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1.
Sci Transl Med ; 15(713): eadh4293, 2023 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-37703350

RESUMEN

Brain swelling is associated with death from cerebral malaria, but it is unclear whether brain swelling is caused by cerebral edema or vascular congestion-two pathological conditions with distinct effects on tissue hemoglobin concentrations. We used near-infrared spectroscopy (NIRS) to noninvasively study cerebral microvascular hemoglobin concentrations in 46 Malawian children with cerebral malaria. Cerebral malaria was defined by the presence of the malaria parasite Plasmodium falciparum on a blood smear, a Blantyre coma score of 2 or less, and retinopathy. Children with uncomplicated malaria (n = 33) and healthy children (n = 29) were enrolled as comparators. Cerebral microvascular hemoglobin concentrations were higher among children with cerebral malaria compared with those with uncomplicated malaria [median (25th, 75th): 145.2 (95.2, 190.0) µM versus 82.9 (65.7, 105.4) µM, P = 0.008]. Cerebral microvascular hemoglobin concentrations correlated with brain swelling score determined by MRI (r = 0.37, P = 0.03). Fluctuations in cerebral microvascular hemoglobin concentrations over a 30-min time period were characterized using detrended fluctuation analysis (DFA). DFA determined self-similarity of the cerebral microvascular hemoglobin concentration signal to be lower among children with cerebral malaria compared with those with uncomplicated malaria [0.63 (0.54, 0.70) versus 0.91 (0.82, 0.94), P < 0.0001]. The lower self-similarity of the hemoglobin concentration signal in children with cerebral malaria suggested impaired regulation of cerebral blood flow. The elevated cerebral tissue hemoglobin concentration and its correlation with brain swelling suggested that excess blood volume, potentially due to vascular congestion, may contribute to brain swelling in cerebral malaria.


Asunto(s)
Edema Encefálico , Malaria Cerebral , Enfermedades Vasculares , Niño , Humanos , Encéfalo , Plasmodium falciparum , Hemoglobinas
2.
JCI Insight ; 5(3)2020 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-31945019

RESUMEN

Idiopathic inflammatory myopathies (IIM) are characterized by muscle inflammation and weakness, myositis-specific autoantibodies (MSAs), and extramuscular organ damage. The role of neutrophil dysregulation and neutrophil extracellular traps (NETs) in IIM is unclear. We assessed whether pathogenic neutrophil subsets (low-density granulocytes [LDGs]) and NETs were elevated in IIM, associated with clinical presentation and MSAs, and their effect on skeletal myoblasts and myotubes. Circulating NETs and LDGs were quantified and correlated with clinical measures. Specific MSAs were tested for their ability to induce NETs. NETs and neutrophil gene expression were measured in IIM biopsies. Whether NETs damage skeletal myoblasts and myotubes was tested. Circulating LDGs and NETs were increased in IIM. IIM LDGs had an enhanced ability to form NETs. LDGs and NETs correlated with IIM disease activity and muscle damage. The serum MSA anti-MDA5 correlated with circulating and tissue NETs and directly enhanced NET formation. An enhanced neutrophil gene signature was present in IIM muscle and associated with muscle injury and tissue IFN gene signatures. IIM NETs decreased the viability of myotubes in a citrullinated histone-dependent manner. Dysregulated neutrophil pathways may play pathogenic roles in IIM through their ability to directly injure muscle cells and other affected tissues.


Asunto(s)
Miositis/sangre , Neutrófilos/inmunología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Trampas Extracelulares/inmunología , Humanos , Miositis/inmunología
3.
Interact J Med Res ; 8(1): e10336, 2019 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-30609977

