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1.
Exerc Immunol Rev ; 24: 26-34, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29461966

RESUMEN

There are common pathways by which psychological stress and exercise stress alter immunity. However, it remains unknown whether psychological stress plays a role in the in vivo immune response to exercise. We examined the relationship between anxiety and perceived psychological stress reported before exercise and in vivo immunity after exercise using skin sensitisation with Diphenylcyclopropenone (DPCP). In a randomised design, sixty four, thoroughly familiarised, males completed widely used psychological instruments to assess state-anxiety and perceived psychological stress before exercise, and ran either 30 minutes at 60% (30MI) or 80% (30HI) V . O2peak, 120 minutes at 60% (120MI) V . O2peak or rested (CON) before DPCP sensitisation. Cutaneous recall to DPCP was measured as the dermal thickening response to a low-dose series DPCP challenge 4-weeks after sensitisation. After accounting for exercise (R2 = 0.20; P < 0.01), multiple-regression showed that pre-exercise state-anxiety (STAI-S; ΔR2 = 0.19; P < 0.01) and perceived psychological stress (ΔR2 = 0.13; P < 0.05) were moderately associated with the DPCP response after exercise. The STAI-S scores before exercise were considered low-to-moderate in these familiarised individuals (median split; mean STAI-S of low 25 and moderate 34). Further examination showed that the DPCP response after exercise (30MI, 30HI or 120MI) was 62% lower in those reporting low vs. moderate state-anxiety before exercise (mean difference in dermal thickening: -2.6 mm; 95% CI: -0.8 to -4.4 mm; P < 0.01). As such, the results indicate a beneficial effect of moderate (vs. low) state-anxiety and perceived psychological stress on in vivo immunity after exercise. Moreover, correlations were of comparable strength for the relationship between physiological stress (heart rate training impulse) and the summed dermal response to DPCP (r = -0.37; 95% CI: -0.05 to -0.62; P = 0.01), and state-anxiety and the summed dermal response to DPCP (r = 0.39; 95% CI: 0.08 to 0.63; P < 0.01). In conclusion, state-anxiety and perceived psychological stress levels before exercise play animportant role in determining the strength of the in vivo immune response after exercise. These findings indicate a similar strength relationship for the level of state-anxiety prior to exercise and the level of physiological stress during exercise with the in vivo immune response after exercise. Future research is required to investigate exercise-immune responses in athletes, military personnel and others in physically demanding occupations experiencing higher levels of psychological stress than those reported in this study e.g. related to important competition, military operations and major life events. Nevertheless, the present findings support the recommendation that exercise scientists should account for anxiety and psychological stress when examining the immune response to exercise.


Asunto(s)
Ansiedad/inmunología , Dermatitis por Contacto/inmunología , Ejercicio Físico/fisiología , Estrés Psicológico/inmunología , Adulto , Ciclopropanos/administración & dosificación , Epinefrina/sangre , Humanos , Hidrocortisona/sangre , Masculino , Consumo de Oxígeno , Piel/efectos de los fármacos , Grosor de los Pliegues Cutáneos , Estrés Fisiológico , Adulto Joven
2.
Am J Respir Crit Care Med ; 194(6): 692-700, 2016 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-26967568

RESUMEN

RATIONALE: It is unclear how septic shock causes acute kidney injury (AKI) and whether this is associated with histological change. OBJECTIVES: We aimed to determine the nature and extent of changes in renal structure and function over time in an ovine model of septic shock. METHODS: Fifteen sheep were instrumented with a renal artery flow probe and renal vein cannula. Ten were given intravenous Escherichia coli to induce septic shock, and five acted as controls. Animals were mechanically ventilated for 48 hours, while receiving protocol-guided parenteral fluids and a norepinephrine infusion to maintain mean arterial pressure. Renal biopsies were taken every 24 hours or whenever animals were oliguric for 2 hours. A renal pathologist, blinded to tissue source, systematically quantified histological appearance by light and electron microscopy for 31 prespecified structural changes. MEASUREMENTS AND MAIN RESULTS: Sheep given E. coli developed septic shock, oliguria, increased serum creatinine, and reduced creatinine clearance (AKI), but there were no changes over time in renal blood flow between groups (P > 0.30) or over time within groups (P > 0.50). Renal oxygen consumption increased only in nonseptic animals (P = 0.01), but there was no between-group difference in renal lactate flux (P > 0.50). There was little structural disturbance in all biopsies and, although some cellular appearances changed over time, the only difference between septic and nonseptic animals was mesangial expansion on electron microscopy. CONCLUSIONS: In an intensive care-supported model of gram-negative septic shock, early AKI was not associated with changes in renal blood flow, oxygen delivery, or histological appearance. Other mechanisms must contribute to septic AKI.


