Antibacterianos/farmacología , Hidrazonas/farmacología , Relación Estructura-Actividad Cuantitativa , Antiinfecciosos/farmacología , Candida albicans , Esteroides/farmacología , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Nine new functionally substituted derivatives of 2-aminothiazole were evaluated for antimicrobial activity using microdilution method against the panel of eight bacterial and eight fungal strains. Evaluation of antibacterial activity revealed that compounds are potent antibacterial agents, more active than ampicillin and streptomycin except of some compounds against B. cereus and En. cloacae. The best compound appeared to be compound 8. The most sensitive bacteria appeared to be En. cloacae, while L. monocytogenes was the most resistant. Compounds also exhibited good antifungal activity much better than two reference drugs, ketoconazole and bifonazole. Compound 1 exhibited the best antifungal activity. The most sensitive fungus was T. viride, while A. fumigatus was the most resistant. Bacteria as well as fungi in general showed different sensitivity towards compounds tested. Molecular docking studies revealed that MurB inhibition is probably involved in the mechanism of antibacterial activity, while CYP51 of C. albicans is responsible for the mechanism of antifungal activity. Finally, it should be mentioned that all compounds displayed very good druglikeness scores.
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Antiinfecciosos , Antifúngicos , Antifúngicos/farmacología , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad Cuantitativa , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Hongos , Bacterias , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Despite the greatest achievement in the development of anti-inflammatory agents in the last two decades, the current clinical drugs suffer from a variety of complications in community settings and hospital. There is still an urgent need to design novel molecules with better safety profile and with different molecular targets from those in current clinical use. The aim of this research was to discover a series of benzothiazole-based thiazolidinones with lipoxygenase (LOX) inhibitory activity as a mechanism of anti-inflammatory action. Carrageenan-induced mouse foot paw oedema assay was carried out to determine the anti-inflammatory activity, while LOX inhibition was examined through the conversion of sodium linoleate to 13-hydroperoxylinoleic acid. Molecular docking studies were performed using AutoDock 4.2 software. The anti-inflammatory activity of the title compounds was determined in a range of 18.4%-69.57%, where compound #3 was found to be the most potent (69.57%) and also to be more active than the reference drug indomethacin (47%). Moreover, compound #3 showed the highest LOX inhibitory activity with IC50 of 13 µM being less potent to that of the reference NDGA (IC50 = 1.3 µM). Compound #3 has been identified as lead compound for further modification in an attempt to improve anti-inflammatory and LOX inhibitory activities.
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Inhibidores de la Lipooxigenasa , Lipooxigenasa , Animales , Antiinflamatorios/farmacología , Antiinflamatorios no Esteroideos/farmacología , Benzotiazoles/farmacología , Edema/inducido químicamente , Edema/tratamiento farmacológico , Lipooxigenasa/uso terapéutico , Inhibidores de la Lipooxigenasa/farmacología , Ratones , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad Cuantitativa , Glycine max , Relación Estructura-ActividadRESUMEN
Herein we report the evaluation of the antimicrobial activity of some previously synthesized 3-(3,4-dihydroxyphenyl)glyceric acid in benzylated and in free 3,4 hydroxy groups in catechol moiety along with some caffeic and 3-(3,4-dihydroxyphenyl)glyceric acid amides using the microdilution method. The evaluation revealed that compounds showed in general moderate to low activity with MIC in range of 0.36-4.5 mg/mL. Compounds were also studied against three resistant bacteria strains MRSA (Methicillin-resistant Staphylococcus aureus), E. coli and P. aeruginosa. Seven out of ten compounds were more potent than reference drugs ampicillin and streptomycin against MRSA, while against another two resistant strains seven compounds showed low activity and the rest were inactive. Antifungal activity of the tested compounds was much better than antibacterial, with MIC in the range of 0.019-3.0 mg/mL. Compounds #7 and 15 showed good activity against all fungi tested, being more potent than ketoconazole and in some case even better than bifonazole used as reference drugs. Docking studies revealed that the most active compound #7 binds to the haem group of the enzyme in the same way as ketoconazole.
