Distribution by Scientific Domains
Distribution within Medical Sciences

Selected Abstracts

The Relationship of Phthalocyanine 4 (Pc 4) Concentrations Measured Noninvasively to Outcome of Pc 4 Photodynamic Therapy in Mice

Lihua Bai
The ability to noninvasively measure photosensitizer concentration at target tissues will allow optimization of photodynamic therapy (PDT) and could improve outcome. In this study, we evaluated whether preirradiation tumor phthalocyanine 4 (Pc 4) concentrations, measured noninvasively by the optical pharmacokinetic system (OPS), correlated with tumor response to PDT. Mice bearing human breast cancer xenografts were treated with 2 mg kg,1 Pc 4 iv only, laser irradiation (150 J cm,2) only, Pc 4 followed by fractionated irradiation or Pc 4 followed by continuous irradiation. Laser irradiation treatment was initiated when the tumor to skin ratio of Pc 4 concentration reached a maximum of 2.1 at 48 h after administration. Pc 4 concentrations in tumor, as well as in Intralipid in vitro, decreased monoexponentially with laser fluence. Pc 4-PDT resulted in significant tumor regression, and tumor response was similar in the groups receiving either fractionated or continuous irradiation treatment after Pc 4. Tumor growth delay following Pc 4-PDT correlated with OPS-measured tumor Pc 4 concentrations at 24 h prior to PDT (R2 = 0.86). In excised tumors, OPS-measured Pc 4 concentrations were similar to the HPLC-measured concentrations. Thus, OPS measurements of photosensitizer concentrations can be used to assist in the scheduling of Pc 4-PDT. [source]

Dynamic study of cerebral bioenergetics and brain function using in vivo multinuclear MRS approaches

Wei Chen
Abstract One of the greatest merits of nuclear magnetic resonance (NMR) methodology used in biomedical research and clinical settings is its capability of measuring various physiological parameters in vivo. Besides MR imaging (MRI), which has been routinely applied to obtain vital information in living organs at normal and diseased states, in vivo MR spectroscopy (MRS) provides an invaluable tool for determining metabolites, chemical reaction rates, bioenergetics, and their dynamic changes in the human and animals noninvasively. These MRS capabilities are further enhanced at high/ultrahigh magnetic fields because of significant gain in NMR detection sensitivity and improvement in the spectral resolution. Recent progress has shown that in vivo MRS holds great promise in many biomedical research areas,in particular, brain research. This article provides a broad review of (i) in vivo multinuclear MRS approaches, (ii) advanced MRS methodologies, and (iii) MRS applications for determining cerebral metabolism as well as bioenergetics at resting brain state and their dynamic changes in response to brain activation. © 2005 Wiley Periodicals, Inc. Concepts Magn Reson Part A 27A: 84-121, 2005 [source]

Perfusion-based functional magnetic resonance imaging,

Afonso C. Silva
Abstract The measurement of cerebral blood flow (CBF) is a very important way of assessing tissue viability, metabolism, and function. CBF can be measured noninvasively with magnetic resonance imaging (MRI) by using arterial water as a perfusion tracer. Because of the tight coupling between neural activity and CBF, functional MRI (fMRI) techniques are having a large impact in defining regions of the brain that are activated due to specific stimuli. Among the different fMRI techniques, CBF-based fMRI has the advantages of being specific to tissue signal change, a critical feature for quantitative measurements within and across subjects, and for high-resolution functional mapping. Unlike the conventional blood oxygenation level dependent (BOLD) technique, the CBF change is an excellent index of the magnitude of neural activity change. Thus, CBF-based fMRI is the tool of choice for longitudinal functional imaging studies. A review of the principles and theoretical backgrounds of both continuous and pulsed arterial spin labeling methods for measuring CBF is presented, and a general overview of their current applications in the field of functional brain mapping is provided. In particular, examples of the use of CBF-based fMRI to investigate the fundamental hemodynamic responses induced by neural activity and to determine the signal source of the most commonly used BOLD functional imaging are reviewed. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 16A: 16,27, 2003 [source]

Linear and nonlinear measures of blood pressure variability: Increased chaos of blood pressure time series in patients with panic disorder

Vikram K. Yeragani M.B.B.S.
Abstract Arterial blood pressure (BP) variability increases progressively with the development of hypertension and an increase in BP variability is associated with end organ damage and cardiovascular morbidity. On the other hand, a decrease in heart rate (HR) variability is associated with significant cardiovascular mortality. There is a strong association between cardiovascular mortality and anxiety. Several previous studies have shown decreased HR variability in patients with anxiety. In this study, we investigated beat-to-beat variability of systolic and diastolic BP (SBP and DBP) in normal controls and patients with panic disorder during normal breathing and controlled breathing at 12, and 20 breaths per minute using linear as well as nonlinear techniques. Finger BP signal was obtained noninvasively using Finapres. Standing SBPvi and DBP BPvi (log value of BP variance corrected for mean BP divided by HR variance corrected for mean HR) were significantly higher in patients compared to controls. Largest Lyapunov exponent (LLE) of SBP and DBP, a measure of chaos, was significantly higher in patients in supine as well as standing postures. The ratios of LLE (SBP/HR) and LLE (DBP/HR) were also significantly higher (P < .001) in patients compared to controls. These findings further suggest dissociation between HR and BP variability and a possible relative increase in sympathetic function in anxiety. This increase in BP variability may partly explain the increase in cardiovascular mortality in this group of patients. Depression and Anxiety 19:85-95, 2004. © 2004 Wiley-Liss, Inc. [source]