Asunto(s)
Riñón/fisiopatología , Choque Séptico/fisiopatología , Lesión Renal Aguda/etiología , Animales , Biopsia , Presión Sanguínea , Gasto Cardíaco , Modelos Animales de Enfermedad , Femenino , Riñón/patología , Circulación Renal , Ovinos , Choque Séptico/complicaciones , Choque Séptico/patología
3.
Gynecol Oncol ; 133(2): 268-73, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24556059

RESUMEN

OBJECTIVE: Permanent interstitial brachytherapy is an ideal yet underutilized treatment modality for accessible, small volume gynecological malignancies. We present early clinical results utilizing a new permanent isotope, Cs-131. METHODS: A retrospective review was performed evaluating patients treated with Cs-131 permanent interstitial radiation at our institution from July 2011 through June 2013. Doses were most commonly prescribed and calculated to a depth of 5mm using Paterson-Parker planar implant rules for Au-198. This activity was converted to air-kerma strength (U). A conversion factor of 1.1 was applied based on RBE calculations, clinical observation and experience. RESULTS: 14 patients were identified among whom 17 Cs-131 implants were performed. Seven patients were implanted as sole therapy, and a median dose of 50 Gy was delivered. Ten implants were performed as boost within a more extensive radiation treatment plan. In these patients, a median implant dose of 27.5 Gy was used and the median total dose delivered in combination was 78.25 Gy. After a median follow up of 12 months, the actuarial local control rate was 84.4%. A very low level of grade 1-3 reactions was observed with no fistula formations or other severe side effects. CONCLUSIONS: Permanent interstitial brachytherapy with Cs-131 was well tolerated with favorable early results compared to other series. Cs-131 has multiple favorable properties, including minimal radiation exposure to treating staff, and should be considered as a therapeutic option in appropriately selected patients. A methodology for dose prescription, calculation of radioactivity required and distribution of the isotope is also presented.


Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Carcinoma Papilar/radioterapia , Carcinoma de Células Escamosas/radioterapia , Radioisótopos de Cesio/uso terapéutico , Neoplasias de los Genitales Femeninos/radioterapia , Melanoma/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma de Células Claras/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Endometriales/radioterapia , Neoplasias de las Trompas Uterinas/radioterapia , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias Vaginales/radioterapia
4.
Sleep ; 46(1)2023 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-36112383

RESUMEN

STUDY OBJECTIVES: Prospectively examine the association between sleep restriction, perceived sleep quality (PSQ) and upper respiratory tract infection (URTI). METHODS: In 1318 military recruits (68% males) self-reported sleep was assessed at the beginning and end of a 12-week training course. Sleep restriction was defined as an individualized reduction in sleep duration of ≥2 hours/night compared with civilian life. URTIs were retrieved from medical records. RESULTS: On commencing training, approximately half of recruits were sleep restricted (52%; 2.1 ± 1.6 h); despite the sleep debt, 58% of recruits with sleep restriction reported good PSQ. Regression adjusted for covariates showed that recruits commencing training with sleep restriction were more likely to suffer URTI during the course (OR = 2.93, 95% CI 1.29-6.69, p = .011). Moderation analysis showed this finding was driven by poor PSQ (B = -1.12, SE 0.50, p = .023), as no significant association between sleep restriction and URTI was observed in recruits reporting good PSQ, despite a similar magnitude of sleep restriction during training. Associations remained in the population completing training, accounting for loss to follow-up. Recruits reporting poor PSQ when healthy at the start and end of training were more susceptible to URTI (OR = 3.16, 95% CI 1.31-7.61, p = .010, vs good PSQ). CONCLUSION: Good perceived sleep quality was associated with protection against the raised risk of respiratory infection during sleep restriction. Studies should determine whether improvements in sleep quality arising from behavioral sleep interventions translate to reduced respiratory infection during sleep restriction.


Asunto(s)
Infecciones del Sistema Respiratorio , Calidad del Sueño , Masculino , Humanos , Adulto Joven , Femenino , Sueño , Privación de Sueño/complicaciones , Autoinforme , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/prevención & control
5.
Transfusion ; 52(11): 2445-51, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22413968