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Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Antibacterianos/farmacología , Escherichia coli , Ácidos Glicéricos , Cetoconazol , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad Cuantitativa , Relación Estructura-ActividadRESUMEN
Griseofulvin is a well-known antifungal drug that was launched in 1962 by Merck & Co. for the treatment of dermatophyte infections. However, according to predictions using the Way2Drug computational drug repurposing platform, it may also have antibacterial activity. As no confirmation of this prediction was found in the published literature, this study estimated in-silico antibacterial activity for 42 griseofulvin derivatives. Antibacterial activity was predicted for 33 of the 42 compounds, which led to the conclusion that this activity might be considered as typical for this chemical series. Therefore, experimental testing of antibacterial activity was performed on a panel of Gram-positive and Gram-negative micro-organisms. Antibacterial activity was evaluated using the microdilution method detecting the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). The tested compounds exhibited potent antibacterial activity against all the studied bacteria, with MIC and MBC values ranging from 0.0037 to 0.04 mg/mL and from 0.01 to 0.16 mg/mL, respectively. Activity was 2.5-12 times greater than that of ampicillin and 2-8 times greater than that of streptomycin, which were used as the reference drugs. Similarity analysis for all 42 compounds with the (approximately) 470,000 drug-like compounds indexed in the Clarivate Analytics Integrity database confirmed the significant novelty of the antibacterial activity for the compounds from this chemical class. Therefore, this study demonstrated that by using computer-aided prediction of biological activity spectra for a particular chemical series, it is possible to identify typical biological activities which may be used for discovery of new applications (e.g. drug repurposing).
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Antibacterianos/farmacología , Reposicionamiento de Medicamentos , Griseofulvina/farmacología , Antibacterianos/química , Antifúngicos/química , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Griseofulvina/análogos & derivados , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) remain the most promising anti-AIDS agents that target the HIV-1 reverse transcriptase enzyme (RT). However, the efficiency of approved NNRTI drugs has decreased by the appearance of drug-resistant viruses and side effects upon long-term usage. Thus, there is an urgent need for developing new, potent NNRTIs with broad spectrum against HIV-1 virus and with improved properties. In this study, a series of thiazolidinone derivatives was designed based on a butterfly mimicking scaffold consisting of a substituted benzothiazolyl moiety connected with a substituted phenyl ring via a thiazolidinone moiety. The most promising derivatives were selected using molecular docking analysis and PASS prediction program, synthesized and evaluated for HIV-1 RT inhibition. Five out of fifteen tested compounds exhibited good inhibitory action. It was observed that the presence of Cl or CN substituents at the position 6 of the benzothiazole ring in combination with two fluoro atoms at the ortho-positions or a hydrogen acceptor substituent at the 4-position of the phenyl ring are favourable for the HIV RT inhibitory activity.
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Diseño de Fármacos , Transcriptasa Inversa del VIH/antagonistas & inhibidores , VIH-1/efectos de los fármacos , Simulación del Acoplamiento Molecular , Inhibidores de la Transcriptasa Inversa/síntesis química , Inhibidores de la Transcriptasa Inversa/farmacología , Relación Estructura-ActividadRESUMEN
Herein we report the design, synthesis, molecular docking study and evaluation of antimicrobial activity of ten new dithioloquinolinethiones. The structures of compounds were confirmed by 1H NMR, 13C NMR and HPLC-HRMS. Before evaluation of their possible antimicrobial activity prediction of toxicity was performed. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. All compounds appeared to be more active than ampicillin and almost all than streptomycin. The best antibacterial activity was observed for compound 8c 4,4,8-trimethyl-5-{[(4-phenyl-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)thio]acetyl}-4,5-dihydro-1H-[1,2]dithiolo[3,4c]quino lone-1-thione). The most sensitive bacterium En.cloacae followed by S. aureus, while L.monocytogenes was the most resistant. All compounds were tested for antifungal activity also against eight fungal species. The best activity was expressed by compound 8d (5-[(4,5-Dihydro-1,3-thiazol-2-ylthio)acetyl]-4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione). The most sensitive fungal was T. viride, while P. verrucosum var. cyclopium was the most resistant one. All compounds were more potent as antifungal agent than reference compound bifonazole and ketoconazole. The docking studies indicated a probable involvement of E. coli DNA GyrB inhibition in the anti-bacterial mechanism, while CYP51ca inhibition is probably responsible for antifungal activity of tested compounds. It is interesting to mention that docking results coincides with experimental.