Noninvasive Lower Eyelid Blepharoplasty: A New Technique Using Nonablative Radiofrequency on Periorbital Skin

Javier Ruiz-esparza MDArticle first published online: 3 FEB 200
Background. Laxity and rhytids of the lower eyelids are common cosmetic concerns. Historically, correction has either been surgical through either transcutaneous or transconjunctival blepharoplasty or ablative through laser resurfacing or chemical peeling. Therapeutic options usually require significant postoperative healing and have the potential risk of scarring ectropion or pigmentary loss. Objective. To report the use of a new technique that uses nonablative radiofrequency (NARF) to tighten noninvasively and nonsurgically the flaccid skin of the lower eyelids by treating the periorbital area to produce cosmetic improvement. Methods. Nine patients with skin flaccidity of the lower eyelids had a single treatment session with NARF in a small area of skin in the periorbital region, specifically the zygomatic and/or temporal areas. All patients were treated with topical anesthesia only. The treatment lasted approximately 10 minutes. No postoperative care was required. Results. All of the nine patients in the study achieved cosmetic improvement of the eyelids ostensibly through skin contraction. All patients were able to return to their normal routines immediately. Although the results were gradual, patient satisfaction was remarkable. No complications were seen in this study. Conclusion. This new procedure using NARF was successful in providing a safe, noninvasive, cosmetic improvement in these patients with excessive skin laxity of the lower eyelids. Postoperative morbidity, including down time and complications, was not seen. [source]

Noninvasive Imaging, Treatment, and Microscopic Confirmation of Clearance of Basal Cell Carcinoma

Mark Goldgeier MD
BACKGROUND. The diagnosis of basal cell carcinoma (BCC) is generally established by skin biopsy followed by tissue preparation and microscopic analysis. Treatment of BCC is often accomplished by surgical excision. Objective. To confirm the presence of BCC with a noninvasive imaging technique, to treat the patient with a topical immune response modifier, and to confirm the clearance of BCC noninvasively. METHODS. Confocal microscopy (CM) is a noninvasive technique for real-time imaging of skin in vivo. Imiquimod, an immune response modifier, is applied topically by the patient to the skin lesion. RESULTS. The presence of BCC was confirmed with CM. Posttreatment CM imaging confirmed the clearance of BCC from the entire treatment field. Both the pretreatment and the posttreatment CM findings were confirmed by invasive biopsy. CONCLUSION. The ability to use CM to image in real time without discomfort to the patient makes it a powerful tool to assist in the diagnosis of skin disease. [source]

Imaging the developing brain with fMRI

M.C. Davidson
Abstract Advancements in magnetic imaging techniques have revolutionized our ability to study the developing human brain in vivo. The ability to noninvasively image both anatomy and function in healthy volunteers, including young children, has already enhanced our understanding of brain and behavior relations. The application of these techniques to developmental research offers the opportunity to further explore these relationships and allows us to ask questions about where, when and how cognitive abilities develop in relation to changes in underlying brain systems. It is also possible to explore the contributions of maturation versus learning in the development of these abilities through cross-sectional and longitudinal research involving training and intervention procedures. Current imaging methodologies, in conjunction with new and rapidly evolving techniques, hold the promise of even greater insights into developmental issues in the near future. These methodologies and their application to development and learning are discussed in the current paper. MRDD Research Reviews 2003;9:161,167. © 2003 Wiley-Liss, Inc. [source]

Fiber tracking using magnetic resonance diffusion tensor imaging and its applications to human brain development

Richard Watts
Abstract Diffusion tensor imaging is unique in its ability to noninvasively visualize white matter fiber tracts in the human brain in vivo. Diffusion is the incoherent motion of water molecules on a microscopic scale. This motion is itself dependent on the micro-structural environment that restricts the movement of the water molecules. In white matter fibers there is a pronounced directional dependence on diffusion. With white matter fiber tracking or tractography, projections among brain regions can be detected in the three-dimensional diffusion tensor dataset according to the directionality of the fibers. Examples of developmental changes in diffusion, tracking of major fiber tracts, and examples of how diffusion tensor tractography and functional magnetic resonance imaging can be combined are provided. These techniques are complimentary and allow both the identification of the eloquent areas of the brain involved in specific functional tasks, and the connections between them. The noninvasive nature of magnetic resonance imaging will allow these techniques to be used in both longitudinal developmental and diagnostic studies. An overview of the technique and preliminary applications are presented, along with its current limitations. MRDD Research Reviews 2003;9:168,177. © 2003 Wiley-Liss, Inc. [source]

