RESUMEN
BACKGROUND: Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. METHODS: The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. DISCUSSION: With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.
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Neoplasias de la Próstata , Radiocirugia , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Estudios Prospectivos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/radioterapia , Hipofraccionamiento de la Dosis de Radiación , Radiocirugia/métodosRESUMEN
One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes. Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed. 50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkin's lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin's lymphoma: n=2).No clinically significant procedure-related complications were encountered. This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.
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Biopsia con Aguja/métodos , Broncoscopía/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Ganglios Linfáticos/patología , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Biopsia con Aguja/instrumentación , Broncoscopios , Femenino , Enfermedad de Hodgkin/patología , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Estudios Prospectivos , Sarcoidosis Pulmonar/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Instrumentos Quirúrgicos , Tuberculosis Pulmonar/patologíaRESUMEN
For patients who are known to have an impaired immune system, bone healing is often impaired. Therefore, it has been suggested that an effectively functioning immune system will have an influence on the quality of bone healing. Here, we demonstrate that cells within the fracture hematoma of immunologically restricted patients (1) exhibit a disturbed osteogenic differentiation (normal SPP1 but diminished RUNX2 expression), (2) show a strong inflammatory reaction (high IL8 and CXCR4), and (3) react on local hypoxia (high expression of HIF1A) but with inadequate target gene responses (diminished LDHA and PGK1 expression). Thus, it is already within the early inflammatory phase of fracture healing that the local gene expression in fracture hematomas of immunologically restricted patients points toward a critical regeneration.
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Regeneración Ósea/inmunología , Fracturas Óseas/inmunología , Hematoma/inmunología , Huésped Inmunocomprometido/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Hipoxia de la Célula/inmunología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/inmunología , Femenino , Fracturas Óseas/patología , Hematoma/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Interleucina-8/inmunología , Masculino , Persona de Mediana Edad , Osteogénesis/inmunología , Osteopontina/inmunología , Fosfoglicerato Quinasa/inmunología , Receptores CXCR4/inmunologíaRESUMEN
BACKGROUND: The proper positioning of patients before direct laryngoscopy is a key step that facilitates tracheal intubation. In obese patients, the 25 degree back-up or head-elevated laryngoscopic position, which is better than the supine position for tracheal intubation, is usually achieved by placing blankets or other devices under the patient's head and shoulders. This position can also be achieved by reconfiguring the normally flat operating room (OR) table by flexing the table at the trunk-thigh hinge and raising the back (trunk) portion of the table (OR table ramp). This table-ramp method can be used without the added expense of positioning devices, and it reduces the possibility of injury to the patient or providers that can occur during removal of such devices once tracheal intubation is achieved. In this study, we sought to determine if the table-ramp method of patient positioning was equivalent to the blanket method with regard to the time required for tracheal intubation. METHODS: Eighty-five adults with a Body Mass Index >30 kg/m(2), scheduled for elective surgery, consented to participate in this prospective randomized equivalence study conducted in a teaching hospital. The randomization scheme used permuted blocks with subjects equally allocated to be positioned using either the blanket method or the table-ramp method. The end-point in either case was to achieve a head-elevated position, where the patient's external auditory meatus and sternal notch were in the same horizontal plane. Although all patients were positioned by the same anesthesiologist, laryngoscopy and tracheal intubation were performed by trainees with various levels of expertise. Standard i.v. induction and tracheal intubation techniques were used. The time from loss of consciousness to the time after tracheal intubation when end-tidal CO(2) was detected was recorded. The effectiveness of mask ventilation and quality of laryngeal exposure were also noted. RESULTS: The mean time (SD) to tracheal intubation was 175 (66) s in the blanket group, as compared to 163 (71) s in the table-ramp group. Assuming the bounds for equivalence are -55,55 s, our study found a 95% confidence interval of -36.22, 13.52 s using two one-sided tests for equivalence corresponding to a significance level of 0.05. There was no difference in the number of attempts at laryngoscopy (P = 0.21) and tracheal intubation (P = 0.76) required to secure the airway between the two groups. CONCLUSIONS: Before induction of anesthesia, obese patients can be positioned with their head elevated above their shoulders on the operating table, on a ramp created by placing blankets under their upper body or by reconfiguring the OR table. For the purpose of direct laryngoscopy and tracheal intubation, these two methods are equivalent.
