Local Vascular Effects Research Articles

Comparison of effects of peripheral vasculature on tonometric radial pulse and cuff-based brachial pulse waveform as used in estimation of central aortic pressures.

Aortic pressure estimation requires reliable peripheral pulse waveform acquisition. The peripheral waveform can change with local vascular effects that can be independent of aortic pressure. This study quantifies the effects of peripheral vasculature changes on radial and brachial waveforms. In 20 subjects (37± 15 years, 7 female), brachial volumetric displacement (cuff-based) and radial tonometry waveforms were simultaneously measured whilst a cuff around the hand on the same arm was inflated to induce transmural pressures of -60, -30, -15, 0, 15 and 30 mmHg, altering local peripheral resistance and compliance by graded arterial wall unloading. Aortic blood pressure (BP), augmentation index (AIx) and ejection duration were calculated from the measurements using a generalized transfer function. The parameters under unloaded conditions were compared to baseline measurements. Brachial systolic and diastolic BP did not change throughout the experiment. Altering peripheral resistance and compliance did not significantly change calculated aortic BP values, although changes were nominally greater for radial (maximum +8±1 mmHg) compared to brachial (maximum +2±1 mmHg) waveforms. AIx at 0 mmHg transmural pressure (maximum arterial wall unloading) was higher when derived from radial waveforms (+24±3%, p<0.001) but not when derived from brachial waveforms. Localized changes in peripheral resistance and compliance affect tonometer acquired radial waveforms but not volumetric displacement acquired brachial pressure waveforms, as judged by computed central aortic augmentation pressure parameters. This suggests aortic pressure estimation from the brachial cuff waveform is less sensitive to peripheral vasculature disturbances that alter the peripheral arterial pulse morphology.

Irisin-A Pancreatic Islet Hormone.

Irisin is a myokine involved in glucose homeostasis. It is primarily expressed in skeletal muscle, but also in the pancreas. This study aimed to elucidate its presence and role in the islets of Langerhans—i.e., its effect on insulin and glucagon secretion as well as on blood flow in the pancreas. The precursor of irisin, fibronectin type III domain-containing protein 5 (FNDC5), was identified in rat and human islets by both qPCR and immunohistochemistry. Both α- and β-cells stained positive for FNDC5. In human islets, we found that irisin was secreted in a glucose-dependent manner. Neither irisin nor an irisin-neutralizing antibody affected insulin or glucagon secretion from human or rat islets in vitro. The insulin and glucagon content in islets was not altered by irisin. The intravenous infusion of irisin in Sprague Dawley rats resulted in nearly 50% reduction in islet blood flow compared to the control. We conclude that irisin is an islet hormone that has a novel role in pancreatic islet physiology, exerting local vascular effects by diminishing islet blood flow without affecting insulin secretion per se.

Effects of vehicle microdialysis solutions on cutaneous vascular responses to local heating.