Subtle Systolic Dysfunction May Be Associated with the Tendency to Develop Diastolic Heart Failure in Patients with Preserved Left Ventricular Ejection Fraction

Hüseyin Sürücü M.D.
Background: We looked for an answer to the question of whether diastolic heart failure (DHF) is a reality or all heart failures are systolic. Method: 300 cases (hypertensive, aged, obese, etc.), not being diagnosed DHF, with preserved left ventricular (LV) ejection fraction (EF) but having the tendency to develop DHF in future were examined. One hundred and eighty cases without exclusion criteria were selected. Cases were assigned to three groups according to noninvasively obtained pulmonary capillary wedge pressure (PCWP). Results: In cases with higher PCWP (>10 mmHg), transmitral A velocity was increased (P < 0.001) and among the pulsed wave tissue Doppler imaging (pw-TDI) parameters Ea velocity was decreased (P < 0.001) and Ea-dt was prolonged (P < 0.005). In cases with lower PCWP (<8 mmHg), transmitral E velocity was higher (P< 0.001). Furthermore, a more meaningful relationship was found between PCWP and systolic pw-TDI parameters. In all the groups, it was observed that Sa velocity was progressively decreased and Q-Sa interval was progressively prolonged as PCWP increased (for all the groups P < 0.046). Conclusion: The question whether DHF is a reality or all heart failures are systolic may be answered as follows. Subtle systolic dysfunction may be associated with the tendency to develop DHF in patients with preserved LV ejection fraction. As in systolic heart failure (EF < 45%), in patients with preserved systolic function (EF , 45%), systolic and diastolic functions may impair together. The pw-TDI method may be more sensitive than standard echocardiography parameters in detection of systolic dysfunction in cases with preserved EF. [source]

Evaluation of Peripheral Vascular Endothelial Function with a Portable Ultrasound Device

Alawi A. Alsheikh-Ali M.D.
Endothelial function can be assessed noninvasively by imaging the brachial artery with ultrasound before and during reactive hyperemia. However, the standard ultrasound equipment typically used for this purpose is limited by size and expense of the machinery. In this study, we compared the ability of a portable ultrasound device to standard ultrasound equipment to visualize the brachial artery for purposes of assessing peripheral vascular endothelial function. The portable device provided comparable imaging of the brachial artery at rest and during hyperemia to that of standard ultrasound technology. These findings support the feasibility of noninvasive evaluation of peripheral endothelial function in the ambulatory setting. [source]

Proximal Isovelocity Surface Area (PISA) in the Evaluation of Fixed Membranous Subaortic Stenosis

Gregory M. Goodkin M.D.
The evaluation of the severity of subaortic stenosis is usually expressed by the magnitude of the subvalvular gradient. Calculation of the membrane orifice area noninvasively is difficult by the standard means. We present a patient in whom the area was calculated using the proximal isovelocity surface area (PISA) method. This method should have clinical applicability because it is not flow dependent and can be used in patients with normal, reduced, or increased stroke volume. [source]

Language lateralization in temporal lobe epilepsy using functional MRI and probabilistic tractography

EPILEPSIA, Issue 8 2008
Sebastian Rodrigo
Summary Purpose: Language functional magnetic resonance imaging (fMRI) is used to noninvasively assess hemispheric language specialization as part of the presurgical work-up in temporal lobe epilepsy (TLE). White matter asymmetries on diffusion tensor imaging (DTI) may be related to language specialization as shown in controls and TLE. To refine our understanding of the effect of epilepsy on the structure,function relationships, we focused on the arcuate fasciculus (ArcF) and the inferior occipitofrontal fasciculus (IOF) and tested the relationship between DTI- and fMRI-based lateralization indices in TLE. Methods: fMRI with three language tasks and DTI were obtained in 20 patients (12 right and 8 left TLE). The ArcF, a major language-related tract, and the IOF were segmented bilaterally using probabilistic tractography to obtain fractional anisotropy (FA) lateralization indices. These were correlated with fMRI-based lateralization indices computed in the inferior frontal gyrus (Pearson's correlation coefficient). Results: fMRI indices were left-lateralized in 16 patients and bilateral or right-lateralized in four. In the ArcF, FA was higher on the left than on the right side, reaching significance in right but not in left TLE. We found a positive correlation between ArcF anisotropy and fMRI-based lateralization indices in right TLE (p < 0.009), but not in left TLE patients. No correlation was observed for the IOF. Conclusions: Right TLE patients with more left-lateralized functional activations also showed a leftward-lateralized arcuate fasciculus. The decoupling between the functional and structural indices of the ArcF underlines the complexity of the language network in left TLE patients. [source]