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Intubación Intratraqueal/métodos , Laringoscopía/métodos , Obesidad/cirugía , Postura , Adulto , Femenino , Cabeza , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
We describe a process by which we sought to determine how the addition of intraoperative neurophysiologic monitoring (IONM) impacted the management of cardiopulmonary bypass (CPB) during pediatric cardiac surgery. While maintaining a consistent team of surgeons, anesthesiologists, nurses, and perfusionists, a multi-modal, IONM program was established consisting of Near Infrared Spectroscopy, Transcranial Doppler, and eight channel electroencephalography. A retrospective review of cases from 1 year before the institution of the IONM program was compared with data obtained from cases performed after neurophysiologic monitoring was established as a standard of care for pediatric patients on CPB. This comparative analysis of CPB management revealed a significant increase in the use of donor blood added to the CPB circuit prime as well as in the maintenance of a higher hematocrit during the bypass period after the implementation of IONM. These changes in the management of pediatric CPB correlated with recommendations of previous studies that examined postoperative neurophysiologic outcomes, suggesting that these changes were not only consistent with best practices, but that the presence of IONM data facilitated a transition to evidence-based practice.
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Puente Cardiopulmonar/métodos , Electroencefalografía/métodos , Monitoreo Intraoperatorio/métodos , Espectroscopía Infrarroja Corta/métodos , Ultrasonografía Doppler Transcraneal/métodos , Hematócrito/métodos , Hemofiltración/métodos , Humanos , Lactante , Fenómenos Fisiológicos del Sistema Nervioso , Estudios RetrospectivosRESUMEN
BACKGROUND: Hyperglycemia during cardiac surgery in nondiabetic patients is a common finding associated with increased morbidity and mortality, but its predictors have not been studied to date. METHODS: To identify clinical and laboratory correlates of excessive and persistent blood glucose (BG) elevation during cardiopulmonary bypass (CPB) in nondiabetic patients, the authors reviewed 195 medical records. After exclusion of patients with preoperative BG >120 mg/dL and with missing preoperative BG data, 163 cases were included in the final analysis. Patients with BG > or =200 mg/dL during CPB and remaining > or =200 mg/dL either during or after CPB or at the first postoperative measurement formed the study group (n = 35). One case had insufficient data to determine group assignment and was not used in comparison. The remaining patients formed the control group (n = 127). RESULTS: BG was > or =200 mg/dL at least once perioperatively in 114 of 163 (70%) patients. It occurred during CPB in 100 of 163 (61%) cases and persisted beyond CPB in 35 of 162 (22%) cases. Univariate analysis revealed a significant difference between groups in preoperative use of angiotensin-converting enzyme (ACE) inhibitors (51% v 29%, p = 0.02), total dose of phenylephrine during CPB (14.1 mg +/- 10.6 mg v 10.3 +/- 9.6 mg, p = 0.003) and pre-CPB BG (123 +/- 22 mg/dL v 113 +/- 18 mg/dL, p = 0.02). In multivariate analysis, ACE inhibitors and pre-CPB BG remained statistically significant. CONCLUSIONS: Nondiabetic patients with excessive and persistent BG elevation during cardiac surgery are more likely to take ACE inhibitors preoperatively, show relatively high pre-CPB BG, and possibly require higher doses of vasoconstrictors during CPB.
