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Utility of Doppler-detectable microbubbles in the diagnosis and treatment of decompression sickness.

BACKGROUND: Doppler-detectable microbubbles (DMB) are frequently used to evaluate altitude decompression stress. However, the role of DMB in the therapy of decompression sickness (DCS) has not been examined. HYPOTHESIS: The ability of Doppler to detect microbubbles during decompression (Doppler test) may be used in the diagnosis of DCS, and to aid clinical decisions about treatment options for DCS. METHODS: We examined the data on DMB and symptoms from NASA Database on DCS (n = 516). The accuracy of Doppler test was obtained from the Receiver Operating Characteristic (ROC) for DMB (grades I through IV), and efficacy was obtained by calculating predictive or post-test probabilities. Threshold analysis was used to obtain the probabilities for testing and/or treatment decisions. RESULTS: The Doppler test was useful for both screening and confirming DCS, when different criteria (grade I for screening; grade IV for confirming) were used for a positive test. Calculation of predictive values and threshold analysis showed that: 1) early recompression was the therapy of choice when post-test probability of disease was > 0.25 in individuals with non-specific pain at altitude, and early recompression with 100% oxygen for 2 h at site level was optimal therapy when this probability was > 0.33; 2) hyperbaric therapy was optimal when post-test probability was > 0.04 in individuals with uncertain symptoms post-flight. CONCLUSIONS: The Doppler test was of greater utility in excluding DCS than confirming its presence, and was useful in making therapeutic decisions on DCS when confronted with non-specific symptoms at altitude.

Aerospace Medicine↗

The effect of hyperbaric oxygen therapy on a burn wound model in human volunteers.

A previous nonblinded study has suggested beneficial effects from hyperbaric oxygen treatment of superficial partial-thickness radiation burns in human volunteers. This protocol was designed to either confirm or challenge these previous findings in a randomized, blinded format. Twelve healthy, nonsmoking volunteers (7 males, 5 females) participated. All were screened for contraindications to hyperbaric oxygen therapy (acute sinusitis, otitis media, pneumonia, pregnancy, active cancer, pneumothorax) and given a single test hyperbaric exposure. A standardized wound model was employed for the painless creation of a volar forearm lesion on volunteers by applying a suction device to form a blister, excising its epidermal roof, and irradiating the exposed dermis with ultraviolet light. Subjects were randomized into either a hyperbaric oxygen group (100% oxygen at 2.4 ATA, n = 6) or the sea-level air-breathing equivalent control group (8.75% oxygen at 2.4 ATA, n = 6). Both groups then underwent standard hyperbaric therapy. The subjects, the hyperbaric oxygen chamber operators, and the monitoring clinicians were all blinded to the oxygen concentration administered. Each subject received two dives per day over a 3-day period. The wounds were studied noninvasively prior to treatment and once per day over 6 days for size, hyperemia, and exudation, with epithelialization as the endpoint. The averages for each measurement of the hyperbaric oxygen group versus the control group were computed by means of a one-tail t test; p was considered significant at less than 0.05. Daily wound size, hyperemia, and exudation measurements were significantly different on day 2. The hyperbaric oxygen group showed a 42 percent reduction in wound hyperemia, a 35 percent reduction in the size of the lesion, and a 22 percent reduction in wound exudation (p values of 0.05, 0.03, and 0.04, respectively). No significant difference was noted for epithelialization. Observed differences in wound size, hyperemia, and exudation were attributable to hyperbaric oxygen therapy. This study further supports earlier conclusions that hyperbaric oxygen therapy is beneficial in a superficial dermal wound.

Blood Flow Velocity↗

[Tissue oxygenation and microcirculation in dermatoliposclerosis with different degrees of erythema at the margins of venous ulcers. A contribution to hypodermitis symptoms].