Hydration of exercised Standardbred racehorses assessed noninvasively using multi-frequency bioelectrical impedance analysis

Summary Reasons for performing study: In human and animal clinical practice, multi-frequency bioelectrical impedance analysis (MF-BIA) is increasingly used as a diagnostic tool to assess hydration of intra-and extracellular fluid compartments. Accurate determination of changes in hydration status within individuals over time has remained problematic due to the requirement for complete impedance-frequency relationships at the time points of interest. Objectives: To use MF-BIA in 13 Standardbred racehorses and 7 ,endurance' research horses to determine if MF-BIA could be used to track changes in total body water (TBW), intracellular fluid volume (ICFV) and extracellular fluid volume (ECFV) resulting from exercise. Methods: Jugular venous blood was sampled at rest and for 2,13 h following exercise. TBW, ECFV and plasma volume (PV) were measured at rest using indicator dilution techniques (D2O, thiocyanate and Evans Blue, respectively). TBW, ECFV, ICFV and PV were correlated to impedance measures and predictive equations used to determine hydration status from MF-BIA measures. Results: TBW loss continued throughout the recovery period, and was primarily borne by the ECF compartment at 90 min of recovery. Conclusions: MF-BIA predictions of compartmental hydration status were significantly correlated to measured/calculated decreases in these compartments. Potential relevance: Practical applications for MF-BIA in horses include monitoring of hydration status during transport and competition, assessment of body compostion, clinical health assessment and critical care management. [source]

13C-breath tests for clinical investigation of liver mitochondrial function

Ignazio Grattagliano
Eur J Clin Invest 2010; 40 (9): 843,850 Abstract Background, Mitochondria play a major role in cell energetic metabolism; therefore, mitochondrial dysfunction inevitably participates in or even determines the onset and progression of chronic liver diseases. The assessment of mitochondrial function in vivo, by providing more insight into the pathogenesis of liver diseases, would be a helpful tool to study specific hepatic functions and to develop rational diagnostic, prognostic and therapeutic strategies. Design, This review focuses on the utility of breath tests to assess mitochondrial function in humans and experimental animals. Results, The introduction in the clinical setting of specific breath tests may allow elegantly and noninvasively overcoming the difficulties caused by previous complex techniques and might provide clinically relevant information, i.e the effects of drugs on mitochondria. Substrates meeting this requirement are alpha-keto-isocaproic acid and methionine that are both decarboxylated by mitochondria. Long-and medium-chain fatty acids that are metabolized through the Krebs cycle, and benzoic acid which undergoes glycine conjugation, may also reflect the function of mitochondria. Conclusions, Breath tests to assess in vivo mitochondrial function in humans represent a potentially useful diagnostic and prognostic tool in clinical investigation. [source]

Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography,

HEPATOLOGY, Issue 6 2009
Ryota Masuzaki
Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM ,10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. Conclusions: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development. (HEPATOLOGY 2009.) [source]

Noninvasive dynamic imaging of seizures in epileptic patients

Louise Tyvaert
Abstract Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)-functional MRI (fMRI) measures noninvasively with a high-spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG-fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source]

Asynchrony of the early maturation of white matter bundles in healthy infants: Quantitative landmarks revealed noninvasively by diffusion tensor imaging

Jessica Dubois
Abstract Normal cognitive development in infants follows a well-known temporal sequence, which is assumed to be correlated with the structural maturation of underlying functional networks. Postmortem studies and, more recently, structural MR imaging studies have described qualitatively the heterogeneous spatiotemporal progression of white matter myelination. However, in vivo quantification of the maturation phases of fiber bundles is still lacking. We used noninvasive diffusion tensor MR imaging and tractography in twenty-three 1,4-month-old healthy infants to quantify the early maturation of the main cerebral fascicles. A specific maturation model, based on the respective roles of different maturational processes on the diffusion phenomena, was designed to highlight asynchronous maturation across bundles by evaluating the time-course of mean diffusivity and anisotropy changes over the considered developmental period. Using an original approach, a progression of maturation in four relative stages was determined in each tract by estimating the maturation state and speed, from the diffusion indices over the infants group compared with an adults group on one hand, and in each tract compared with the average over bundles on the other hand. Results were coherent with, and extended previous findings in 8 of 11 bundles, showing the anterior limb of the internal capsule and cingulum as the most immature, followed by the optic radiations, arcuate and inferior longitudinal fascicles, then the spinothalamic tract and fornix, and finally the corticospinal tract as the most mature bundle. Thus, this approach provides new quantitative landmarks for further noninvasive research on brain-behavior relationships during normal and abnormal development. Hum Brain Mapp, 2008. © 2007 Wiley-Liss, Inc. [source]