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Puente Cardiopulmonar , Hiperglucemia/mortalidad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Glucemia/metabolismo , Cardiotónicos/uso terapéutico , Distribución de Chi-Cuadrado , Femenino , Humanos , Hiperglucemia/complicaciones , Masculino , Registros Médicos , Persona de Mediana Edad , Fenilefrina/uso terapéutico , Cuidados Preoperatorios , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The most common single-nucleotide polymorphism (SNP) of the human mu-opioid receptor (hMOR) gene occurs at position 118 (A118G) and results in substitution of asparagine to aspartate at the N-terminus. The purpose of the present study was to compare the pharmacological profile of several opioid agonists to heterologously expressed hMOR and N-type Ca(2+) channels in sympathetic neurons. cDNA constructs coding for wild-type and mutant hMOR were microinjected in rat superior cervical ganglion neurons and N-type Ca(2+) channel modulation was investigated using the whole cell variant of the patch-clamp technique. Concentration-response relationships were generated with the following selective MOR agonists: DAMGO, morphine, morphine-6-glucuronide (M-6-G), and endomorphin I. The estimated maximal inhibition for the agonists ranged from 52 to 64% for neurons expressing either hMOR subtype. The rank order of potencies for estimated EC(50) values (nM) in cells expressing wild-type hMOR was: DAMGO (31) >> morphine (76) congruent with M-6-G (77) congruent with endomorphin I (86). On the other hand, the rank order in mutant-expressing neurons was: DAMGO (14) >> morphine (39) >> endomorphin I (74) congruent with M-6-G (82), with a twofold leftward shift for both DAMGO and morphine. The DAMGO-mediated Ca(2+) current inhibition was abolished by the selective MOR blocker, CTAP, and by pertussis toxin pretreatment of neurons expressing either hMOR subtype. These results suggest that the A118G variant MOR exhibits an altered signal transduction pathway and may help explain the variability of responses to opiates observed with carriers of the mutant allele.
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Canales de Calcio Tipo N/genética , Canales de Calcio Tipo N/fisiología , Polimorfismo de Nucleótido Simple/genética , Polimorfismo de Nucleótido Simple/fisiología , Receptores Opioides mu/genética , Receptores Opioides mu/fisiología , Analgésicos Opioides/metabolismo , Analgésicos Opioides/farmacología , Animales , Separación Celular , ADN Complementario/genética , Relación Dosis-Respuesta a Droga , Electrofisiología , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Humanos , Masculino , Microinyecciones , Morfina/metabolismo , Morfina/farmacología , Derivados de la Morfina/farmacología , Mutación/fisiología , Neuronas/fisiología , Técnicas de Placa-Clamp , Toxina del Pertussis/farmacología , Ratas , Ratas Wistar , Ganglio Cervical Superior/citología , Ganglio Cervical Superior/fisiologíaRESUMEN
Chromosomal rearrangements involving the (sub)telomeres are an important cause of human genetic diseases: with the development of advanced molecular cytogenetic methods they have been identified as a major cause of mental retardation and/or congenital malformation syndromes. We identified a cryptic unbalanced de novo translocation 10p/13q by subtelomere FISH in a boy with mental and growth retardation (karyotype: 46,XY,der(10)t(10;13)(p15.1;q34)(D10S2488-,D13S296+)). Craniofacial dysmorphisms included frontal bossing, epicanthal folds, long philtrum, thin upper lip, short nose, mild retrognathy and a flat midface. In addition the patient had ASDII, a pyloric stenosis, bilateral inguinal hernias and cryptorchidism. His psychomotor development was significantly delayed. Microsatellite typing revealed the paternal origin of the two chromosomes involved in the rearrangement. By comparing our case with previously published patients with similar aberrations we conclude that the congenital malformations in our case are associated with the partial 10p deletion. The craniofacial features might be attributed to the 13q duplication. The identification of a 10p/13q translocation in our case highlights the importance of searching for cryptic subtelomeric imbalances in mentally retarded patients and helps to further delineate genotype-phenotype correlations in rare chromosomal disturbances.