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Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Quinolinas/química , Quinolinas/farmacología , Antibacterianos/síntesis química , Antifúngicos/síntesis química , Espectroscopía de Resonancia Magnética con Carbono-13 , Cromatografía Líquida de Alta Presión , Diseño de Fármacos , Hongos/clasificación , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Espectroscopía de Protones por Resonancia Magnética , Quinolinas/síntesis química , Relación Estructura-ActividadRESUMEN
Docking analysis was used to predict the effectiveness of adamantanyl insertion in improving cycloxygenase/lipoxygenase (COX/LOX) inhibitory action of previously tested 2-thiazolylimino-5-arylidene-4-thiazolidinones. The crystal structure data of human 5-LOX (3O8Y), ovine COX-1 (1EQH) and mouse COX-2 (3ln1) were used for docking analysis. All docking calculations were carried out using AutoDock 4.2 software. Following prediction results, 11 adamantanyl derivatives were synthesized and evaluated for biological action. Prediction evaluations correlated well with experimental biological results. Comparison of the novel adamantanyl derivatives with the 2-thiazolylimino-5-arylidene-4-thiazolidinones previously tested showed that insertion of the adamantanyl group led to the production of more potent COX-1 inhibitors, as well as LOX inhibitors (increased activity from 200% to 560%). Five compounds out of the 11 exhibited better activity than naproxen; while nine out of 11 showed better activity than NDGA and seven compounds possessed better anti-inflammatory activity than indomethacin.
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Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Diseño de Fármacos , Simulación del Acoplamiento Molecular , Tiazolidinas/química , Tiazolidinas/farmacología , Animales , Araquidonato 5-Lipooxigenasa/metabolismo , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Inhibidores de la Ciclooxigenasa/farmacología , Activación Enzimática/efectos de los fármacos , Humanos , Inhibidores de la Lipooxigenasa/farmacología , Ratones , Ovinos , Relación Estructura-ActividadRESUMEN
BACKGROUND: Before applying new blood management strategies, the extent of blood product transfusions and its correlation with perioperative mortality should be identified. METHODS: This study retrospectively analyzed the extent of perioperative transfusions of red blood cells (RBC), fresh frozen plasma (FFP), and platelets (PLT) in 565 consecutive cardiac surgery patients, who received transfusions based on standard prescriptions. Patients were stratified in four groups according to perioperative transfusion units (no transfusion, <5, 5-10, >10 units). Mortality was analyzed in relation to the type and extent of each blood product transfused and their combinations. Subsequently, the ability of transfusion volume to predict mortality was tested. RESULTS: Most patients received blood product transfusions perioperatively. The observed mortality (11.7 %) correlated significantly with the volume of transfusion. Patients transfused with >5 RBC or FFP units or >10 PLT units had increased mortality compared with those receiving fewer transfusions (23.9 % vs 4.5 %, 27.4 % vs 6 %, 24.5 % vs 8.5 %, p <0.05, respectively). Analysis revealed that cutoffs of >5 units of RBC or >15 units of RBC, FFP, and PLT additively (sensitivity: 74.2 % and 72.7 %, specificity: 68.7 % and 69.5 %, respectively) had an acceptable discrimination ability for perioperative mortality (Area under the ROC curve: 0.756, p <0.001, and 0.735, p <0.001, respectively). CONCLUSIONS: This study confirmed a dose-dependent, transfusion-associated, increased mortality in cardiac surgery patients who received standard prescription transfusions. The results support the need for applying validated, patient-specific blood conservation strategies that correspond to the patient's actual perioperative transfusion needs. HIPPOKRATIA 2018, 22(2): 68-74.
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BACKGROUND: Severe or massive bleeding in cardiac surgery is an uncommon but important clinical scenario. Its existing definitions are diverse. Its characteristics constantly change during an active hemorrhage and, thus is difficult to define appropriately. METHODS: In this narrative, non-systematic review, we performed a literature search to retrieve data that could contribute to answering clinical questions on the definition and grading of severe hemorrhage and massive transfusion, identifying factors that predict and affect bleeding and transfusion-related mortality and describing the risks of re-exploration and the economic impact of severe bleeding in cardiac surgery. Results: Massive perioperative bleeding is currently described by indices of its rate and extent and the magnitude of the consequent blood products transfusion. It has a significant impact on mortality, service logistics, and hospital financing. Proper and early identification of a massive bleeding is possible. Among other factors, patient's co-morbidities, bleeding severity and transfusion volume seem to predict the associated mortality. Consequent to severe bleeding, re-exploration, is also a potentially hazardous adverse event that also affects morbidity and mortality. CONCLUSIONS: Severe perioperative hemorrhage in cardiac surgery carries significant morbidity and mortality. Currently, prediction and identification of massive bleeding is a feasible but incomplete clinical task despite the availability of effective treatment regimens. A still missing, compact definition of massive perioperative bleeding in cardiac surgery that incorporates all phases of treatment could augment clinical preparedness, allow for the development of accurate prediction tools and permit the application of well-validated protocols of management. Hippokratia 2016, 20(3): 179-186.