Imaging brain activity during natural vision using CASL perfusion fMRI

Hengyi Rao
Abstract Functional MRI (fMRI) has begun to be used to explore human brain activity during ecological and natural conditions. Arterial spin labeling (ASL) perfusion fMRI provides an appealing approach for imaging sustained brain activity during natural conditions because of its long-term temporal stability and ability to noninvasively quantify absolute cerebral blood flow (CBF). The present study used ASL perfusion fMRI to measure brain activation patterns associated with natural vision by concurrently recording CBF and blood oxygen level-dependent (BOLD) contrasts while subjects were freely viewing a cartoon movie. Reliable quantitative whole-brain CBF values (,60 mL/100g/min) as well as regional CBF values (45,80 mL/100g/min) were measured during movie viewing and resting states. The perfusion contrast revealed CBF increases in multiple visual pathway areas and frontal areas, and CBF decreases in ventromedial frontal cortex and superior temporal cortex during movie viewing compared to resting states. Concurrent BOLD contrast revealed similar but weaker activation and deactivation patterns. Regression analyses of both CBF data and BOLD data showed significant associations between activation in the middle temporal (MT) region and subjects' perception of motion. Region of interest analysis based on a priori literature-defined MT demonstrated significant monotonic stepwise associations between the intensity of motion perception and the CBF and BOLD signal changes. These results demonstrate the feasibility of using ASL perfusion fMRI for imaging both sustained and dynamic effects in neural activation during natural and ecologically valid situations, and support the notion of maintained functional segregation and specialization during natural vision. Hum Brain Mapp, 2006. © 2006 Wiley-Liss, Inc. [source]

The Use of Impedance Cardiography in Predicting Mortality in Emergency Department Patients With Severe Sepsis and Septic Shock

Anthony M. Napoli MD
Abstract Objectives:, Pulmonary artery catheterization poses significant risks and requires specialized training. Technological advances allow for more readily available, noninvasive clinical measurements of hemodynamics. Few studies exist that assess the efficacy of noninvasive hemodynamic monitoring in sepsis patients. The authors hypothesized that cardiac index, as measured noninvasively by impedance cardiography (ICG) in emergency department (ED) patients undergoing early goal-directed therapy (EGDT) for sepsis, would be associated with in-hospital mortality. Methods:, This was a prospective observational cohort study of patients age over 18 years meeting criteria for EGDT (lactate > 4 or systolic blood pressure < 90 after 2 L of normal saline). Initial measurements of cardiac index were obtained by ICG. Patients were followed throughout their hospital course until discharge or in-hospital death. Cardiac index measures in survivors and nonsurvivors are presented as means and 95% confidence intervals (CI). Diagnostic performance of ICG in predicting mortality was tested by receiver operating characteristic (ROC) curve and areas under the ROC curves (AUC) were compared using Wilcoxon test. Results:, Fifty-six patients were enrolled; one was excluded due to an inability to complete data acquisition. The mean cardiac index in nonsurvivors (2.3 L/min·m2, 95% CI = 1.6 to 3.0) was less than that for survivors (3.2, 95% CI = 2.9 to 3.5) with mean difference of 0.9 (95% CI = 0.12 to 1.71). The AUC for ICG in predicting mortality was 0.71 (95% CI = 0.58 to 0.88; p = 0.004). A cardiac index of < 2 L/min·m2 had a sensitivity of 43% (95% CI = 18% to 71%), specificity of 93% (95% CI = 80% to 95%), positive likelihood ratio of 5.9, and negative likelihood ratio of 0.6 for predicting in-hospital mortality. Conclusions:, Early, noninvasive measurement of the cardiac index in critically ill severe sepsis and septic shock patients can be performed in the ED for those who meet criteria for EGDT. There appears to be an association between an initial lower cardiac index as measured noninvasively and in-hospital mortality. ACADEMIC EMERGENCY MEDICINE 2010; 17:452,455 © 2010 by the Society for Academic Emergency Medicine [source]

Disparity between prostate tumor interior versus peripheral vasculature in response to verteporfin-mediated vascular-targeting therapy

Bin Chen
Abstract Photodynamic therapy (PDT) is a light-based cancer treatment modality. Here we employed both in vivo and ex vivo fluorescence imaging to visualize vascular response and tumor cell survival after verteporfin-mediated PDT designed to target tumor vasculature. EGFP-MatLyLu prostate tumor cells, transduced with EGFP using lentivirus vectors, were implanted in athymic nude mice. Immediately after PDT with different doses of verteporfin, tumor-bearing animals were injected with a fluorochrome-labeled albumin. The extravasation of fluorescent albumin along with tumor EGFP fluorescence was monitored noninvasively with a whole-body fluorescence imaging system. Ex vivo fluorescence microscopy was performed on frozen sections of tumor tissues taken at different times after treatment. Both in vivo and ex vivo imaging demonstrated that vascular-targeting PDT with verteporfin significantly increased the extravasation of fluorochrome-labeled albumin in the tumor tissue, especially in the tumor periphery. Although PDT induced substantial vascular shutdown in interior blood vessels, some peripheral tumor vessels were able to maintain perfusion function up to 24 hr after treatment. As a result, viable tumor cells were typically detected in the tumor periphery in spite of extensive tumor cell death. Our results demonstrate that vascular-targeting PDT with verteporfin causes a dose- and time-dependent increase in vascular permeability and decrease in blood perfusion. However, compared to the interior blood vessels, peripheral tumor blood vessels were found less sensitive to PDT-induced vascular shutdown, which was associated with subsequent tumor recurrence in the tumor periphery. © 2008 Wiley-Liss, Inc. [source]