RESUMEN

BACKGROUND: Blood transfusion management strategies minimize transfusion-associated risks, enhance outcomes, and reduce costs. We explored an association of discharge hemoglobin (Hb) with pretransfusion Hb, transfusion indications, and red blood cell (RBC) transfusions. We stipulate that patients with discharge Hb concentrations greater than 10.0 g/dL, or even 9.0 g/dL, received excessive RBC transfusions. STUDY DESIGN AND METHODS: We examined aggregate data from five hospitals and for one of the hospitals, the focus hospital, we reviewed patient records for a period of 6 months. Data analyses included number of RBC units transfused and Hb values before transfusion, after transfusion, and at discharge. RESULTS: In aggregate, 27% to 47% patients had discharge Hb levels greater than 10.0 g/dL. At the focus hospital, 27% had a discharge Hb level greater than 10 g/dL and 50.3% had a discharge Hb level greater than 9.0 g/dL. At the focus hospital, the mean Hb trigger for transfusion was a Hb level of 7.3 g/dL; the mean posttransfusion Hb level was 9.3 g/dL and mean discharge Hb level was 9.2 g/dL. Overall, 76% of the transfusions were of an even number of RBC units. CONCLUSION: In aggregate, overutilization exceeded 20%. At the focus hospital, approximately one-quarter of patients receiving transfusions had a Hb concentration greater than 10.0 g/dL at discharge. Transfused patients' discharge Hb concentration represents an effective indicator for retrospective monitoring of transfusion appropriateness. In light of the large number of patients receiving even number transfusions, reviewing Hb levels after transfusion of each RBC unit could reduce unnecessary transfusions. Retrospective review of discharge Hb data focuses providers on transfusion outcomes and affords an educational opportunity for blood utilization management.


Asunto(s)
Transfusión de Eritrocitos/estadística & datos numéricos , Transfusión de Eritrocitos/normas , Hemoglobinas/metabolismo , Hemorragia/terapia , Alta del Paciente/normas , Adulto , Bancos de Sangre/economía , Bancos de Sangre/normas , Bancos de Sangre/estadística & datos numéricos , Transfusión de Eritrocitos/economía , Femenino , Hemorragia/epidemiología , Hospitales de Enseñanza/economía , Hospitales de Enseñanza/normas , Humanos , Kansas/epidemiología , Masculino , Persona de Mediana Edad , Alta del Paciente/economía , Embarazo , Estudios Retrospectivos , Gestión de Riesgos/economía , Gestión de Riesgos/normas , Centros de Atención Terciaria/economía , Centros de Atención Terciaria/normas , Centros Traumatológicos/economía , Centros Traumatológicos/normas
6.
J Anesth ; 2012 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-22290734

RESUMEN

PURPOSE: Our aim was to determine the incidence of difficult intubation during pregnancy-related surgery at a high-risk, high-volume teaching institution. METHODS: Airway experience was analyzed among patients who had pregnancy-related surgery under general anesthesia from January 2001 through February 2006. A difficult airway was defined as needing three or more direct laryngoscopy (DL) attempts, use of the additional airway equipment after the DL attempts, or conversion to regional anesthesia due to inability to intubate. Airway characteristics were compared between patients with and without a difficult airway. In addition, pre- and postoperative airway evaluations were compared to identify factors closely related to changes from pregnancy. RESULTS: In a total of 30,766 operations, 2,158 (7%) were performed with general anesthesia. Among these, 1,026 (47.5%) were for emergency cesarean delivery (CD), 610 (28.3%) for nonemergency CD, and 522 (24.2%) for non-CD procedures. A total of 12 patients (0.56%) were identified as having a difficult airway. Four patients were intubated with further DL attempts; others required mask ventilation and other airway equipment. Two patients were ventilated through a laryngeal mask airway without further intubation attempts. Ten of the 12 difficult airway cases were encountered by residents during their first year of clinical anesthesia training. There were no maternal or fetal complications except one possible aspiration. CONCLUSION: Unanticipated difficult airways accounted for 0.56% of all pregnancy-related surgical patients. More than 99.9% of all obstetric patients could be intubated. A difficult airway is more likely to be encountered by anesthesia providers with <1 year of experience. Proper use of airway equipment may help secure the obstetric airway or provide adequate ventilation. Emergency CD did not add an additional level of difficulty over nonemergency CD.

7.
J Clin Anesth ; 75: 110470, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34364099

RESUMEN

STUDY OBJECTIVE: In the initial description of the serratus anterior plane block (SAPB), both superficial and deep SAPB provided effective blockade. The purpose of this study was to investigate the difference in opioid consumption and postoperative analgesia between superficial and deep SAPB for patients undergoing mastectomy. DESIGN: Randomized prospective trial. SETTING: Academic hospital. PATIENTS: 64 women, >18 years of age, ASA I-III, undergoing single or bilateral mastectomy, with and without lymph node biopsy, with and without tissue expander reconstruction. INTERVENTION: Either superficial or deep SAPB by an ultrasound-guided technique in addition to multimodal analgesia. MEASUREMENTS: The primary outcome was opioid consumption in the first 24 h. Secondary outcomes were pain scores, satisfaction scores, incidence of PONV, length of stay and block performance time. RESULTS: Subjects who received a deep SAPB required 30% less oral morphine equivalents (OME) (113.5 mg vs. 147 mg, p = 0.009) and reported lower pain scores. There were no significant differences in satisfaction scores, incidence of PONV, LOS, or block performance time between the two groups. CONCLUSION: There was a significant difference in opioid consumption between the deep and superficial SAPB groups. Subjects in the deep SAPB group had lower pain scores at 12 h; however, the difference was not statistically significant at other time points. While both the superficial and the deep SAPB can be used for post-operative analgesia in patients undergoing mastectomy, our study suggests that the deep SAPB may improve analgesia to a greater degree than the superficial SAPB as shown through decreased opioid consumption of 30% over a 24-h period post-block. CLINICAL TRIAL NUMBER AND REGISTRY URL: clinicaltrials.gov: NCT03154658.