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AIM: The additive EuroSCORE system for predicting operative mortality of cardiac patients tends to underestimate the mortality risk of high risk patients and concomitantly to overestimate that of low risk patients. We propose a modification of stratification groups aiming at improving its precision. We also tested its ability to predict the length of postoperative mechanical ventilation of our patients. METHODS: The high risk group of the EuroSCORE system (>6 points) was divided into three additional groups (group I: 0-2 points, group II: 3-5 points, group III: 6-8 points, group IV: 9-13 points, group V: >14 points) thus producing a 5 classes system. In a group of 301 cardiac surgery patients operated on in a low volume cardiac center, we calculated the expected mortality rate for each EuroSCORE class, the calibration of the modified scoring system, the ROC and the corresponding AUC values and the relative risk of each predisposing factor used by the original EuroSCORE sytem. RESULTS: The proposed modification increased the discrimination ability of EuroSCORE in predicting mortality (Hosmer-Lemeshow P=0.78, ROC size: 0.791) and marginally affected its accuracy in predicting length of postoperative mechanical ventilation (Hosmer-Lemeshow: 0.11, ROC size: 0.711). Combined operations of CABG and valve replacement were shown to exert a statistically significant effect on mortality (odds ratio 3.85, CI: 1.15-12.87, P=0.028). CONCLUSION: The proposed modification of additive EuroSCORE can presumably increase its discrimination ability in predicting mortality of cardiac patients handled in a low volume cardiac center. The need for prolonged mechanical ventilation could be predicted with acceptable accuracy, possibly providing support in resource management.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Técnicas de Apoyo para la Decisión , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/terapia , Respiración Artificial , Anciano , Área Bajo la Curva , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Bases de Datos Factuales , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
PTP1B is a protein tyrosine phosphatase involved in insulin receptor desensitization. PTP1B inhibition prolongs the activated state of the receptor, practically enhancing the effect of insulin. Thus PTP1B has become a drug target for the treatment of type II diabetes. PTP1b is an enzyme with multiple binding sites for competitive and allosteric inhibitors. Prediction of inhibitory action using docking analysis has limited success in case of enzymes with multiple binding sites, since the selection of the right crystal structure depends on the kind of inhibitor. In the present study, a two-step strategy for the prediction of PTP1b inhibitory action was applied to 12 compounds. Based on the study of known inhibitors, we isolated the structural characteristics required for binding to each binding site. As a first step, 3D-structures of the molecules were produced and their structural parameters were measured and used for prediction of the binding site of the compound. These results were used for the selection of the appropriate crystal structure for docking analysis of each compound, and the final prediction was based on the estimated binding energies. This strategy effectively predicted the activity of all compounds. A linear correlation was found between estimated binding energy and inhibition measured in vitro (r = -0.894).
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Inhibidores Enzimáticos/química , Simulación del Acoplamiento Molecular , Proteína Tirosina Fosfatasa no Receptora Tipo 1/antagonistas & inhibidores , Sitios de Unión , Diseño de Fármacos , Humanos , Enlace de Hidrógeno , Modelos Moleculares , Unión Proteica , Conformación Proteica , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Relación Estructura-Actividad , TermodinámicaRESUMEN
Clinicians inevitably encounter patients who meet the diagnostic criteria for the metabolic syndrome (MetS); these criteria include central obesity, hypertension, atherogenic dyslipidaemia, and hyperglycaemia. Regardless of the variations in its definition, MetS may be associated with adverse outcomes in patients undergoing both cardiac and non-cardiac surgery. There is a paucity of data concerning the anaesthetic management of patients with MetS, and only a few observational (mainly retrospective) studies have investigated the association of MetS with perioperative outcomes. In this narrative review, we consider the impact of MetS on the occurrence of perioperative adverse events after cardiac and non-cardiac surgery. Metabolic syndrome has been associated with higher rates of cardiovascular, pulmonary, and renal perioperative events and wound infections compared with patients with a non-MetS profile. Metabolic syndrome has also been related to increased health service costs, prolonged hospital stay, and a greater need for posthospitalization care. Therefore, physicians should be able to recognize the MetS in the perioperative period in order to formulate management strategies that may modify any perianaesthetic and surgical risk. However, further research is needed in this field.