The role of angiogenesis, vascular maturation, regression and stroma infiltration in dormancy and growth of implanted MLS ovarian carcinoma spheroids

Assaf Gilead
Abstract MLS ovarian epithelial carcinoma multicellular spheroids xenografted subcutaneously in CD-1 nude mice displayed growth delay, or dormancy, of up to 52 days. In the study reported here, implanted MLS spheroids were used for testing the role of angiogenesis and vascular maturation in triggering the initiation of tumor progression. The kinetics and impact of neovascular maturation and functionality, in dormancy, and growth of MLS spheroid xenografts were studied noninvasively by BOLD contrast MRI. MR data were supported by histologic staining for biotinylated albumin as a blood pool marker and alpha-smooth muscle actin (alpha-SMA) as marker for perivascular mural cells. Although the tumor periphery showed higher levels of total and mature vasculature than normal skin, the fraction of mature out of the total vessels as detected by MRI vascular maturation index (VMIMRI) was significantly lower in the tumor both before and after tumor exit from dormancy. The neovasculature induced by the implanted spheroid was unstable and showed cycles of vessel growth and regression. Surprisingly, this instability was not restricted to the immature vessels, but rather included also regression of mature vessels. During dormancy, neovasculature was predominantly peripheral with no infiltration into the implanted spheroid. Infiltration of alpha-SMA positive stroma cells into the spheroid was associated with functional vascularization and tumor growth. Thus, stroma infiltration and vascular maturation are an important checkpoint linking the angiogenic switch with initiation of tumor progression. © 2003 Wiley-Liss, Inc. [source]

Patterns of Presentation, Diagnosis, and Treatment in Older Patients with Colon Cancer and Comorbid Dementia

Supriya K. Gupta MD
Objectives: To estimate patterns of colon cancer presentation, diagnosis, and treatment according to history of dementia using National Cancer Institute (NCI) Surveillance, Epidemiology, and End-Result (SEER) Medicare data. Design: Population-level cohort study. Setting: NCI's SEER-Medicare database. Participants: A total of 17,507 individuals aged 67 and older with invasive colon cancer (Stage I-IV) were identified from the 1993,1996 SEER file. Medicare files were evaluated to determine which patients had an antecedent diagnosis of dementia. Measurements: Parameters relating to the cohort's patterns of presentation and care were estimated using logistic regressions. Results: The prevalence of dementia in the cohort of newly diagnosed colon cancer patients was 6.8% (1,184/17,507). Adjusting for possible confounders, dementia patients were twice as likely to have colon cancer reported after death (i.e., autopsy or death certificate) (adjusted odds ratio (AOR)=2.31, 95% confidence interval (CI)=1.79,3.00). Of those diagnosed before death (n=17,049), dementia patients were twice as likely to be diagnosed noninvasively than with tissue evaluation (i.e., positive histology) (AOR=2.02 95% CI=1.63,2.51). Of patients with Stage I -III disease (n=12,728), patients with dementia were half as likely to receive surgical resection (AOR=0.48, 95% CI=0.33,0.70). Furthermore, of those with resected Stage III colon cancer (n=3,386), dementia patients were 78% less likely to receive adjuvant 5-fluorouracil (AOR=0.22, 95% CI=0.13,0.36). Conclusion: Although the incidences of dementia and cancer rise with age, little is known about the effect of dementia on cancer presentation and treatment. Elderly colon cancer patients are less likely to receive invasive diagnostic methods or curative-intent therapies. The utility of anticancer therapies in patients with dementia merits further study. [source]

Monitoring of glucose permeability in monkey skin in vivo using Optical Coherence Tomography

Mohamad G. Ghosn
Abstract Topical trans-dermal delivery of drugs has proven to be a promising route for treatment of many dermatological diseases. The aim of this study is to monitor and quantify the permeability rate of glucose solutions in rhesus monkey skin noninvasively in vivo as a primate model for drug diffusion. A time-domain Optical Coherence Tomography (OCT) system was used to image the diffusion of glucose in the skin of anesthetized monkeys for which the permeability rate was calculated. From 5 experiments on 4 different monkeys, the permeability for glucose-20% was found to be (4.41 ± 0.28) 10,6 cm/sec. The results suggest that OCT might be utilized for the noninvasive study of molecular diffusion in the multilayered biological tissues in vivo. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