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Anomalías Múltiples/genética , Cromosomas Humanos Par 10/genética , Cromosomas Humanos Par 13/genética , Translocación Genética , Preescolar , Aberraciones Cromosómicas , Anomalías Craneofaciales/genética , Femenino , Trastornos del Crecimiento/genética , Humanos , Hibridación Fluorescente in Situ/métodos , Discapacidad Intelectual/genética , Masculino , Repeticiones de Microsatélite , Padres , Fenotipo , Telómero/genéticaRESUMEN
BACKGROUND: Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization - induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers. METHODS: The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped. RESULTS: The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation. CONCLUSION: We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers.
RESUMEN
We investigated the efficacy of granisetron and dolasetron in preventing postoperative nausea and vomiting. Because the metabolism of the various antiemetic 5-hydroxytryptamine type 3 (5-HT3) antagonists involves different isoforms of the hepatic cytochrome P450 system, we examined the relationship between the clinical efficacy of these drugs and polymorphic cytochrome P450 2D6 (CYP2D6) genotype. This prospective, randomized, double-blind study involved 150 adult patients with a moderate to high risk for postoperative nausea and vomiting. All subjects received dexamethasone at induction of anesthesia followed by either 12.5 mg of dolasetron or 1 mg of granisetron. We analyzed the number of complete responders (no vomiting or rescue medication) during the first 24 hours after surgery. CYP2D6 genotyping was performed using a TaqMan real-time polymerase chain reaction. A complete response was more frequent in the granisetron group (54.7%) compared with the dolasetron group (38.7%, P < 0.05). In subjects receiving dolasetron, carriers of the duplication of the CYP2D6 allele predicting ultrarapid metabolizer status had more frequent vomiting episodes (P < 0.05) than patients in the granisetron group. It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.
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Citocromo P-450 CYP2D6/genética , Granisetrón/uso terapéutico , Indoles/uso terapéutico , Náusea y Vómito Posoperatorios/genética , Náusea y Vómito Posoperatorios/prevención & control , Quinolizinas/uso terapéutico , Adulto , Citocromo P-450 CYP2D6/metabolismo , Método Doble Ciego , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Náusea y Vómito Posoperatorios/enzimología , Estudios ProspectivosRESUMEN
BACKGROUND: Silver-Russell syndrome (SRS) is a heterogeneous malformation syndrome characterised by intrauterine and postnatal growth retardation (IUGR, PGR) and dysmorphisms. The basic causes are unknown, however in approximately 10% of patients a maternal uniparental disomy (UPD) of chromosome 7 or chromosomal aberrations can be detected. Four growth retarded children, two with SRS-like features, associated with maternal duplications of 11p15 have been described. Considering the involvement of this genomic region in Beckwith-Wiedemann overgrowth syndrome (BWS), we postulated that some cases of SRS--with an opposite phenotype to BWS--might also be caused by genomic disturbances in 11p15. METHODS: A total of 46 SRS patients were screened for genomic rearrangements in 11p15 by STR typing and FISH analysis. RESULTS: Two SRS patients with duplications of maternal 11p material in our study population (n = 46) were detected. In patient SR46, the duplicated region covered at least 9 Mb; FISH analysis revealed a translocation of 11p15 onto 10q. In patient SR90, additional 11p15 material (approximately 5 Mb) was translocated to the short arm of chromosome 15. CONCLUSIONS: We suggest that diagnostic testing for duplication in 11p15 should be offered to patients with severe IUGR and PGR with clinical signs reminiscent of SRS. SRS is a genetically heterogeneous condition and patients with a maternal duplication of 11p15.5 may form an important subgroup.