BACKGROUND: In patients with chronic venous insufficiency erythematous areas in indurated skin (hypodermitis) and non erythematous areas of lipodermatosclerosis were examined. METHODS: In 13 patients with venous ulcers a total of 32 localizations in more or less erythematous and indurated ulcer edges were measured. The amount of erythema was taken as an indicator for the extent of hypodermitis. The parameters examined were erythema (a-value), skin temperature (t), laser Doppler flow (LDF), transcutaneous (tcpO2) and intracutaneous oxygen tension (icpO2). According to the amount of erythema the different localizations were separated into two groups: areas with a-values lower than 14,2 were classified as lipodermatosclerosis without or with little erythema, are-as with a-values higher than 14,2 were classified as areas of lipodermatosclerosis with extensive erythema. Identical measurements were also performed in healthy looking skin below the knee. RESULTS: Skin temperature and LDF were higher in areas with much erythema compared to those with little or no erythema. TcpO2, measured with an electrode temperature of 44 degrees C, was lower in areas with inflammation; tcpO2-values at 37 degrees C and icpO2-values showed no differences in ulcer edges with different amounts of inflammation. CONCLUSION: The results show differences of microcirculation between areas of lipodermatosclerosis with and without hypodermitis. These differences did not influence the actual tissue oxygenation in deeper parts in the dermis.

Aged↗

Protection from radiation-induced alopecia with topical application of nitroxides: fractionated studies.

PURPOSE: Hair loss resulting from irradiation of the head and neck or from whole brain irradiation often leads to cosmetic, social, and psychological problems for the radiotherapy patient. Few successful clinical interventions are available. We have shown that nitroxides (stable free radicals) afford radiation protection against single-dose radiation-induced alopecia in a guinea pig model. Here we determine if topical nitroxide application provides protection from fractionated radiation treatment. MATERIALS AND METHODS: Two symmetrical and contralateral areas (3 x 5 cm) of skin on the dorsal trunk of guinea pigs were shaved to a hair length of 0.25 cm. A 2 mL solution containing 70 mg/mL nitroxide (Tempo or Tempol) in 70% ethanol was topically applied to the skin surface of one side; 70% ethanol was applied to the contralateral (control) side 10 minutes before irradiation. Animals were placed in a special jig that held skin without decreasing blood flow to the treatment area and fractionated external beam radiation (7 Gy) was delivered daily for eight fractions over 10 days via a 4 MeV linear accelerator. Alopecia (hair density) was scored weekly for 13 to 14 weeks after radiotherapy, using a standardized reference with respect to hair loss and regrowth in the treatment field. RESULTS: After radiation treatment, dry desquamation and gradual hair loss were observed for both control and nitroxide-treated skin; however, over weeks 4 to 11 postirradiation hair loss was much more pronounced in control animals when compared with nitroxide-treated animals. Hair density measurements for Tempol treatment over weeks 9 to 13 were approximately 75% compared with measurements in controls of approximately 25%. Tempo-treated animals exhibited hair density values of approximately 90% compared with 12% in controls over weeks 11 to 14. Tempol and Tempo treatments resulted in significant radioprotection. Histologic evaluation showed that radiation treatment alone in ethanol controls resulted in a marked decrease in the number of hair follicles and poor development of remaining follicles; however, nitroxide pretreatment resulted in no appreciable decrease in hair follicles and hair follicles appeared mature. This was also observed in unirradiated ethanol controls. Electron paramagnetic resonance studies revealed that topical nitroxide application did not result in measurable systemic concentrations of either drug. CONCLUSIONS: The results of this study suggest that topical application of nitroxides may be useful in a clinical setting to reduce the undesirable toxicity of radiation-induced alopecia.

Administration, Topical↗

Implantable hearing device performance measured by laser Doppler interferometry.