Effect of Postconditioning on Coronary Blood Flow Velocity and Endothelial Function and LV Recovery After Myocardial Infarction

Objective: Postconditioning is a novel approach to myocardial protection during ischemia reperfusion. Our study observed the effect of postconditioning on coronary blood flow velocity and endothelial function in patients who underwent emergency percutaneous coronary intervention (PCI). Methods: Ninety-four patients with their first acute myocardial infarction who underwent revascularization within 12 hours of onset by primary PCI were recruited in the study. All the patients were randomized to two groups, IR group (PCI without postconditioning) and Postcond group (PCI with postconditioning). Corrected TIMI frame count (CTFC) was used to evaluate velocity of coronary blood after PCI. Creatine phosphokinase (CK), CK-MB, and malondialdehyde (MDA) were measured before and after PCI. Arterial endothelial function was studied noninvasively by examination of brachial artery responses to endothelium-dependent and endothelium-independent stimuli by echo Doppler technique. Wall motion score index (WMSI) was assessed by two-dimensional echocardiography before and 8 weeks after angioplasty. Results: There were no significant differences between the two groups with regard to age, sex, presence of angiographically visible collaterals, and elapsed time from the onset of symptoms until perfusion. Patients with postconditioning had much faster CTFC than patients without postconditioning (25.38 ± 5.35 vs 29.23 ± 5.54). After 8 weeks, the WMSI improved significantly in both groups, but the ,WMSI in Postcond group was significantly larger than that of IR group (1.20 ± 0.30 vs 1.04 ± 0.36, P < 0.05). There was a significant negative correlation between ,WMSI and CTFC in IR group and Postcond group (r =,0.9032, P < 0.01; r =,0.7884, P < 0.01). The peaks of CK and CK-MB of Postcond group were much lower than that of IR group (1236.57 ± 813.21 U/L vs 1697.36 ± 965.74 U/L; 116.92 ± 75.83 U/L vs 172.41 ± 92.64 U/L), and MDA-reactive products were significantly lower than that in the IR group at any same time after PCI. All patients with acute myocardial infarction had a depressed endothelium-dependent vasodilation function, while the endothelium-dependent vasodilation function was improved in Postcond group. Conclusion: Postconditioning is a simple, operative procedure for salvaging the coronary endothelial function and cardiomyocyte. It could be used widely in clinic and to better the prognosis of acute myocardial infarction. [source]

Conscious Sedation with Intermittent Midazolam and Fentanyl in Electrophysiology Procedures

Objectives: To determine the safety and efficacy of intermittent midazolam and fentanyl conscious sedation for electrophysiology procedures (EP). Background: Intermittent midazolam and fentanyl conscious sedation was administered in 700 consecutive cases (175 radiofrequency ablations, 163 EP studies, 261 pacemakers, and 101 implantable cardioverter-defibrillators) for 471 patients (239 males, 51%) mean age 65 ± 15 years. The mean dose of midazolam was 0.063 mg/kg/hr and fentanyl was 0.591,g/kg/hr. Methods: Cardiac rate and rhythm were monitored continuously, while blood pressure and arterial oxygen saturation were noninvasively assessed evevy 5 minutes. Drugs were administered in aliquots of 0.5 to 2.0 mg of midazolam and 6.25 to 25 ,g of fentanyl as determined by clinical condition every 15 to 30 minutes. Results: There were no deaths. In no case was endotracheal intubation required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning (12 cases, 1.7%), increased F1O2 (3 cases, 0.4%), or intravenous naloxone (2 cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mmHg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (4 cases, 0.6%). No patient stay was prolonged due to sedation. Only five patients (0.7%) had any recollection of the procedure, while two (0.3%) were aware of pain. All hypoxemic episodes occurred during the first hour, whereas 43% (6/14) of hypotensive episodes occurred after the first hour. Conclusion: Conscious sedation with intermittent midazolam and fentanyl is safe and eficacious for a broad range of EP procedures. (J Interven Cardiol 2001; 14:143,146) [source]

Imaging biomarkers of cardiovascular disease

Jinnan Wang PhD
Abstract Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Current clinical techniques that rely on stenosis measurement alone appear to be insufficient for risk prediction in atherosclerosis patients. Many novel imaging methods have been developed to study atherosclerosis progression and to identify new features that can predict future clinical risk. MRI of atherosclerotic vessel walls is one such method. It has the ability to noninvasively evaluate multiple biomarkers of the disease such as luminal stenosis, plaque burden, tissue composition and plaque activity. In addition, the accuracy of in vivo MRI has been validated against histology with high reproducibility, thus paving the way for application to epidemiological studies of disease pathogenesis and, by serial MRI, in monitoring the efficacy of therapeutic intervention. In this review, we describe the various MR techniques used to evaluate aspects of plaque progression, discuss imaging-based measurements (imaging biomarkers), and also detail their validation. The application of plaque MRI in clinical trials as well as emerging imaging techniques used to evaluate plaque compositional features and biological activities are also discussed. J. Magn. Reson. Imaging 2010;32:502,515. © 2010 Wiley-Liss, Inc. [source]