RESUMEN

BACKGROUND: Patient journals have been used as valuable resources in clinical studies. However, the full potential value of such journals can be undermined by inefficiencies and ambiguities associated with handwritten patient reports. The increasing number of mobile phones and mobile-based health care approaches presents an opportunity to improve communications from patients to clinicians and clinical researchers through the use of digital patient journals. OBJECTIVE: The objective of this project was to develop a smartphone-based platform that would enable patients to record events and symptoms on the same timeline as clinical data collected by wearable sensors. METHODS: This platform consists of two major components: a smartphone for patients to record their journals and wireless sensors for clinical data collection. The clinical data and patient records are then exported to a clinical researcher interface, and the data and journal are processed and combined into a single time-series graph for analysis. This paper gives a block diagram of the platform's principal components and compares its features to those of other methods but does not explicitly discuss the process of design or development of the system. RESULTS: As a proof of concept, body temperature data were obtained in a 4-hour span from a 22-year-old male, during which the subject simultaneously recorded relevant activities and events using the iPhone platform. After export to a clinical researcher's desktop, the digital records and temperature data were processed and fused into a single time-series graph. The events were filtered based on specific keywords to facilitate data analysis. CONCLUSIONS: We have developed a user-friendly patient journal platform, based on widely available smartphone technology, that gives clinicians and researchers a simple method to track and analyze patient activities and record the activities on a shared timeline with clinical data from wearable devices.

4.
Front Cell Neurosci ; 11: 298, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28993725

RESUMEN

The present study was aimed to in vivo assess the blood flow oscillatory patterns in rat pial microvessels during 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion by laser speckle imaging (LSI). Pial microcirculation was visualized by fluorescence microscopy. The blood flow oscillations of single microvessels were recorded by LSI; spectral analysis was performed by Wavelet transform. Under baseline conditions, arterioles and venules were characterized by blood flow oscillations in the frequency ranges 0.005-0.0095 Hz, 0.0095-0.021 Hz, 0.021-0.052 Hz, 0.052-0.150 Hz and 0.150-0.500 Hz. Arterioles showed oscillations with the highest spectral density when compared with venules. Moreover, the frequency components in the ranges 0.052-0.150 Hz and 0.150-0.500 were predominant in the arteriolar total power spectrum; while, the frequency component in the range 0.150-0.500 Hz showed the highest spectral density in venules. After 30 min BCCAO, the arteriolar spectral density decreased compared to baseline; moreover, the arteriolar frequency component in the range 0.052-0.150 Hz significantly decreased in percent spectral density, while the frequency component in the range 0.150-0.500 Hz significantly increased in percent spectral density. However, an increase in arteriolar spectral density was detected at 60 min reperfusion compared to BCCAO values; consequently, an increase in percent spectral density of the frequency component in the range 0.052-0.150 Hz was observed, while the percent spectral density of the frequency component in the range 0.150-0.500 Hz significantly decreased. The remaining frequency components did not significantly change during hypoperfusion and reperfusion. The changes in blood flow during hypoperfusion/reperfusion caused tissue damage in the cortex and striatum of all animals. In conclusion, our data demonstrate that the frequency component in the range 0.052-0.150 Hz, related to myogenic activity, was significantly impaired by hypoperfusion and reperfusion, affecting cerebral blood flow distribution and causing tissue damage.

5.
Sci Adv ; 1(9): e1500701, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26601309

RESUMEN

Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities.

6.
Quant Infrared Thermogr J ; 12(2): 173-183, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26435756

RESUMEN

Continuous infrared imaging revealed transient changes in forearm temperature during arterial occlusion, reperfusion, and recovery in a healthy subject group. Processing the imaging data with the k-means algorithm further revealed reactive vascular sites in the skin with rapid or delayed temperature amplification. The observed temporal and spatial diversity of blood-flow-derived forearm temperature allow consideration of thermal-imaging guided placement of skin sensors to achieve enhanced sensitivity in monitoring of skin hemodynamics.