Asunto(s)
Analgesia , Neoplasias de la Mama , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía/efectos adversos , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Estudios Prospectivos
8.
Med Sci Sports Exerc ; 53(7): 1505-1516, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-33481482

RESUMEN

PURPOSE: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training.


Asunto(s)
Colecalciferol/administración & dosificación , Personal Militar , Infecciones del Sistema Respiratorio/prevención & control , Infecciones del Sistema Respiratorio/terapia , Luz Solar , Administración Oral , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Inmunidad Mucosa , Masculino , Encuestas y Cuestionarios , Adulto Joven
9.
J Pharmacol Exp Ther ; 335(3): 781-7, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20855445

RESUMEN

Adenosine clearly regulates coronary blood flow (CBF); however, contributions of specific adenosine receptor (AR) subtypes (A(1), A(2A), A(2B), A(3)) to CBF in swine have not been determined. ARs generally decrease (A(1), A(3)) or increase (A(2A), A(2B)) cyclic adenosine monophosphate, a major mediator of vasodilation. We hypothesized that A(1) antagonism potentiates coronary vasodilation and coronary stent deployment in dyslipidemic Ossabaw swine elicits impaired vasodilation to adenosine that is associated with increased A(1)/A(2A) expression. The left main coronary artery was accessed with a guiding catheter allowing intracoronary infusions. After placement of a flow wire into the left circumflex coronary artery the responses to bolus infusions of adenosine were obtained. Steady-state infusion of AR-specific agents was achieved by using a small catheter fed over the flow wire in control pigs. CBF was increased by the A(2)-nonselective agonist 2-phenylaminoadenosine (CV1808) in a dose-dependent manner. Baseline CBF was increased by the highly A(1)-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), but not changed by other AR-specific agents. The nonselective A(2) antagonist 3,7-dimethyl-1-propargylxanthine and A(2A)-selective antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385) abolished adenosine-induced CBF, whereas A(2B) and A(3) antagonism had no effect. Dyslipidemia and stenting decreased adenosine-induced CBF ∼70%, whereas A(1), A(2A), and A(2B) mRNA were up-regulated in dyslipidemic versus control >5-fold and there was no change in the ratio of A(1)/A(2A) protein in microvessels distal to the stent. In control Ossabaw swine A(1) antagonism by DPCPX positively regulated basal CBF. Impaired adenosine-induced CBF after stenting in dyslipidemia is most likely caused by the altered balance between A(1) and A(2A) signaling, not receptor expression.


Asunto(s)
Circulación Coronaria/fisiología , Receptores Purinérgicos P1/fisiología , Porcinos Enanos/fisiología , Adenosina/farmacología , Agonistas del Receptor de Adenosina A2/administración & dosificación , Agonistas del Receptor de Adenosina A2/farmacología , Antagonistas del Receptor de Adenosina A2/administración & dosificación , Antagonistas del Receptor de Adenosina A2/farmacología , Animales , Colesterol/sangre , Circulación Coronaria/efectos de los fármacos , Grasas de la Dieta/farmacología , Expresión Génica/genética , Hemodinámica/fisiología , Hiperlipidemias/sangre , Hiperlipidemias/inducido químicamente , Hiperlipidemias/metabolismo , Hiperlipidemias/fisiopatología , Lipoproteínas/sangre , Masculino , Microvasos/metabolismo , Receptor de Adenosina A1/fisiología , Receptor de Adenosina A2A/fisiología , Receptor de Adenosina A2B/fisiología , Receptor de Adenosina A3/fisiología , Stents/efectos adversos , Porcinos , Triglicéridos/sangre , Regulación hacia Arriba/genética
10.
Saf Sci ; 120: 402-410, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31787806

RESUMEN

National culture colors nearly every aspect of human behavior (Javidan et al., 2006). Despite this truism, the concept has yet to be integrated into organizational safety culture theory. The purpose of this article is to bring awareness as to how national culture can influence organizational safety culture. We do so by theorizing that the shared organizational beliefs, assumptions, and values related to safety (i.e., the anthropologic component of safety culture) are a reflection of the national culture in which the organization's workers are embedded. These organizational values, beliefs, and assumptions directly influence worker perceptions of organizational life and their behavioral choices. Given this prospectively strong direct influence on organizational behavior, we reason that the effectiveness of different organizational structure designs, safety management practices, and leadership characteristics (i.e., safety culture's normative component) can depend on characteristics of the national culture within which the organization resides. We conclude by providing a few key practical suggestions and directions for future research.