Microdialysis is a minimally invasive technique often paired with laser Doppler flowmetry to examine cutaneous microvascular function, yet presents with several challenges, including incompatibility with perfusion of highly lipophilic compounds. The present study addresses this methodological concern, with an emphasis on the independent effects of commonly used vehicle dialysis solutions to improve solubility of pharmacological agents with otherwise low aqueous solubility. Four microdialysis fibers were placed in the ventral forearm of eight subjects (4 men, 4 women; 25 ± 1 yr) with sites randomized to serve as 1) control (lactated Ringer's), 2) Sodium carbonate-bicarbonate buffer administered at physiological pH [SCB-HCl; pH 7.4, achieved via addition of hydrochloric acid (HCl)], 3) 0.02% ethanol, and 4) 2% dimethyl sulfoxide (DMSO). After baseline (34°C), vehicle solutions were administered throughout a standardized local heating protocol to 42°C. Laser Doppler flowmetry provided an index of blood flow. Cutaneous vascular conductance was calculated and normalized to maximum (%CVCmax, sodium nitroprusside and 43°C local heat). The SCB-HCl solution increased baseline %CVCmax (control: 9.7 ± 0.8; SCB-HCl: 21.5 ± 3.5%CVCmax; P = 0.03), but no effects were observed during heating or maximal vasodilation. There were no differences with perfusion of ethanol or DMSO at any stage of the protocol ( P > 0.05). These data demonstrate the potential confounding effects of some vehicle dialysis solutions on cutaneous vascular function. Notably, this study provides evidence that 2% DMSO and 0.02% ethanol are acceptable vehicles with no confounding local vascular effects to a standardized local heating protocol at the concentrations presented. NEW & NOTEWORTHY This study examined the independent effects of common vehicle solutions on cutaneous vascular responses. A basic buffer (SCB-HCl) caused baseline vasodilation; 2% DMSO and 0.02% ethanol had no effects. This highlights the need for considering potential confounding effects of solubilizing solutions when combined with low aqueous soluble pharmacological agents. Importantly, DMSO and ethanol do not appear to influence cutaneous vascular function during baseline or local heating at the concentrations studied, allowing their use without confounding effects.

ATP‐sensitive K+ Channel Inhibition via Glibenclamide Does Not Increase Lumbar or Renal Sympathetic Nerve Discharge in Healthy Rats

ATP‐sensitive K+ (KATP) channels contribute to exercise‐induced hyperemia and O2 delivery in skeletal muscle. KATP channel inhibition via glibenclamide (GLI) increases mean arterial pressure (MAP) and reduces blood flow to the rat hindlimb during exercise: demonstrating greater reductions in oxidative compared to glycolytic muscles. Whether this control via KATP channels is mediated locally within skeletal muscle by decreased vascular hyperpolarization or alternatively by increased sympathetic nerve activity instigated within the rostral ventrolateral medulla (Guo et al. J. Pharmacol. Exp. Therapeut. 338:458–65, 2011) or other cardiovascular control centers is unknown. We hypothesized that KATP channel inhibition via intravascular infusion of GLI would increase MAP without increasing lumbar and renal sympathetic nerve discharge (SND). In 12 male anesthetized Sprague‐Dawley rats, lumbar (n=8) and renal (n=8) nerves were isolated for measurement of SND. Following 60 min stabilization after surgery, a bolus infusion of saline (CON) was administered via the femoral vein catheter and SND, MAP (n=12), and HR (n=12) were recorded for 10 min. This protocol was then used following a bolus infusion of GLI (5 mg kg−1 in ~1 mL heparinized saline). SND was calculated as percent change from baseline (ΔSND (%)). There were no significant changes in MAP, HR, or lumbar ΔSND (%) following CON (P &gt; 0.05 for all) and only minute 8 exhibited marginally increased renal ΔSND (%) (P &lt; 0.05). Compared to CON, GLI increased MAP (min 3–10), reduced lumbar ΔSND (%) (min 2–10; up to 47%), and reduced renal ΔSND (%) (min 2–9; up to 36%) (P &lt; 0.05 for all). There were no significant changes in HR due to GLI (P &gt; 0.05). These results demonstrate that KATP inhibition produces a decrease in both lumbar and renal SND likely related to increased MAP. Therefore, reductions in exercising muscle blood flow and O2 delivery following GLI do not result from enhanced sympathetic activity; supporting that vasomotor control via KATP channels is likely mediated by local vascular effects within skeletal muscle.Support or Funding InformationNIH HL‐2‐108328

Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy.

Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005–2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken.

Use Pulsating Electro Magnetic Field (PEMF) in physical Therapy.