8.
ACS Nano ; 8(5): 4177-89, 2014 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-24708375

RESUMEN

Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells. The novel nanoformula with a cholanic acid-derivatized hyaluronic acid (CAHA) biopolymer wrapped around a sSWCNT and loaded with doxorubicin (DOX), CAHA-sSWCNT-DOX, is much more effective in killing drug-resistant cancer cells compared to the free DOX and phospholipid PEG (PL-PEG)-modified sSWCNT formula, PEG-sSWCNT-DOX. The CAHA-sSWCNT-DOX affects the viscoelastic property more than free DOX and PL-PEG-sSWCNT-DOX, which in turn allows more drug molecules to be internalized. Intravenous injection of CAHA-sSWCNT-DOX (12 mg/kg DOX equivalent) followed by 808 nm laser irradiation (1 W/cm(2), 90 s) led to complete tumor eradication in a subcutaneous OVCAR8/ADR drug-resistant xenograft model, while free DOX alone failed to delay tumor growth. Our newly developed CAHA-sSWCNT-DOX nanoformula, which delivers therapeutics and acts as a sensitizer to influence drug uptake and induce apoptosis with minimal resistance factor, provides a novel effective means of counteracting the phenomenon of multidrug resistance.


Asunto(s)
Resistencia a Antineoplásicos , Nanotecnología/métodos , Nanotubos/química , Neoplasias/tratamiento farmacológico , Animales , Apoptosis , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Resistencia a Múltiples Medicamentos , Elasticidad , Femenino , Humanos , Ratones , Ratones SCID , Nanotubos de Carbono/química , Neoplasias/patología , Fosfolípidos/química , Polietilenglicoles/química , Polímeros/química , Tecnicas de Microbalanza del Cristal de Cuarzo , Semiconductores , Temperatura , Viscosidad
9.
Blood ; 123(20): 3101-4, 2014 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-24665133

RESUMEN

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.


Asunto(s)
Dolor Agudo/complicaciones , Anemia de Células Falciformes/complicaciones , Arteriopatías Oclusivas/complicaciones , Arteria Braquial/patología , Microvasos/patología , Consumo de Oxígeno , Dolor Agudo/metabolismo , Dolor Agudo/patología , Adulto , Anemia de Células Falciformes/metabolismo , Anemia de Células Falciformes/patología , Arteriopatías Oclusivas/metabolismo , Arteriopatías Oclusivas/patología , Arteria Braquial/metabolismo , Femenino , Humanos , Inflamación/complicaciones , Masculino , Microvasos/metabolismo , Persona de Mediana Edad , Oxígeno/metabolismo , Dolor
10.
Chronobiol Int ; 31(3): 409-20, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24397341

RESUMEN

The disruption of the temperature circadian rhythm has been associated with cancer progression, while its amplification resulted in cancer inhibition in experimental tumor models. The current study investigated the relevance of skin surface temperature rhythms as biomarkers of the Circadian Timing System (CTS) in order to optimize chronotherapy timing in individual cancer patients. Baseline skin surface temperature at four sites and wrist accelerations were measured every minute for 4 days in 16 patients with metastatic gastro-intestinal cancer before chronotherapy administration. Temperature and rest-activity were recorded, respectively, with wireless skin surface temperature patches (Respironics, Phillips) and an actigraph (Ambulatory Monitoring). Both variables were further monitored in 10 of these patients during and after a 4-day course of a fixed chronotherapy protocol. Collected at baseline, during and after therapy longitudinal data sets were processed using Fast Fourier Transform Cosinor and Linear Discriminant Analyses methods. A circadian rhythm was statistically validated with a period of 24 h (p < 0.05) for 49/61 temperature time series (80.3%), and 15/16 rest-activity patterns (93.7%) at baseline. However, individual circadian amplitudes varied from 0.04 °C to 2.86 °C for skin surface temperature (median, 0.72 °C), and from 16.6 to 146.1 acc/min for rest-activity (median, 88.9 acc/min). Thirty-nine pairs of baseline temperature and rest-activity time series (75%) were correlated (r > |0.7|; p < 0.05). Individual circadian acrophases at baseline were scattered from 15:18 to 6:05 for skin surface temperature, and from 12:19 to 15:18 for rest-activity, with respective median values of 01:10 (25-75% quartiles, 22:35-3:07) and 14:12 (13:14-14:31). The circadian patterns in skin surface temperature and rest-activity persisted or were amplified during and after fixed chronotherapy delivery for 5/10 patients. In contrast, transient or sustained disruption of these biomarkers was found for the five other patients, as indicated by the lack of any statistically significant dominant period in the circadian range. No consistent correlation (r < |0.7|, p ≥ 0.05) was found between paired rest-activity and temperature time series during fixed chronotherapy delivery. In conclusion, large inter-patient differences in circadian amplitudes and acrophases of skin surface temperature were demonstrated for the first time in cancer patients, despite rather similar rest-activity acrophases. The patient-dependent coupling between both CTS biomarkers, and its possible alteration on a fixed chronotherapy protocol, support the concept of personalized cancer chronotherapy.