11.
Front Immunol ; 10: 1178, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31231369

RESUMEN

Tears have attracted interest as a minimally-invasive biological fluid from which to assess biomarkers. Lactoferrin (Lf) and lysozyme (Lys) are abundant in the tear fluid and have antimicrobial properties. Since the eye is a portal for infection transmission, assessment of immune status at the ocular surface may be clinically relevant. Therefore, the aim of this series of studies was to investigate the tear fluid antimicrobial proteins (AMPs) Lf and Lys as biomarkers of mucosal immune status. To be considered biomarkers of interest, we would expect tear AMPs to respond to stressors known to perturb immunity but be robust to confounding variables, and to be lower in participants with heightened risk or incidence of illness. We investigated the relationship between tear AMPs and upper respiratory tract infection (URTI; study 1) as well as the response of tear AMPs to prolonged treadmill exercise (study 2) and dehydration (study 3). Study 1 was a prospective cohort study conducted during the common cold season whereas studies 2 and 3 used repeated-measures crossover designs. In study 1, tear Lys concentration (C) as well as tear AMP secretion rates (SRs) were lower in individuals who reported pathogen-confirmed URTI (n = 9) throughout the observation period than in healthy, pathogen-free controls (n = 17; Lys-C, P = 0.002, d = 0.85; Lys-SR, P < 0.001, d = 1.00; Lf-SR, P = 0.018, d = 0.66). Tear AMP secretion rates were also lower in contact lens wearers. In study 2, tear AMP SRs were 42-49% lower at 30 min-1 h post-exercise vs. pre-exercise (P < 0.001, d = 0.80-0.93). Finally, in study 3, tear AMPs were not influenced by dehydration, although tear AMP concentrations (but not secretion rates) displayed diurnal variation. We conclude that Lf and Lys have potential as biomarkers of mucosal immune competence; in particular, whether these markers are lower in infection-prone individuals warrants further investigation.


Asunto(s)
Biomarcadores/metabolismo , Deshidratación/metabolismo , Ejercicio Físico/fisiología , Lactoferrina/metabolismo , Muramidasa/metabolismo , Infecciones del Sistema Respiratorio/metabolismo , Lágrimas/metabolismo , Adolescente , Adulto , Femenino , Humanos , Inmunidad Mucosa , Inmunocompetencia , Masculino , Adulto Joven
13.
Coron Artery Dis ; 19(4): 217-26, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18480664

RESUMEN

Leukemia inhibitory factor (LIF), an IL-6 class cytokine, is reported to be antiatherosclerotic. Thus, we hypothesized that LIF expression might be altered during in-stent neointimal hyperplasia. Ossabaw miniature swine, a unique large-animal model of metabolic syndrome and cardiovascular disease, were used for these studies. Bare-metal stents were deployed in the left anterior descending and left circumflex coronary arteries. Stents were expanded to either 1.0 x luminal diameter (in accordance with current clinical practice) or 1.3 x (overexpansion). The development of in-stent neointimal hyperplasia was assessed 28-day postimplantation using intravascular ultrasound. The atherosclerotic coverage of the vessel wall was approximately five-fold higher in 1.0 x stents and approximately nine-fold higher in 1.3 x stents 4 weeks after deployment, compared with the same segments before stenting. LIF mRNA was elevated approximately 11-fold in stented segments, relative to unstented epicardial coronary arteries. LIF expression and the intima : media ratio were strongly correlated in 1.0 x stented vessels. Further studies to investigate the nature of the association between LIF and neointimal hyperplasia revealed that vascular smooth muscle cell proliferation was inhibited by LIF treatment in an in-vitro model of atherosclerosis (coronary artery organ culture). These novel and clinically relevant studies show that elevated LIF gene expression is predictive for in-stent neointimal hyperplasia, and suggest that LIF upregulation may be a compensatory mechanism in this setting.