The aim of this paper is to look into clinical applications and potential benefits. This study postulated that (PEMF) are "read" by the body as electrical stimulation producing endorphin release especially if it is a pulsed flow others cite the gate theory of differential neural transmission alterations or realignment of molecular structures, effecting in enzyme and nization products The production of heat when ions are in a (PEMF) Every tissue in the body is bathed in blood The main ingredient of blood is haemoglobin, with the "heme" representing magnetic iron. Surely there is a general effect on all tissues in achieving polar alignment (i.e. north to south) when in a (PEMF) Optimal alignment may very well be involved in the increased blood flow Regardless of how, the fact remains that it does work There are many physiologic benefits attributed to (PEMF) including-Increased oxygenation Enhanced blood flow Hormonal production. It is suggested that the body "reads" (PEMF) as an electric phenomenon (i.e. stimulation), especially if it is a pulsed flow. The most strongly supported applications relate to recovery after bone damage/fracture, pain management and to a lesser extent, wound healing. It may transpire that this therapy is useful for local vascular and microcirculatory effects and for soft tissue problems (after injury) and facilitated repair in musculoskeletal lesions, pain management and oedema resolution. One would certainly not want to restrict the clinical applications to these fields, just that they are the strongest evidenced to date.

The effect of intermittent pneumatic compression of legs on the levels of nitric oxide related species in blood and on arterial function in the arm

BackgroundIntermittent pneumatic compression (IPC) of legs exerts beneficial local vascular effects, possibly through local release of nitric oxide (NO). However, studies demonstrating systemic transport of nitrogen oxide species and release of NO prompt the question of whether IPC could also exert nonlocal effects. We tested whether IPC (1) affects systemic levels of nitrite, S-nitrosothiols and red blood cell (RBC) NO, and (2) exerts vasoactive effects in the brachial artery (BA), although this hypothesis-generating pilot study did not investigate cause and effect relationship between (1) and (2). MethodsIn 10 healthy subjects, ages 24–39years, we measured plasma nitrite, plasma S-nitrosothiols and RBC-NO from venous blood samples drawn before and after IPC treatment. We also measured BA responses to 5min of upper arm occlusion at rest and during1h of leg IPC. ResultsThere was a significant decrease in plasma nitrite (112±26nM to 90±15nM, p=0.0008) and RBC-NO (129±72nM to 102±41nM, p=0.02). Plasma S-nitrosothiols were unchanged (5.79±4.81nM to 6.27±5.79nM, p=0.3). BA occlusion-mediated constriction (OMC) was significantly attenuated with IPC treatment (−43±13% to −33±12%, p=0.003). High-flow mediated BA dilation was unchanged (13.3±9.4% to 11.5±7.2%, p=0.2). ConclusionPlasma nitrite, RBC-NO, and BA OMC decreased with leg IPC. We hypothesize that this decrease in circulatory pool of plasma nitrite and RBC-NO may result from the transfer of their NO-bioactivity from blood to the hypoxic arm tissue, to be stored and released under hypoxic stress and oppose OMC. Future studies should investigate whether IPC-induced decreases in brachial OMC are caused by the changes in systemic NO activity, and whether leg IPC could benefit distant arterial function in systemic cardiovascular disease.

The effect of fluence rate on the acute response of vessel diameter and red blood cell velocity during topical 5-aminolevulinic acid photodynamic therapy

In a previous study it is shown that for topically applied ALA-PDT, PpIX concentration correlates with vascular changes including vasoconstriction and/or vascular leakage of small vessels and arterioles in the mouse epidermis and dermis. In this study we report on vascular responses induced by ALA-PDT for different fluence rates, including both changes in vessel diameter and dynamics in RBC velocity in arterioles, imaged using intra-vital confocal microscopy in skinfold chambers in hairless mice. Our interest is in the dynamics of vascular changes in the early stages of illumination. We have determined the total PDT dose to be relatively low, 13 J cm(-2), and fluence rates of 26, 65 and 130 mW cm(-2) were investigated. Local vascular effects occurred very soon after the start of the therapeutic illumination in ALA-PDT. In this study, we did not find a significant difference between fluence rates. Arterioles were particularly sensitive to vasoconstriction during low dose PDT, often resulting in complete vasoconstriction. When we observed complete vasoconstriction, this coincided with changes in RBC velocity. Since the therapeutic effects of PDT are dependent on a fine balance between the need for oxygen during illumination and disruption of the vasculature, the results of the present study add to our understanding of acute vascular effects during ALA-PDT and aid our efforts to optimize PDT using porphyrin pre-cursors.