Noninvasive in vivo electron paramagnetic resonance study to estimate pulmonary reducing ability in mice exposed to NiO or C60 nanoparticles

Hidekatsu Yokoyama MD
Abstract Purpose To develop new methods that can estimate the influences of manufactured nanomaterials on biological systems, the in vivo pulmonary reducing ability of mice that had received inhalation exposures to NiO or C60 nanoparticles was investigated using a 700 MHz electron paramagnetic resonance (EPR) spectrometer. Materials and Methods NiO or C60 suspensions were atomized and mice in exposure chambers inhaled the resulting aerosol particles for 3 hours. The exposure conditions, number-based geometric average diameters, and the average number concentration were precisely controlled at almost the same levels for both NiO and C60 nanoparticles. Two days or 2 weeks after exposure, an EPR study was conducted noninvasively. Temporal changes in EPR signal intensity at the target area (ie, lung field) were obtained by the region-selected intensity determination (RSID) method. Results NiO nanoparticles significantly suppressed pulmonary reducing ability 2 days and 2 weeks after exposure, but C60 nanoparticles had no such effect. Conclusion This is the first in vivo estimation of the reducing ability in experimental animals exposed to manufactured nanoparticles. J. Magn. Reson. Imaging 2009. © 2009 Wiley-Liss, Inc. [source]

Fast and optimized T1 mapping technique for the noninvasive quantification of gastric secretion

Reto Treier MSc
Abstract Purpose To evaluate the noninvasive quantification of gastric secretion volume after administration of a labeled viscous glucose solution by fast T1 mapping. Materials and Methods T1 values of a series of labeled and diluted glucose solutions were measured in vitro to characterize the interrelationship between T1 and contrast agent concentration (CGd) as well as the dependency of relaxivity and reference T1 (T10) on the macromolecular concentration. Abdominal T1 mapping in five healthy volunteers of different body mass index was performed after filling an intragastric balloon with a labeled and diluted glucose solution. In additional ex vivo experiments, T1 values of gastric (GJ) and duodenal juice (DJ) and 0.1 N HCl solution were determined. Results A linear relationship between relaxivity and macromolecular concentration and between T10 and macromolecular concentration was found. The in vitro T1,CGd calibration curve was successfully validated in all volunteers. T1 values of GJ, DJ, and HCl (2939 msec vs. 2858 msec vs. 2760 msec) were close to the T1 of water (,3000 msec). Conclusion The presented method allows one to noninvasively quantify the spatial distribution of gastric secretory products in the human stomach and provides a valuable tool for evaluating the efficacy of drugs to stimulate/inhibit gastric secretion. J. Magn. Reson. Imaging 2008;28:96,102. © 2008 Wiley-Liss, Inc. [source]

Current status and future potential of MRI-guided focused ultrasound surgery

Ferenc A. Jolesz MD
Abstract The combination of the imaging abilities of magnetic resonance imaging (MRI) with the ability to delivery energy to targets deep in the body noninvasively with focused ultrasound presents a disruptive technology with the potential to significantly affect healthcare. MRI offers precise targeting, visualization, and quantification of temperature changes and the ability to immediately evaluate the treatment. By exploiting different mechanisms, focused ultrasound offers a range of therapies, ranging from thermal ablation to targeted drug delivery. This article reviews recent preclinical and tests clinical of this technology. J. Magn. Reson. Imaging 2008;27:391,399. © 2008 Wiley-Liss, Inc. [source]

In vivo bioluminescence imaging study to monitor ectopic bone formation by luciferase gene marked mesenchymal stem cells

Cristina Olivo
Abstract Mesenchymal stem cells (MSCs) represent a powerful tool for applications in regenerative medicine. In this study, we used in vivo bioluminescence imaging to noninvasively investigate the fate and the contribution to bone formation of adult MSCs in tissue engineered constructs. Goat MSCs expressing GFP-luciferase were seeded on ceramic scaffolds and implanted subcutaneously in immune-deficient mice. The constructs were monitored weekly with bioluminescence imaging and were retrieved after 7 weeks to quantify bone formation by histomorphometry. With increasing amounts of seeded MSCs (from 0 to 1,×,106 MSC/scaffold), a cell-dose related increase in bioluminescence was observed at all time points, correlating with increased bone formation at 7 weeks. To investigate the relevance of MSC proliferation to bone deposition, cell-seeded scaffolds were irradiated. The irradiated cells were functional with respect to oxygen consumption but no increase in bioluminescence was observed in vivo, and only minimal bone was produced. Proliferating MSCs are likely required for initiation of bone formation in tissue engineered constructs in vivo. Bioluminescence is a useful tool to monitor cellular responses and predict bone formation in vivo. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:901,909, 2008 [source]