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Síndrome Metabólico/complicaciones , Complicaciones Posoperatorias/etiología , Anestesia/métodos , Fibrilación Atrial/etiología , Cirugía Bariátrica/efectos adversos , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Humanos , Morbilidad , Procedimientos Ortopédicos/efectos adversos , Periodo Perioperatorio , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
Materials often exhibit fundamentally new phenomena in reduced dimensions that potentially lead to novel applications. This is true for single-layer, two-dimensional semiconductor crystals of transition-metal dichalcogenides, MX2 (M = Mo, W and X = S, Se). They exhibit direct bandgaps with energies in the visible region at the two non-equivalent valleys in the Brillouin zone. This makes them suitable for optoelectronic applications that range from light-emitting diodes to light harvesting and light sensors, and to valleytronics. Here, we report the results of a magnetoluminescence study of WS2 single-layer crystals in which the strong spin-orbit interaction additionally locks the valley and spin degrees of freedom. The recombination of the negatively charged exciton in the presence of a two-dimensional electron gas (2DEG) is found to be circularly polarized at zero magnetic field despite being excited with unpolarized light, which indicates that the existence of a valley polarized 2DEG is caused by valley and spin locking and strong electron-electron interactions.
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BACKGROUND: Postoperative delirium and cognitive dysfunction are common in hospitalized patients. The aim of this study was to investigate whether postoperative ondansetron administration has a favorable effect on postoperative delirium and 30th day cognitive function and pain in patients undergoing surgery with general anaesthesia due to femoral or hip fracture. METHODS: A hundred and six patients aged >40 years old scheduled for a femoral or hip fracture rehabilitation surgery, were randomized on a double-blind protocol to receive postoperatively 4 ml of either ondansetron 8 mg (Group A) or placebo (Group B) daily i.v. for five days. Each patient was evaluated preoperatively and on the 2nd, 3rd, 4th and 5th day postoperatively with Confusion Assessment Method test, and preoperatively and on the 30th day postoperatively using a sensitive battery of neuropsychological, functional and pain tests. RESULTS: Patients of both groups did not differ preoperatively significantly in their basic characteristics and predisposing factors associated with postoperative delirium and cognitive dysfunction. The results showed that postoperative administration of ondansetron was followed by a lower incidence and duration of postoperative delirium and improved postoperative neurocognitive function on the 30th postoperative day, regardless of age or history of stroke. This was accompanied by a significant better postoperative functionality and less pain. CONCLUSION: The postoperative ondansetron administration seems to protect and might improve the cognitive function in patients undergoing surgery under general anesthesia. Ondansetron also seems to release analgesic effects.
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Trastornos del Conocimiento/prevención & control , Delirio/prevención & control , Ondansetrón/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Antagonistas de la Serotonina/uso terapéutico , Anciano , Anestesia General , Método Doble Ciego , Femenino , Fracturas del Fémur/cirugía , Fracturas de Cadera/cirugía , Humanos , Masculino , Dolor Postoperatorio/prevención & control , Factores de TiempoRESUMEN
BACKGROUND: Early treatment of breast cancer patients with loco-regional relapse or contralateral disease has been shown to improve survival. There is no current consensus on the optimal follow-up strategy. This study estimates the risk of isolated contralateral relapse (CR) after breast cancer surgery and its change over time, together with the efficacy of clinical examination, self-examination and mammography in the detection of CR. METHODS: Data from patients treated for early breast cancer at Guy's Hospital between 1990 and 1997 were collected and those with isolated contralateral recurrences were analysed. Life table analysis was performed and CR, CR-free and cumulative CR rates were calculated. Correlations were evaluated using Pearson's correlation coefficient. RESULTS: One thousand one hundred and forty-three women were included in the study and 23 patients had isolated CR. The median probability of CR was a constant 0.24% per year. Only one recurrence was found clinically at follow up, while the majority was detected through mammography and self-palpation. CONCLUSIONS: The risk of CR is low and constant with time. Contralateral mammography is useful and can detect the vast majority of contralateral recurrences. These findings may have practical implications especially on the planning of postmastectomy follow up.