Function of the sympathetic supply in acute and chronic experimental joint inflammation

Joints are densely innervated by postganglionic sympathetic nerve fibers. These fibers control the blood flow in the joint and vascular permeability, either directly or indirectly, in cooperation with leukocytes. Chemical sympathectomy or suppression of adrenergic signaling significantly reduces inflammatory processes in the initial acute state of inflammation whereas the same procedures may increase inflammation at later stages. These findings indicate that the sympathetic nervous system supports the development of inflammation but may reduce inflammation at more chronic stages. During chronic inflammation the density of sympathetic nerve fibers in synovial tissue is reduced but other tyrosine hydroxylase-positive cells secreting noradrenaline appear in the inflamed joint. In addition to local vascular effects in the joint, the sympathetic nervous system influences numerous immune processes in the joint and in lymphoid organs. Hence the net effect of the sympathetic nervous system on inflamed tissue results from local sympathetic effects in the joint as well as from sympathetic influences on major systemic immune processes.

Levobupivacaine vs. bupivacaine for third molar surgery: quality of anaesthesia, postoperative analgesia and local vascular effects

The main purpose of this prospective, double-blind, randomized study was to evaluate anaesthetic parameters, postoperative analgesia and vasoactive properties of levobupivacaine and bupivacaine for lower third molar surgery. Sixty patients (ASA I) were scheduled for lower third molar surgery under inferior alveolar nerve block, lingual nerve block and buccal nerve block (mandibular nerve blocks) obtained with 3 ml of 0.5 % levobupivacaine and 3 ml of 0.5 % bupivacaine. Success rate, onset and duration of three nerve bocks were evaluated by electrical pulp testing, pinprick testing and signs of soft tissue anaesthesia (patient-reported numbness). Intensity of intraoperative anaesthesia and postoperative analgesia were measured with visual analogue scale (VAS) and numeric rating scale (NRS). The time of first postoperative pain reported and analgesic consumption were also recorded. The laser Doppler flowmetry was used for the measurement of the first premolar pulpal blood flow. There were no differences between levobupivacaine and bupivacaine regarding the success rate, onset and duration of mandibular nerve blocks as well as intensity of postoperative analgesia and analgesic consumption. Intensity of intraoperative anaesthesia and duration of postoperative analgesia were significantly higher in the levobupivacaine than in the bupivacaine group. Both anaesthetics showed similar biphasic vasoactive effect. Levobupivacaine 0.5 % achieved superiority over bupivacaine 0.5 % in the intensity of intraoperative anaesthesia and duration of postoperative analgesia for lower third molar surgery under the mandibular nerve blocks. It seems that the plain levobupivacaine (0.5 %) could be an effective alternative to plain bupivacaine (0.5 %) in those dental procedures which require profound bone and soft tissue anaesthesia.

Abstract 141: The Loss of Nrf2 Enhances Vascular Inflammation but Reduces Atherosclerosis via Effects on Plasma Lipids in LDL Receptor Deficient Mice Fed High Fat Diet