Recent application of the Doppler principle laser interferometry to audiology, acoustics and otology has facilitated the development of implantable hearing devices (IHDs). During the design and testing of two different electromagnetic middle ear implants for sensorineural hearing loss, we used single-point laser Doppler interferometry (LDI). A commercially available interferometer, internally calibrated and validated against a National Institute for Standards and Technology (NIST) standard, was used with both mechanical fixtures and fresh temporal bones to evaluate implant mass, shape and orientation, attachment, electromagnetic coupling and acoustic properties. At both Hough Ear Institute and Symphonix Devices, Inc., we have shown that high fidelity and amplitudes can be recorded in vitro over a frequency range of 500 Hz to 10 kHz. These data can provide greater assurance of safety and efficacy to regulatory agencies before entering clinical trials. We propose that LDI be considered as an international standard for accurate, consistent comparison of performances of all IHDs during development. Furthermore, the future availability of human IHD data will allow for the extrapolation of a mechanical bench model of the middle ear transfer function for use in quality control during manufacturing and diagnosis of failure in IHDs.

Cochlear Implants↗

Skin hyperemia in a habitual blusher.

Blushing, a vascular skin response to emotion is difficult to investigate since subjects are not able to blush on demand in a laboratory setting. Laser Doppler fluxmetry measures blood flux changes noninvasively. In a 28 year old lady distressed by habitual blushing we were able to document changes in skin blood flux during blushing. Forehead skin blood flux increased suddenly from 20 to 45 arbitrary units and returned to baseline values after about 3 minutes. It is the first time that emotionally provoked hyperemia in head skin is documented.

Blushing↗

Acute ethanol effects on focal cerebral ischemia in nonfasted rats.

Focal cerebral ischemia was induced in a rat model of middle cerebral artery occlusion. Three groups of adult male Sprague-Dawley rats, given food and water ad libitum, were subjected to 4 hr of middle cerebral artery occlusion. All were given vehicle control and ethanol pretreatments intraperitoneally 1 hr before. Mean ipsilateral brain water content in the control, 2 g/kg ethanol, and 2 g/kg ethanol + insulin-treated groups showed: ischemia core: 81.1%, 82.5%, and 80.9%; intermediate zone: 81.0%, and 80.3%; and outer zone: 80.3%, 81.3%, and 80.1%, respectively. Brain Na+ and K4 content in these groups paralleled the water content. In addition to significantly (p < 0.05) more brain edema, the 2 g/kg ethanol-treated animal group also had significant hyperglycemia. In contrast, the 2 g/kg ethanol + insulin-treated animals were normoglycemic and had ischemic, intermediate, and outer zone Na+, K+, and Cl- levels comparable with the control group (p > 0.05). These results stress the importance of measuring and controlling plasma glucose levels in the in vivo studies of the neurotoxic effects of acute ethanol.

Alcoholic Intoxication↗

[Hand ischemia due to "steal syndrome" in vascular access for hemodialysis].

Among complications of vascular access operations, symptomatic steal syndrome is uncommon, but may lead to ischemia of the hand. Between 1983 and 1995, 5 patients with hemodialysis fistulas presented rest pain of finger necrosis with a wrist-brachial index of 0.56 (range 0.35 to 0.63) improving to 0.96 (range 0.72 to 1.05) after digital pressure of the fistula. Ligation of distal radial artery was performed in 3 patients with side-to-end radiocephalic fistula, while basilic vein was distally ligated in a case of side-to-side brachiobasilic fistula. A vein "banding" procedure reduce fistula flow and improved distal perfusion in one patient, while a true venous aneurysm of the cephalic vein was treated by excision and replacement with a tapered PTFE graft. Hemodynamic assessment is required during surgical correction, but it may also be useful in pre- and intra-operative evaluation of patients undergoing therapeutical AVFs to prevent arterial insufficiency of the hand.

Adult↗

Reproducibility of retinal and optic nerve head blood flow measurements with scanning laser Doppler flowmetry.