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Neoplasias de la Mama/cirugía , Recurrencia Local de Neoplasia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/radioterapia , Autoexamen de Mamas , Detección Precoz del Cáncer/métodos , Femenino , Estudios de Seguimiento , Humanos , Tablas de Vida , Mamografía , Mastectomía Segmentaria/métodos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/diagnóstico , Cuidados PosoperatoriosRESUMEN
PURPOSE: To detect the incidence of CMV infection in spontaneous abortion in Thrace. METHODS: Genetic material from 143 fetuses aged from 11 to 39 weeks was examined. The material originated from various regions of Thrace. All fetuses and the respective placentas underwent routine histopathology. DNA was isolated from sections of paraffinized tissues. Detection of CMV in the DNA genomic samples was performed using a commercial PCR-based detection kit. RESULTS: From the 143 fetuses that were examined, two were found to be CMV positive. Pathological findings related to inflammatory corruptions were observed in the placentas of 97 embryos, including the CMV infected ones. CONCLUSIONS: This study indicates CMV-DNA infection in 1.4% of aborted fetuses. CMV infection incidence in aborted fetuses is similar to this reported in other European regions. The molecular technique of PCR applied on paraffin-embedded biopsy material is proven to be an accurate, valid and fast method for investigating the CMV infection in aborted fetuses.
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Aborto Espontáneo/virología , Infecciones por Citomegalovirus/complicaciones , Citomegalovirus/aislamiento & purificación , Complicaciones Infecciosas del Embarazo/virología , Feto Abortado/patología , Aborto Espontáneo/patología , Adolescente , Adulto , Femenino , Grecia , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Embarazo , Adulto JovenRESUMEN
PURPOSE: Bleeding during hepatectomy remains a major cause of mortality despite recent developments in surgical and anaesthetic techniques. To date there is no single surgical device that combines speed, efficient haemostasis and safety for the adjacent vital structures during parenchymal division. This article presents the Three Surgeon Technique (3ST), a novel method of parenchymal dissection for major hepatectomies and compare it with our standard radiofrequency ablation (RFA) - assisted technique. METHODS: 77 patients who underwent major liver resection were divided into two groups: 38 of them (group A) underwent 41 RFA-assisted liver resections and 39 (group B) underwent 41 hepatectomies with the 3ST. The data for the 3ST were prospectively collected and compared to the already collated RFA patient group. RESULTS: Blood transfusion was necessary in 28 and 13 patients in group A and B respectively (p=0.016), with an average of 1.7 and 0.6 units of red blood cells (p<0.001). The Pringle maneuver was not required with the 3ST. The mean time of parenchymal dissection was 90.49 and 77.52 min in group A and B, respectively (p=0.007). CONCLUSION: The 3ST is a novel, reliable and safe alternative to the stand alone RFA-assisted technique. It is a faster procedure, and requires less blood units transfusion.
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Pérdida de Sangre Quirúrgica/prevención & control , Transfusión Sanguínea/estadística & datos numéricos , Ablación por Catéter , Hepatectomía/mortalidad , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Anciano , Anciano de 80 o más Años , Disección , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Serous adenomas represent 1-2% of pancreatic neoplasms and typically are asymptomatic not requiring any treatment and simple observation is the option of choice. Although, they carry a realistic risk of malignancy despite the general view that they never become malignant. We report a case, which, according to our best knowledge is the 27th case reported in the literature. METHODS: We reviewed the literature by performing a search in Pub Med and Medline. RESULTS: A 86-year old patient known to have a serous cystadenoma of the pancreas treated conservatively through a close clinical and radiological follow up which was unattended for 4 years ending up to our emergency department suffering an acute abdomen. Exploratory laparotomy revealed a perforated prepyloric ulcer which was treated accordingly. Patient died some weeks later due to severe medical co morbidities. CONCLUSION: Serous cystic neoplasms of the pancreas carry a realistic risk of malignancy despite the general view that they never become malignant. In our opinion the treatment strategy of serous cystic neoplasms of the pancreas should be aggressive even in cases of remote metastases since prognosis of the disease is satisfactory.