Publications by authors named "Alexander M Gorbach"

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 on a blood smear, a Blantyre coma score of 2 or less, and retinopathy.

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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.

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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.

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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 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Background: Human obesity is associated with increased heat production; however, subcutaneous adipose tissue provides an insulating layer that impedes heat loss. To maintain normothermia, therefore, obese individuals must increase their heat dissipation.

Objective: The objective was to test the hypothesis that temperature in a heat-dissipating region of the hand is elevated in obese adults.

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Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and resistance (R). We investigated infrared (IR) imaging during PP as a means for precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr of PP in an uncontrolled Donation after Cardiac Death model.

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A high-resolution infrared (IR) camera was used to assess rhythmicity in localized renal blood flow, including the extent of regions containing nephrons with spontaneous oscillations in their individual blood flow. The IR imaging was able to follow changes in rat renal perfusion during baseline conditions, during occlusion of the main renal artery and during the administration of either saline or papaverine. Concurrent recordings were made of tubular pressure in superficial nephrons.

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Background: Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfusion of brain tumors and kidneys during human surgery. Intraoperative IR imaging has the potential for more objective real-time detection and quantitative assessment of organ viability including early ischemia.

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Background: Intraoperative cholangiograms (IOCs) may increase cost, surgical time, and radiation exposure of staff and patients. The authors introduce the application of passive infrared imaging to intraoperative cholangiography as a feasible alternative to traditional fluoroscopic IOCs.

Methods: A porcine model was used in which the gallbladder, cystic duct, common bile duct (CBD), and duodenum were exposed and an 18-gauge angiocatheter was inserted into the cystic duct.

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Object: Although clinical imaging defines the anatomical relationship between a brain tumor and the surrounding brain and neurological deficits indicate the neurophysiological consequences of the tumor, the effect of a brain tumor on vascular physiology is less clear.

Methods: An infrared camera was used to measure the temperature of the cortical surface before, during, and after removal of a mass in 34 patients (primary brain tumor in 21 patients, brain metastases in 10 and falx meningioma, cavernous angioma, and radiation necrosis-astrocytosis in one patient each). To establish the magnitude of the effect on blood flow induced by the tumor, the images were compared with those from a group of six patients who underwent temporal lobectomy for epilepsy.

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We hypothesized that it would be possible to detect the distribution of cortical activation by using a sensitive, rapid, high-resolution infrared imaging technique to monitor changes in local cerebral blood flow induced by changes in focal cortical metabolism. In a prospective study, we recorded in 21 patients the emission of infrared radiation from the exposed human cerebral cortex at baseline, during language and motor tasks, and during stimulation of the contralateral median nerve using an infrared camera (sensitivity 0.02 degrees C).

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