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Anomalías Múltiples/genética , Aberraciones Cromosómicas , Cromosomas Humanos Par 11/genética , Enanismo/genética , Retardo del Crecimiento Fetal/genética , Anomalías Múltiples/diagnóstico , Análisis Mutacional de ADN , Enanismo/diagnóstico , Femenino , Retardo del Crecimiento Fetal/diagnóstico , Duplicación de Gen , Pruebas Genéticas , Humanos , Cariotipificación , Masculino , Síndrome , Secuencias Repetidas en Tándem/genética , Translocación Genética , Disomía UniparentalAsunto(s)
Cromosomas Humanos X , Insuficiencia Ovárica Primaria/genética , Eliminación de Secuencia , Adulto , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Asesoramiento Genético , Humanos , Cariotipificación , Proteínas del Tejido Nervioso/genética , Linaje , Proteínas de Unión al ARN/genética , Repeticiones de TrinucleótidosRESUMEN
Proton magnetic resonance spectroscopic data ((1)H-MR spectroscopy) of patients with 18q deletion syndrome have not yet been reported. (1)H-MR spectroscopy, performed in an affected 2-year-old girl with markedly delayed neuromotor development and typical supratentorial white-matter disease (WMD), showed an increase of choline and alpha-glutamate concentrations. Eight months later, simultaneously with clinical improvement, alpha-glutamate had normalised whereas choline remained slightly increased. Active demyelination or increased myelin turnover might contribute to the hitherto unexplained WMD of this rare disorder.
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Ácido Aspártico/análogos & derivados , Encefalopatías/metabolismo , Deleción Cromosómica , Cromosomas Humanos Par 18/genética , Enfermedades Desmielinizantes/diagnóstico , Espectroscopía de Resonancia Magnética , Vaina de Mielina/metabolismo , Ácido Aspártico/análisis , Colina/análisis , Femenino , Estudios de Seguimiento , Ácido Glutámico/análisis , Humanos , Lactante , Inositol/análisis , Imagen por Resonancia MagnéticaRESUMEN
UNLABELLED: The dose-response curve for the effect of volatile anesthetics on the somatosensory evoked potential (SEP) is well described, but for propofol, the large dose segment of the curve is undefined. We describe the effect of increasing plasma concentrations of propofol on cortical SEPs in 18 rats. After surgical preparation under ketamine anesthesia, a remifentanil infusion was begun at 2.5, 5, or 10 microg x kg(-1) x min(-1). After 20 min, the propofol infusion was initiated at 20 mg x kg(-1) x h(-1) and was increased to 40, 60, and 80 mg x kg(-1) x h(-1) at 20-min intervals. SEP was recorded before remifentanil infusion, before propofol infusion rate changes, and 30 min after discontinuing propofol infusion. In six additional rats, the plasma concentrations of propofol after each 20-min infusion were measured using gas chromatography. Remifentanil did not have a significant effect, but propofol significantly depressed the SEP amplitude and prolonged the latency at infusion rates of 40 mg x kg(-1) x h(-1) and more. Propofol's effect was dose-dependent, but even at 80 mg x kg(-1) x h(-1) with an estimated plasma concentration of 31.6 +/- 3.4 microg/mL (10.8 50% effective concentration), a measurable response was present in 44.5% of rats. These results suggest that even at large doses, propofol and remifentanil provide adequate conditions for SEP monitoring. IMPLICATIONS: Rats demonstrate dose-dependent somatosensory evoked potential (SEP) suppression with propofol but not with remifentanil. However, SEP suppression by 50% occurred only at large (1.5 EC(50)) concentrations of propofol, and a measurable SEP was present in 8 of 18 rats, even at 10.8 EC(50).