Asunto(s)
Cronoterapia , Ritmo Circadiano/fisiología , Neoplasias/terapia , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Cronoterapia/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Temperatura Cutánea , Vértebras Torácicas/fisiología
11.
Am J Hematol ; 89(1): 1-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23963836

RESUMEN

Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Úlcera de la Pierna/etiología , Úlcera de la Pierna/patología , Piel/irrigación sanguínea , Adulto , Biopsia , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/patología , Úlcera de la Pierna/diagnóstico , Masculino , Microcirculación , Persona de Mediana Edad , Flujo Sanguíneo Regional , Factores de Riesgo , Termografía
12.
Lancet Haematol ; 1(3): e95-e103, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25938131

RESUMEN

BACKGROUND: Well-tolerated and effective treatments are needed for chronic leg ulcers in sickle cell anaemia. Topical sodium nitrite, a known nitric oxide donor, enhances blood flow in ulcers and has known bacteriostatic effects. We aimed to assess the safety, tolerability, and pharmacokinetics of topical sodium nitrite in patients with sickle cell disease and chronic leg ulcers. METHODS: We enrolled adult patients from an ambulatory clinic at the National Institutes of Health (Bethesda, MD, USA) with sickle cell anaemia with leg ulcers (with a surface area of 2.5-100 cm2) persisting for at least 4 weeks into a safety and tolerability phase 1 dose-escalation trial of topical sodium nitrite. Increasing concentrations of sodium nitrite cream were applied twice weekly for 4 weeks to one ulcer per patient at five dose levels (0.5%, 1%, 1.5%, 1.8%, and 2%). The primary endpoints were safety and tolerability, with secondary endpoints of pharmacokinetics, blood flow, and wound healing. Pain relief was analysed post hoc. Endpoints were analysed over time for the whole study population and according to dose level. This study is registered with ClinicalTrials.gov, number NCT01316796. FINDINGS: Between April 4, 2011, and March 19, 2013, we enrolled 18 adult patients with sickle cell anaemia and leg ulcers into our trial. We assigned three patients into each cohort, and each cohort was treated with a different concentration of sodium nitrite cream (cohort 1: 0.5%, cohort 2: 1.0%, cohort 3: 1.5%, and cohort 4: 2.0%). Patients were not enrolled into the next cohort dose until we were able to establish that no dose-limiting toxicities were observed. An additional six patients were enrolled to cohort 3a: 1.8%, after two patients in cohort 4 had asymptomatic drops in diastolic blood pressure. No grade 3-4 adverse events were observed, and there were no serious adverse events or dose-limiting side-effects. Pharmacokinetic analysis showed that systemic absorption of sodium nitrite was very low. Application of topical sodium nitrite was associated with a significant increase in peri-wound cutaneous blood flow measured by laser speckle contrast imaging (p=0.0002), corroborated by increased peri-wound skin temperature by infrared thermography (p=0.0119). We recorded a dose-dependent decrease in leg ulcer size (p=0.0012) and pain (p<0.0001). Ulcers healed completely in three patients who received the highest concentrations of topical sodium nitrite (the 1.8% and 2% cream). In our post-hoc analysis of pain, brief pain inventory scores improved in pain severity (p=0.0048) and pain interference (p=0.0013). INTERPRETATION: Our results indicate that topical sodium nitrite 2% cream is suitable for additional clinical trials in adults with sickle cell anaemia to promote healing of leg ulcers. FUNDING: National Heart, Lung and Blood Institute Division of Intramural Research (National Institutes of Health).