OBJECTIVE Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant and detoxifying enzymes affording cytoprotection in the cardiovascular system. We have previously reported that Nrf2 deficiency specific to bone marrow derived cells aggravates atherosclerosis in LDL receptor deficient (LDLR-/-) mice. Furthermore, Nrf2 deficiency in macrophages enhances foam cell formation and promotes the proinflammatory phenotype. In contrast, the total loss of Nrf2 has been shown to protect against atherogenesis in apoE-deficient mice. The mechanism by which Nrf2 deficiency affords atheroprotection in apoE-model is currently unknown, but combined systemic and local vascular effects have been proposed. Given these contrasting results, we aimed at assessing the effect of total loss of Nrf2 on atherogenesis in hypercholesterolemic LDLR-/- mice. METHODS AND RESULTS Nrf2-/- mice were cross-bred to LDLR-/- mice and fed a high fat diet (HFD) for 6 or 12 weeks. The degree of atherosclerosis was assessed from the cross-sections of proximal aorta. Nrf2 deficiency decreased atherosclerosis in females from 17.2±8.7 % (mean ±SD, n=11-25) to 12.3±4.6 % (p=0.1) and in males from 11.2±3.9 % to 7.6±4.6 % (p=0.025) after 6 weeks on HFD. After 12 weeks on HFD the effects were more pronounced, as Nrf2 deficiency decreased atherosclerosis from 36.5±5.5 % to 30.3±3.5 % in females (p=0.001) and from 30.6±5.7 % to 21.3±6.9 % in males (p=0.005). Nrf2 deficiency also increased the macrophage content relative to lesion area. Supporting systemic effects, Nrf2 deficiency reduced plasma total cholesterol from 24.0±8.4 mmol/l to 10.6±6,7 mmol/l (p=0.006) and triglyceride levels from 3.6±1.4 mmol/l to 1.7±1.2 mmol/l (p=0.008) in males after 6 weeks on HFD. CONCLUSIONS In contrast to bone marrow specific Nrf2 deficiency, total loss of Nrf2 aggravates atherosclerosis in LDLR-/- mice likely via systemic effects on lipid metabolism.

The absence of macrophage Nrf2 promotes early atherogenesis

The loss of nuclear factor E2-related factor 2 (Nrf2) has been shown to protect against atherogenesis in apoE-deficient mice. The mechanism by which Nrf2 deficiency affords atheroprotection in this model is currently unknown, but combined systemic and local vascular effects on lesion macrophages have been proposed. We investigated the effect of bone marrow-specific loss of Nrf2 on early atherogenesis in low-density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice, and assessed the effect of Nrf2 on cellular accumulation of modified LDLs and the expression of inflammatory markers in macrophages. The effect of bone marrow-specific loss of Nrf2 on atherogenesis was studied using bone marrow transplantation of wild-type (WT) or Nrf2(-/-) bone marrow to LDLR(-/-) mice. Mice transplanted with Nrf2(-/-) bone marrow and fed a high-fat diet for 6 weeks exhibited significantly larger atherosclerotic lesions than WT bone marrow transplanted mice. Moreover, in thioglycollate-elicited Nrf2(-/-) macrophages, the uptake of acetylated and malondialdehyde-modified LDLs was increased in comparison with WT controls, with the concomitant increase in the expression of scavenger receptor A and toll-like receptor 4. In addition, the expression of pro-inflammatory monocyte chemoattractant protein-1 and interleukin-6 were increased in Nrf2(-/-) vs. WT macrophages. Nrf2 deficiency specific to bone marrow-derived cells aggravates atherosclerosis in LDLR(-/-) mice. Furthermore, the loss of Nrf2 in macrophages enhances foam cell formation and promotes the pro-inflammatory phenotype.

Characterization of Local Vascular Effects of the Nitric Oxide Inhibitor NG‐Monomethyl‐L‐Arginine on Dorsal Hand Veins

Infusion of NG-monomethyl-L-arginine (L-NMMA; 6.4 µmol/min) into hand veins can cause a 20% increase in vein size in specific subjects. This study explored potential underlying mechanisms in healthy male participants. Ten healthy male participants received in phenylephrine (PE)-preconstricted veins a dose-response curve (DRC) to L-NMMA (0.2-6.4 µmol/min) without and with coinfusion of the endothelium-dependent dilator histamine, a DRC to L-arginine with and without coinfusion of L-NMMA, a DRC to NG-monomethyl-D-arginine (D-NMMA), and a DRC to L-NMMA in prostaglandin F(2α)-(PGF(2α))-preconstricted veins. Participants were classified as L-NMMA responders (R) and nonresponders (NR). Infusion of L-NMMA resulted in a maximum venodilation of 38% ± 11% (R) versus 10% ± 5% (NR; P = .005). In PGF(2α)-preconstricted veins, L-NMMA caused venodilation to 26% ± 34% (NS) in responders. Results suggest that endothelial nitric oxide synthase-mediated formation of nitric oxide (NO) from L-NMMA in doses >3.2 µmol/min and continuous PE-induced α-adrenergic stimulation resulting in release of very small amounts of NO from L-NMMA contribute to the observed L-NMMA-induced increase in vein size. Venous reactivity to L-NMMA resulting in a phenotype as R or NR is most likely genetically predetermined, which requires further study.