Asunto(s)
Reestenosis Coronaria/metabolismo , Vasos Coronarios/metabolismo , Factor Inhibidor de Leucemia/metabolismo , Animales , Reestenosis Coronaria/patología , Hiperplasia/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Técnicas de Cultivo de Órganos , Stents , Porcinos , Porcinos Enanos , Túnica Íntima/metabolismo , Túnica Íntima/patología , Regulación hacia Arriba
14.
Coron Artery Dis ; 19(1): 27-31, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18281812

RESUMEN

BACKGROUND: Stent-induced neointimal hyperplasia is a major cause of morbidity following stent deployment in patients with coronary artery disease. Importantly, however, mechanisms underlying stent-induced neointimal hyperplasia are unclear. This pathological response to stent placement is more aggressive when stents are over-expanded, suggesting that vascular injury may play a role. In this study we tested the hypothesis that adenosine A1 receptor upregulation is associated with neointimal hyperplasia within coronary artery stents. METHODS: Adult male Ossabaw swine were used as our experimental model. Neointima formation and gene expression were studied 4 weeks after coronary stents were placed at 1.0x or 1.3x luminal diameter. RESULTS: Neointima formation was observed in 1.0x stents and more than doubled in 1.3x stents, thus verifying the response to overexpansion injury. A1 receptor mRNA was increased four-fold and seven-fold in stents at 1.0x and 1.3x luminal diameter, suggesting that increased A1 receptor activity might contribute to stent-induced neointimal hyperplasia. Coronary artery organ culture model of arterial injury demonstrated A1 receptor activation increased DNA synthesis three-fold, an effect abolished by A1 receptor antagonism. CONCLUSION: Our data indicate that A1 receptor expression is increased within stents and that activation of A1 receptors increases smooth muscle cell proliferation. We suggest that inhibition of A1 receptor signaling may be a promising therapeutic target for management of in-stent stenosis.


Asunto(s)
Oclusión de Injerto Vascular/patología , Receptor de Adenosina A1/genética , Receptor de Adenosina A1/metabolismo , Stents , Túnica Íntima/patología , Animales , Expresión Génica , Oclusión de Injerto Vascular/diagnóstico por imagen , Hiperplasia , Masculino , Porcinos , Porcinos Enanos , Túnica Íntima/diagnóstico por imagen , Ultrasonografía Intervencional
15.
Biol Psychol ; 133: 85-88, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29427602

RESUMEN

Tear secretory immunoglobulin-A (SIgA) is a putative biomarker of common-cold risk with potential utility in non-invasive diagnostics. As SIgA secretion at the ocular surface is under strong autonomic control, we investigated the relationship between HR reactivity and tear SIgA responses to novel experiential stress. Thirty-two healthy participants undertook a 60 s zip-line ride to evoke acute stress and a seated-rest control trial in a randomised-crossover design. We recorded heart rate (HR) continuously and collected unstimulated tear samples 5 min pre-, 2 min post- and 20 min post-stress/control. Stress increased HR and state anxiety whereas tear SIgA concentration decreased 44% post-stress vs. CONTROL: Higher peak HR values during stress uniquely explained 21% of the variance in tear SIgA reactivity to stress (p < 0.01); high HR reactors displayed greater decreases in tear SIgA concentration. We conclude that physiological arousal increases immune reactivity to acute stress and highlight tear SIgA as a minimally-invasive, physiologically relevant biomarker of immune reactivity.


Asunto(s)
Frecuencia Cardíaca/fisiología , Inmunoglobulina A Secretora/metabolismo , Estrés Fisiológico/fisiología , Lágrimas/química , Adulto , Sistema Nervioso Autónomo , Biomarcadores/metabolismo , Estudios Cruzados , Femenino , Humanos , Masculino , Adulto Joven
16.
Brachytherapy ; 16(2): 393-401, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28139423