13.
Nat Mater ; 12(10): 938-44, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24037122

RESUMEN

Precision thermometry of the skin can, together with other measurements, provide clinically relevant information about cardiovascular health, cognitive state, malignancy and many other important aspects of human physiology. Here, we introduce an ultrathin, compliant skin-like sensor/actuator technology that can pliably laminate onto the epidermis to provide continuous, accurate thermal characterizations that are unavailable with other methods. Examples include non-invasive spatial mapping of skin temperature with millikelvin precision, and simultaneous quantitative assessment of tissue thermal conductivity. Such devices can also be implemented in ways that reveal the time-dynamic influence of blood flow and perfusion on these properties. Experimental and theoretical studies establish the underlying principles of operation, and define engineering guidelines for device design. Evaluation of subtle variations in skin temperature associated with mental activity, physical stimulation and vasoconstriction/dilation along with accurate determination of skin hydration through measurements of thermal conductivity represent some important operational examples.


Asunto(s)
Temperatura Cutánea , Termometría/instrumentación , Adulto , Epidermis/fisiología , Humanos , Masculino , Procesos Mentales/fisiología , Estimulación Física , Descanso , Factores de Tiempo
14.
PLoS One ; 8(2): e56773, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23451084

RESUMEN

BACKGROUND: While a number of the consequences of mast cell degranulation within tissues have been documented including tissue-specific changes such as bronchospasm and the subsequent cellular infiltrate, there is little known about the immediate effects of mast cell degranulation on the associated vasculature, critical to understanding the evolution of mast cell dependent inflammation. OBJECTIVE: To characterize the microcirculatory events that follow mast cell degranulation. METHODOLOGY/PRINCIPAL FINDINGS: Perturbations in dermal blood flow, temperature and skin color were analyzed using laser-speckle contrast imaging, infrared and polarized-light colorimetry following cold-hand immersion (CHI) challenge in patients with cold-induced urticaria compared to the response in healthy controls. Evidence for mast cell degranulation was established by documentation of serum histamine levels and the localized release of tryptase in post-challenge urticarial biopsies. Laser-speckle contrast imaging quantified the attenuated response to cold challenge in patients on cetirizine. We found that the histamine-associated vascular response accompanying mast cell degranulation is rapid and extensive. At the tissue level, it is characterized by a uniform pattern of increased blood flow, thermal warming, vasodilation, and recruitment of collateral circulation. These vascular responses are modified by the administration of an antihistamine. CONCLUSIONS/SIGNIFICANCE: Monitoring the hemodynamic responses within tissues that are associated with mast cell degranulation provides additional insight into the evolution of the acute inflammatory response and offers a unique approach to assess the effectiveness of treatment intervention.


Asunto(s)
Degranulación de la Célula/fisiología , Frío , Mastocitos/metabolismo , Mastocitos/patología , Urticaria/fisiopatología , Adolescente , Adulto , Anciano , Degranulación de la Célula/efectos de los fármacos , Niño , Preescolar , Femenino , Histamina/metabolismo , Antagonistas de los Receptores Histamínicos/farmacología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional/efectos de los fármacos , Piel/efectos de los fármacos , Piel/patología , Triptasas/sangre , Adulto Joven
15.
Microvasc Res ; 84(3): 262-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22784510

RESUMEN

Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1°C, p<0.0001) and SNP (+0.9°C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2°C, 6.0±0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R(2)=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD.


Asunto(s)
Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/patología , Óxido Nítrico/metabolismo , Espectrofotometría Infrarroja/métodos , Acetilcolina/metabolismo , Adulto , Velocidad del Flujo Sanguíneo , Relación Dosis-Respuesta a Droga , Ecocardiografía/métodos , Endotelio Vascular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/metabolismo , Análisis de Regresión , Riesgo , Temperatura Cutánea , omega-N-Metilarginina/farmacología
16.
IEEE Trans Biomed Eng ; 59(2): 303-6, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21803676

RESUMEN

We show that a mobile phone can serve as an accurate monitor for several physiological variables, based on its ability to record and analyze the varying color signals of a fingertip placed in contact with its optical sensor. We confirm the accuracy of measurements of breathing rate, cardiac R-R intervals, and blood oxygen saturation, by comparisons to standard methods for making such measurements (respiration belts, ECGs, and pulse-oximeters, respectively). Measurement of respiratory rate uses a previously reported algorithm developed for use with a pulse-oximeter, based on amplitude and frequency modulation sequences within the light signal. We note that this technology can also be used with recently developed algorithms for detection of atrial fibrillation or blood loss.