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Anestésicos Intravenosos/farmacología , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Propofol/farmacología , Analgésicos Opioides/farmacología , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/sangre , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Inyecciones Intravenosas , Masculino , Piperidinas/administración & dosificación , Piperidinas/farmacología , Propofol/administración & dosificación , Propofol/sangre , Ratas , Ratas Sprague-Dawley , RemifentaniloRESUMEN
BACKGROUND: Mu opioid agonists suppress natural killer (NK) cell activity in animal models. Studies in human volunteers, however, have yielded conflicting results, with morphine suppressing and fentanyl increasing NK cell activity. This study evaluated the effect of a constant 8-h infusion of remifentanil on NK cell number and function in human volunteers. METHODS: After IRB approval and informed consent was obtained, 10 healthy volunteers underwent an 11 pm to 7 am infusion of saline, and at least 1 week later an infusion of 0.02-0.04 microg x kg(-1) min(-1) remifentanil. Blood was collected at 7 am for measurement of NK cell cytotoxicity using a (51)Cr release assay and measurement of NK cell number using fluorescent flow cytometry. RESULTS: Median and range of the total NK cell cytotoxicity (KU ml(-1)) was 745.0 (498.3-1483.6) on the control morning and 818.6 (238.5-1454.5) on the morning following the remifentanil infusion. Neither the number of NK cells ml(-1) (2.5 x 10(5) (1.4 x 10(5)-4.2 x 10(5)) vs 2.7 x 10(5) (1.1 x 10(5)-4.4 x 10(5))) nor the cytotoxicity per 1000 NK cells (KU 1000 NK cells(-1)) (3.0 (1.8-5.2) vs 2.9 (0.9-6.7)) changed between the control and remifentanil conditions. CONCLUSIONS: An 8-h infusion of remifentanil did not affect NK cell activity in normal volunteers. This result differs from previous findings of morphine-induced NK cell activity suppression and fentanyl-induced NK cell activity enhancement in normal volunteers.
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Analgésicos Opioides/farmacología , Citotoxicidad Inmunológica/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Piperidinas/farmacología , Adulto , Femenino , Humanos , Infusiones Intravenosas , Células Asesinas Naturales/inmunología , Recuento de Linfocitos , Masculino , Remifentanilo , Respiración/efectos de los fármacos , Método Simple CiegoRESUMEN
OBJECTIVE: We sought to estimate the prevalence and severity of tinnitus in patients with chronic pain. STUDY DESIGN AND SETTING: We conducted a prospective nonrandomized study in which a survey and the Tinnitus Handicap Inventory (THI) were distributed at a tertiary chronic pain clinic. RESULTS: Seventy-two patients participated. 50 women (mean age, 53 years) and 22 men (mean age, 47.5 years); 54.2% reported having tinnitus. There was an even distribution of patients reporting the onset of tinnitus as before versus after the onset of pain. Four patients reported a direct association between tinnitus and pain. The mean THI score was 27 (of 100) (n = 35). Fifteen subjects scored less than 16, indicating no handicap, and 4 scored over 58, indicating a severe handicap. CONCLUSION: The study results suggest a high incidence of tinnitus within this population. There were few strong associations between pain and tinnitus. Tinnitus does not significantly handicap the majority of these patients. SIGNIFICANCE: Tinnitus is a common symptom in the chronic pain population but is not a significant problem for these patients.
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Dolor/epidemiología , Acúfeno/epidemiología , Adolescente , Anciano , Enfermedad Crónica , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Dolor/complicaciones , Prevalencia , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Acúfeno/complicacionesRESUMEN
UNLABELLED: Successful somatosensory-evoked potential (SEP) monitoring has been performed during the administration of dexmedetomidine to patients, but a systematic investigation of the dose response of the SEP to dexmedetomidine has not been reported. In this study, we evaluated the effect of a range of dexmedetomidine doses on the cortical SEP in rats. Twelve rats were initially anesthetized with ketamine and the lungs were mechanically ventilated. Femoral arterial and venous catheters were placed. Anesthesia was maintained with constant infusions of remifentanil (5-15 microg. kg(-1). min(-1)) and vecuronium (56 microg. kg(-1). min(-1)). Dexmedetomidine was infused at 0.1, 0.25, 0.5, 1.0, and 2.0 microg. kg(-1). min(-1) in a stepwise manner with 10-min infusion periods at each step. In eight rats, an additional large-dose infusion of dexmedetomidine at 10 microg. kg(-1). min(-1) was administered for 30 min. The cortical SEPs were recorded after stimulation of the tibial nerve. At all infusion rates, there was a statistically insignificant increase in the SEP amplitude. Dexmedetomidine consistently increased the SEP latency, but these increases were not statistically significant. These data demonstrate that dexmedetomidine maintains technically adequate conditions for SEP monitoring in rats and provides support for future studies of the effect of dexmedetomidine on SEP monitoring in humans. IMPLICATIONS: In rats, the administration of a wide range of infusion rates of dexmedetomidine did not significantly affect the somatosensory-evoked potential. These results suggest that dexmedetomidine might be a useful adjunctive drug in patients undergoing intraoperative somatosensory-evoked potential monitoring.