RESUMEN

PURPOSE: Optimal curative intent brachytherapy for certain gynecologic cancers requires interstitial brachytherapy, often using template-guided techniques such as a Syed-Neblett implant. Whether high or low dose rate (LDR), these procedures pose significant risks to patients, partly attributable to the prolonged period of bed rest. Published results of free-handed permanent interstitial brachytherapy (PIB) with 131Cs demonstrate it to be an effective modality for the management of small volume gynecologic cancers. This report is the first to describe a permanent template-guided interstitial technique using 131Cs for gynecologic cancers, performed as an LDR outpatient procedure. METHODS AND MATERIALS: Five sequential patients with recurrent or primary gynecologic malignancies underwent template-guided PIB using 131Cs. A posttreatment planning CT was obtained immediately after the procedure and again 3-4 weeks later. Both CT data sets were fused and the relative positions compared to assess for migration in the x, y, and z planes. Seed positions as well as dosimetric parameters including D90, D100, V100, and the dose to 2 cc of rectum and bladder were compared to quantify migration of sources and the resulting effect, if any, on the treatment. RESULTS: The median age was 69 years (range 64-85). All patients received a template-guided 131Cs PIB implant to treat gross disease. All 5 patients had significant medical comorbidities that limited treatment options. Considering all 5 patients, a total of 40 interstitial needles were placed. Ten needles carried only Vicryl-stranded sources, and 30 needles carried a combination of stranded 131Cs seeds and free seeds. Needle count was between 6 and 10 needles per patient, with active lengths of 4-10 cm. The median dose was 30 Gy (range 25-55 Gy) to permanent decay, enabling a cumulative median biological effective dose 91.5 Gy (range 60.9-92.1 Gy) and equivalent dose at 2 Gy per fraction 75.9 Gy (range 50.7-76.8 Gy). All implants were performed as outpatient procedures with only the first patient admitted for 23-hour observation. All calculated median migration distances were less than 1 cm in the axial, sagittal, or coronal planes. In 69.2% cases, the individual seed migration was <5 mm. Strand migration appeared directly related to peripheral placement and the use of stranded sources. The median D90, D100, and V100 were compared between study sets, and no significant differences were identified. No Grade 3 or higher complications occurred. CONCLUSIONS: Permanent LDR template-guided PIB using 131Cs can be safely performed on an outpatient basis. Compared to currently used template-guided techniques, the use of 131Cs avoids prolonged bed rest and hospitalization, significantly lowers cost, and enables a higher cumulative dose. Seed migration is minimal with this technique. Early experience suggests that the technique is safe and merits further study.


Asunto(s)
Braquiterapia/métodos , Radioisótopos de Cesio/uso terapéutico , Neoplasias de los Genitales Femeninos/radioterapia , Anciano , Anciano de 80 o más Años , Atención Ambulatoria , Femenino , Humanos , Persona de Mediana Edad , Agujas , Prótesis e Implantes , Radiometría , Dosificación Radioterapéutica , Recto , Vejiga Urinaria
17.
Int J Radiat Oncol Biol Phys ; 99(5): 1225-1233, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-29029888

RESUMEN

PURPOSE: To present a time-to-failure (TTF) analysis for all patients treated with permanent interstitial brachytherapy (PIB) at our institution, with additional analyses to correlate successful reirradiation and to identify the frequency of severe grade 3 to 4 toxicity. METHODS AND MATERIALS: Forty-two previously irradiated patients received curative or palliative intent PIB for a recurrent pelvic malignancy between January 2009 and August 2016. Minimum follow-up was 6 months after the PIB procedure. All patients had a biopsy-proven recurrence and were treated using PIB alone (n=32) or in combination with a short course of additional radiation therapy (n=10). Competing risk analyses were performed to assess the risk of failures in the presence of death without failure. Exploratory analyses were performed for factors related to failure using competing risk analyses and the Gray statistic. RESULTS: A total of 61 PIB implants were performed among 42 patients with a median follow-up of 16.3 months. Fifty-two implants were performed as the first salvage reirradiation to a solitary recurrence (8 patients had more than 1 lesion); the success rate for initial reirradiation using PIB was 73% (38 cases out of 52), and the median TTF was not reached. Nine patients underwent a second repeat PIB to the same recurrence as a form of salvage; 3 (33%) remain without evidence of recurrence. The median TTF after second salvage was 7.7 months. Even with the limited sample size, prolonged TTF was marginally associated with definitive intent (P=.07) and the extent of disease at the time of PIB (P=.08). Grade 3+ toxicities were seen in 8 patients (16.7%). CONCLUSIONS: Permanent interstitial brachytherapy is a feasible and potentially durable treatment modality that can be used to curatively salvage selected recurrent pelvic malignancies in a previously irradiated field.


Asunto(s)
Braquiterapia/métodos , Neoplasias de los Genitales Femeninos/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Neoplasias Pélvicas/radioterapia , Reirradiación/métodos , Terapia Recuperativa/métodos , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia/efectos adversos , Radioisótopos de Cesio/uso terapéutico , Femenino , Radioisótopos de Oro/uso terapéutico , Humanos , Persona de Mediana Edad , Traumatismos por Radiación/patología , Planificación de la Radioterapia Asistida por Computador/métodos , Reirradiación/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa/efectos adversos , Factores de Tiempo , Insuficiencia del Tratamiento
18.
J Am Acad Audiol ; 17(2): 133-40, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16640065

RESUMEN

The purpose of this investigation was to determine the impact of commonly recommended cochlear implant (CI) speech processor placements on microphone output both with and without single channel front-end compression. The impact of this compression use on interaural level difference (ILD) magnitude was also evaluated for the ear-level position. Finally, pilot localization data collected with and without single channel front-end compression was collected on seven bilateral cochlear implant recipients. The results revealed that differences in signal audibility due to clinical placement of CI speech processors in ear, shoulder, and collar positions can at least partially be offset through the use of front-end compression. These data also revealed that compression impacted ILD cues. Preliminary data indicated that some bilaterally implanted subjects were able to take advantage of the enhanced ILD cues when compression was turned off, while other bilaterally implanted subjects did not localize better in the compression-off condition.