Combination of photodynamic therapy and immunomodulation for skin diseases—update of clinical aspects

In dermatology, photodynamic therapy (PDT) has become a well established treatment modality which has been shown to be effective and safe for many skin and mucosal disorders. Pre-clinical and clinical studies demonstrate that, in addition to the direct local cytotoxicity and vascular effects, PDT can induce various host immune responses. Recent clinical data also show that improved clinical outcomes can be obtained through the sequential use of PDT and immunomodulation. This article will provide an update on the current status of such a combination in dermatological applications.

NF-E2–Related Factor 2 Promotes Atherosclerosis by Effects on Plasma Lipoproteins and Cholesterol Transport That Overshadow Antioxidant Protection

To test the hypothesis that NF-E2-related factor 2 (Nrf2) expression plays an antiatherogenic role by its vascular antioxidant and anti-inflammatory properties. Nrf2 is an important transcription factor that regulates the expression of phase 2 detoxifying enzymes and antioxidant genes. Its expression in vascular cells appears to be an important factor in the protection against vascular oxidative stress and inflammation. We developed Nrf2 heterozygous (HET) and homozygous knockout (KO) mice on an apolipoprotein (apo) E-null background by sequential breeding, resulting in Nrf2(-/-), apoE(-/-) (KO), Nrf2(-/+), apoE(-/-) (HET) and Nrf2(+/+), and apoE(-/-) wild-type littermates. KO mice exhibited decreased levels of antioxidant genes with evidence of increased reactive oxygen species generation compared with wild-type controls. Surprisingly, KO males exhibited 47% and 53% reductions in the degree of aortic atherosclerosis compared with HET or wild-type littermates, respectively. Decreased atherosclerosis in KO mice correlated with lower plasma total cholesterol in a sex-dependent manner. KO mice also had a decreased hepatic cholesterol content and a lower expression of lipogenic genes, suggesting that hepatic lipogenesis could be reduced. In addition, KO mice exhibited atherosclerotic plaques characterized by a lesser macrophage component and decreased foam cell formation in an in vitro lipid-loading assay. This was associated with a lower rate of cholesterol influx, mediated in part by decreased expression of the scavenger receptor CD36. Nrf2 expression unexpectedly promotes atherosclerotic lesion formation in a sex-dependent manner, most likely by a combination of systemic metabolic and local vascular effects.

Recent achievements in the management of Raynaud&amp;rsquo;s phenomenon

Raynaud's phenomenon is a clinical disorder with episodic digital ischemic vasospasm triggered by cold- or emotional-stress. It was first mentioned by Maurice Raynaud in 1862 describing "a local asphyxia of the extremities" and was further divided into primary Raynaud's disease and secondary Raynaud's phenomenon, which is often related to connective tissue diseases, but also physical or chemical strain. Though pathophysiology of Raynaud's phenomenon is still poorly understood, systemic and local vascular effects are most likely to be involved in primary Raynaud's disease. In secondary Raynaud's phenomenon additional abnormalities in vascular structure and function may play the major role. Thus, medical treatment of Raynaud's phenomenon remains unsatisfactory, due to limited understanding of pathophysiological mechanisms. This review addresses current evidence for medical treatment of primary and secondary Raynaud's phenomenon with regard to pathophysiological mechanisms as well as future perspectives.

HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain.

Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data.

Combination of photodynamic therapy and immunomodulation: Current status and future trends

Photodynamic therapy (PDT) has been used for the treatment of nonmalignant and malignant diseases from head to toe. Over the last decade its clinical application has gained increasing acceptance around the world. Pre-clinical studies demonstrate that, in addition to the direct local cytotoxicity and vascular effects, PDT can induce various host immune responses. Recent clinical data also show that improved clinical outcomes are obtained through the combination of PDT and immunomodulation. This review will summarize and discuss recent progress in developing innovative regimen of PDT combined with immunomodulation for the treatment of both nonmalignant and malignant diseases.

Ropivacaine versus Lidocaine in Digital Nerve Blocks: A Prospective Study

Ropivacaine is a relatively new long-acting amide local anesthetic. Since its introduction in 1996, it has been used for subcutaneous infiltration; epidural, intrathecal, and peripheral nerve block surgery; and postoperative analgesia. However, it has never been used for digital blocks. This prospective, randomized, double-blind study compares the digital block results following the administration of 2.5 ml of 0.75% ropivacaine solution and 2.5 ml of 2% lidocaine solution. From March of 1999 to March of 2001, 70 adult patients who underwent immediate reconstruction for traumatic injuries of the digits were prospectively randomized into two groups. Group A (n = 35) received 2.5 ml 0.75% ropivacaine and group B (n = 35) received 2.5 ml of 2% lidocaine for digital anesthesia. Onset time of anesthetic action, duration of anesthesia, time until first postoperative requirement for pain medication, and digital-brachial artery systolic blood pressure index were recorded and evaluated. Local vascular effects were observed visually. No side effects were observed. Lidocaine had the quickest onset of anesthesia, with a mean time of 1.3 minutes (range, 1 to 2.7 minutes). Ropivacaine had a mean onset time of 4.5 minutes (range, 3.5 to 5.5 minutes). The mean duration of postoperative anesthesia for lidocaine was 2.4 hours (range, 1.4 to 4 hours), compared with 21.5 hours for ropivacaine and less requirement for analgesics during the first 24 postoperative hours (p < 0.05) (range, 19 to 23 hours). No significant difference was found between the digital-brachial artery systolic blood pressure index of group A compared with group B. Ropivacaine can be used effectively as a local anesthetic for digital nerve blocks. It can be used for prolonged operations (>1.5 hours) without additional injections and can provide long-lasting postoperative analgesia.

Acute and mid-term local vascular effects of compliant balloon inflation (GuardWire system) on saphenous vein bypass grafts: An angiographic analysis

Background The GuardWire distal protection device reduces the incidence of periprocedural complications during percutaneous stenting of diseased saphenous vein grafts. Its mechanism of action is based on the occlusion of the vessel distal to the lesion with an inflated compliant balloon before the intervention, and the aspiration of embolized material after stent implantation. Although no safety issues related to the compliant balloon have been reported in vein graft treatment, concerns related to the potential injury of the balloon on the vessel wall have been raised. We thus evaluated the angiographic outcome of the vein graft segment where the compliant balloon of the GuardWire distal protection device was inflated during percutaneous interventions of diseased vein grafts. Methods Forty consecutive patients undergoing vein graft stenting, all with successful delivery of the GuardWire system, were enrolled. All patients underwent 6-months follow-up angiography. Quantitative coronary angiographic analysis of the vein graft segment where the balloon was inflated was performed before and after the procedure, as well as at 6-month follow-up. Results No differences in reference vessel diameter, minimal luminal diameter and diameter stenosis were evident between the three measurements. In particular, the difference between post-procedural and follow-up minimal luminal diameter (namely late loss) was 0.003 ± 0.19 mm (95% confidence interval: − 0.06–0.06). Conclusions This prospective study supports for the first time the “angiographic safety” of low pressure inflations of a compliant balloon in saphenous vein grafts, suggesting the absence of acute and mid-term effects on the vein graft vessel wall.