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Dexmedetomidina/farmacología , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Hipnóticos y Sedantes/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Dexmedetomidina/administración & dosificación , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/administración & dosificación , Infusiones Intravenosas , Masculino , Ratas , Ratas Sprague-Dawley , Nervio Tibial/efectos de los fármacos , Nervio Tibial/fisiologíaRESUMEN
The eukaryotic microfilament system is regulated in part through the nucleotide- and cation-dependent conformation of the actin molecule. In this review, recent literature on the crystal and solution structures of actin and other actin-superfamily proteins is summarized. Furthermore, the structure of the nucleotide binding cleft is discussed in terms of the mechanism of ATP hydrolysis and P(i) release. Two distinct domain movements are suggested to participate in the regulation of actin. (1) High-affinity binding of Mg(2+) to actin induces a rearrangement of side chains in the nucleotide binding site leading to an increased ATPase activity and polymerizability, as well as a rotation of subdomain 2 which is mediated by the hydroxyl of serine-14. (2) Hydrolysis of ATP and subsequent release of inorganic phosphate lead to a butterfly-like opening of the actin molecule brought about by a shearing in the interdomain helix 135-150. These domain rearrangements modulate the interaction of actin with a variety of different proteins, and conversely, protein binding to actin can restrict these conformational changes, with ultimate effects on the assembly state of the microfilament system.
Asunto(s)
Actinas/química , Adenosina Trifosfatasas/química , Conformación Proteica , Adenosina Trifosfato/química , Sitios de Unión , Catálisis , Cristalización , Modelos Moleculares , Miosinas/química , Fosfatos/química , Estructura Terciaria de Proteína , SolucionesRESUMEN
Polymerization and depolymerization of cytoskeletal elements maintaining cytoplasmic stiffness are key factors in the control of cell crawling. Rheometry is a significant tool in determining the mechanical properties of the single elements in vitro. Viscoelasticity of gels formed by these polymers strongly depends on both the length and the associations of the filaments (e.g. entanglements, annealings and side-by-side associations). Ultrasound attenuation is related to viscosity, sound velocity and supramolecular structures in the sample. In combination with a small glass fibre (2 mm x 50 microm), serving as a viscosity sensor, an acoustic microscope was used to measure the elasticity and acoustic attenuation of actin solutions. Changes in acoustic attenuation of polymerizing actin by far exceed the values expected from calculations based on changes in viscosity and sound velocity. During the lag-phase of actin polymerization, attenuation slightly decreases, depending on actin concentration. After the half-maximum viscosity is accomplished and elasticity turns into steady state, attenuation distinctly rises. Changes in ultrasound attenuation depend on actin concentration, and they are modulated by the addition of alpha-actinin, cytochalasin D and profilin. Thus absorption and scattering of sound on the polymerization of actin is related to the packing density of the actin net, entanglements and the length of the actin filaments. Shortening of actin filaments by cytochalasin D was also confirmed by electron micrographs and falling-ball viscosimetry. In addition to viscosity and elasticity, the attenuation of sound proved to be a valuable parameter in characterizing actin polymerization and the supramolecular associations of F-actin.