Asunto(s)
Percepción Auditiva/fisiología , Implantes Cocleares , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/rehabilitación , Localización de Sonidos/fisiología , Estimulación Acústica , Adulto , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad
19.
Traffic Inj Prev ; 17(5): 480-7, 2016 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-26506986

RESUMEN

OBJECTIVES: Studies from different parts of the world have indicated that the impact of road traffic incidents disproportionally affects young adults. Few known studies have been forthcoming from Arabian Gulf countries. Within Oman, a high proportion of the population is under the age of 20. Coupled with the drastic increase in motorization in recent years, there is a need to understand the state of road safety among young people in Oman. The current research aimed to explore the prevalence and characteristics of road traffic injuries among young drivers aged 17-25 years. METHODS: Crash data from 2009 to 2011 were extracted from the Directorate General of Traffic, Royal Oman Police (ROP) database in Oman. The data were analyzed to explore the impact of road crashes on young people (17-25 years), the characteristics of young driver crashes, and how these differ from older drivers and to identify key predictors of fatalities in young driver crashes. RESULTS: Overall, young people were overrepresented in injuries and fatalities within the sample time period. Though it is true that many young people in crashes were driving at the time, it was also evident that young people were often victims in a crash caused by someone else. Thus, to reduce the impact of road crashes on young people, there is a need to generally address road safety within Oman. When young drivers were involved in crashes they were predominantly male. The types of crashes these drivers have can be broadly attributed to risk taking and inexperience. Speeding and nighttime driving were the key risk factors for fatalities. CONCLUSION: The results highlight the need to address young driver safety in Oman. From these findings, the introduction of a graduated driver licensing system with nighttime driving restrictions could significantly improve young driver safety.


Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Adolescente , Adulto , Conducción de Automóvil/legislación & jurisprudencia , Conducción de Automóvil/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Humanos , Concesión de Licencias , Masculino , Omán/epidemiología , Policia , Prevalencia , Factores de Riesgo , Seguridad , Adulto Joven
20.
Med Sci Sports Exerc ; 48(3): 569-77, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26496418

RESUMEN

PURPOSE: Research has not convincingly demonstrated the utility of saliva secretory immunoglobulin-A (SIgA) as a biomarker of upper respiratory tract infection (URTI) risk, and disagreement exists about the influence of heavy exercise ("open-window theory") and dehydration on saliva SIgA. Prompted by the search for viable alternatives, we compared the utility of tear and saliva SIgA to predict URTI prospectively (study 1) and assessed the influence of exercise (study 2) and dehydration (study 3) using a repeated-measures crossover design. METHODS: In study 1, 40 subjects were recruited during the common-cold season. Subjects provided tear and saliva samples weekly and recorded upper respiratory symptoms (URS) daily for 3 wk. Real-time PCR confirmed common-cold pathogens in 9 of 11 subjects reporting URS (82%). Predictive utility of tear and saliva SIgA was explored by comparing healthy samples with those collected during the week before URS. In study 2, 13 subjects performed a 2-h run at 65% V˙O2peak. In study 3, 13 subjects performed exercise heat stress to 3% body mass loss followed by overnight fluid restriction. RESULTS: Tear SIgA concentration and secretion rate were 48% and 51% lower, respectively, during URTI and 34% and 46% lower the week before URS (P < 0.05), but saliva SIgA remained unchanged. The risk of URS the following week increased ninefold (95% confidence interval, 1.7-48) when the tear SIgA secretion rate was <5.5 µg·min(-1) and sixfold (95% confidence interval, 1.2-29) when the tear SIgA secretion rate decreased >30%. Tear SIgA secretion rate >5.5 µg·min(-1) or no decrease of >30% predicted subjects free of URS in >80% of cases. Tear SIgA concentration decreased after exercise (-57%, P < 0.05) in line with the "open-window theory" but was unaffected by dehydration. Saliva flow rate decreased and saliva SIgA concentration increased after exercise and during dehydration (P < 0.05). CONCLUSIONS: Tear SIgA has utility as a noninvasive biomarker of mucosal immunity and common-cold risk.


Asunto(s)
Resfriado Común/diagnóstico , Deshidratación/fisiopatología , Ejercicio Físico/fisiología , Inmunidad Mucosa , Inmunoglobulina A Secretora/química , Lágrimas/química , Adolescente , Adulto , Biomarcadores/química , Estudios Cruzados , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Saliva/química , Adulto Joven
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