Asunto(s)
Teléfono Celular , Monitoreo Fisiológico/instrumentación , Tecnología de Sensores Remotos/instrumentación , Procesamiento de Señales Asistido por Computador , Algoritmos , Frecuencia Cardíaca/fisiología , Humanos , Monitoreo Fisiológico/métodos , Oximetría/instrumentación , Frecuencia Respiratoria/fisiología
17.
Quant Infrared Thermogr J ; 9(2): 123-133, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23667389

RESUMEN

Thermal representations on the surface of a human forearm of underlying perforator vessels have previously been mapped via recovery-enhanced infrared imaging, which is performed as skin blood flow recovers to baseline levels following cooling of the forearm. We noted that the same vessels could also be observed during reactive hyperaemia tests after complete 5-min occlusion of the forearm by an inflatable cuff. However, not all subjects showed vessels with acceptable contrast. Therefore, we applied a thermographic signal reconstruction algorithm to reactive hyperaemia testing, which substantially enhanced signal-to-noise ratios between perforator vessels and their surroundings, thereby enabling their mapping with higher accuracy and a shorter occlusion period.

18.
Interface Focus ; 1: 48-60, 2011 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-21544221

RESUMEN

Chronotherapeutics involve the administration of treatments according to circadian rhythms. Circadian timing of anti-cancer medications has been shown to improve treatment tolerability up to fivefold and double efficacy in experimental and clinical studies. However, the physiological and the molecular components of the circadian timing system (CTS), as well as gender, critically affect the success of a standardized chronotherapeutic schedule. In addition, a wrongly timed therapy or an excessive drug dose disrupts the CTS. Therefore, a non-invasive approach to accurately detect and monitor circadian rhythms is needed for a dynamic assessment of the CTS in order to personalize chronomodulated drug delivery schedule in cancer patients. Since core body temperature is a robust circadian biomarker, we recorded temperature at multiple locations on the skin of the upper chest and back of controls and cancer patients continuously. Variability in the circadian phase existed among patch locations in individual subjects over the course of 2-6 days, demonstrating the need to monitor multiple skin temperature locations to determine the precise circadian phase. Additionally, we observed that locations identified by infrared imaging as relatively cool had the largest 24 h temperature variations. Disruptions in skin temperature rhythms during treatment were found, pointing to the need to continually assess circadian timing and personalize chronotherapeutic schedules.

19.
Am J Clin Nutr ; 93(5): 963-7, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21367952

RESUMEN

BACKGROUND: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity. OBJECTIVE: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals. DESIGN: In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI ≥30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for ≥48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis. RESULTS: Mean (±SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 ± 0.03°C compared with 36.89 ± 0.03°C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature ≈0.23°C greater than that of men (36.99 ± 0.03°C compared with 36.76 ± 0.03°C; P < 0.0001). CONCLUSIONS: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500.


Asunto(s)
Regulación de la Temperatura Corporal , Obesidad/fisiopatología , Adulto , Índice de Masa Corporal , Temperatura Corporal , Ritmo Circadiano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Ambulatorio , Caracteres Sexuales
20.
Quant Infrared Thermogr J ; 8(1): 21-36, 2011 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23538682

RESUMEN

In this work we demonstrate that functional infrared imaging is capable of detecting low frequency temperature fluctuations in intact human skin and revealing spatial, temporal, spectral, and time-frequency based differences among three tissue classes: microvasculature, large sub-cutaneous veins, and the remaining surrounding tissue of the forearm. We found that large veins have stronger contractility in the range of 0.005-0.06 Hz compared to the other two tissue classes. Wavelet phase coherence and power spectrum correlation analysis show that microvasculature and skin areas without vessels visible by IR have high phase coherence in the lowest three frequency ranges (0.005-0.0095 Hz, 0.0095-0.02 Hz, and 0.02-0.06 Hz), whereas large veins oscillate independently.

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