PURPOSE: To evaluate the interobserver variability and the reproducibility of retinal and optic nerve head capillary blood flow measurements performed with a new noninvasive equipment, the scanning laser Doppler flowmeter (Heidelberg Engineering, Heidelberg, Germany). METHODS: Blood flow measurements were performed during three independent sessions in six patients with glaucoma and five normal subjects using the scanning laser Doppler flowmeter (SLDF), which allows the visualization of perfused capillaries and vessels of the retina and optic nerve head and enables the quantification of capillary blood volume, flow, and velocity in any selected area of the perfusion map. To evaluate the interobserver variability in selecting the areas in the perfusion map to be measured, three observers tried to locate the same areas in the perfusion map of images obtained during the first session. To evaluate the reproducibility of the measurements, the observers measured correspondent areas in the peripapillary retina and in the optic nerve head of images from the three sessions. Areas of different sizes (10 x 10 pixels and 4 x 4 pixels) were measured. RESULTS: The agreement between readings performed by the three observers was very good, with the reliability coefficient for the various parameters varying from 0.90 to 0.98. The reproducibility of retinal and lamina cribrosa measurements with the 10 x 10 pixel square target was good (reliability coefficient for the different parameters ranging from 0.70 to 0.85) and much better than the reproducibility of the 4 x 4 pixel target. The measurements performed in the neuroretinal rim area also had poor reproducibility. The measurements from the patients with glaucoma tended to be more reproducible than those from normal subjects. CONCLUSIONS: The SLDF allows reproducible blood perfusion measurements of retinal and lamina cribrosa areas when a target square of 10 x 10 pixels is used.

Adult↗

Effects of adrenergic stimulation on sciatic nerve blood flow in diabetic and control rats.

Sciatic endoneurial blood flow is reduced in experimental diabetes. This study examined the possible involvement of noradrenergic mechanisms in this impairment. In anaesthetised rats (pentobarbitone sodium 50 mg/kg, diazepam 2 mg/kg), sciatic nerve laser Doppler flux and vascular resistance in diabetic rats (5-6 weeks) were lower (approximately 50%) and higher (approximately 42%), respectively, than that in age-matched control rats, indicating nerve ischaemia in the diabetic tissues. Tyramine (1 nmol), noradrenaline (0.001-1 nmol) and phenylephrine (0.01-10 nmol) produced significant increases of nerve vascular resistance in control rats. The responses to tyramine (1 nmol) were completely blocked by desipramine (10 nmol) and those to phenylephrine (10 nmol) were reversed by phentolamine (1 nmol). In streptozotocin-diabetic rats, responses to phenylephrine or noradrenaline were enhanced compared to control rats, but the enhancement failed to reach statistical significance. The findings demonstrate that adrenergic stimulation affects sciatic nerve endoneurial blood flow.

Adrenergic alpha-Agonists↗

[Functional role of muscarinic M1 receptor for the ganglionic transmission in the rat superior cervical ganglion].

To elucidate the sympathetic ganglia transmission via muscarinic M1 receptor subtype, we focused on the external carotid nerve (ECN), which branches from the superior cervical ganglion and innervates the thyroid gland. In addition, thyroid blood flow (TBF) was measured by a Laser Doppler blood flow meter as an indicator for the function of ECN. A relatively specific M1 agonist, AF102B, elicited a burst depolarization of ECN and an increase in TBF. Pretreatment with a selective M1 antagonist, pirenzepine, inhibited these responses. Superior cervical ganglionectomy also suppressed the AF102B-induced increase in TBF. In contrast, electric stimulation of the sympathetic trunk elicited a TBF decrease. Nicotinic receptor agonist, DMPP (dimethylphenylpiperazinium) evoked a short-term ECN depolarization, but decreased the TBF. These responses were blocked by nicotinic receptor antagonist, hexamethonium (C6), but not only by pirenzepine. Pretreatment with nitric oxide (NO) synthase inhibitor, L-NAME, suppressed the AF102B-induced increase in TBF. These findings suggest that the M1 receptor subtype may modulate the sympathetic ganglionic transmission which has a mechanism different from nicotinic transmission in terms of functional roles, i.e., blood flow changes. Furthermore, the NO system might be involved in sympathetic ganglia transmission via the M1 receptor subtype in the rat cervical ganglion.

Animals↗

[Evaluation on blood clearance and hepatic uptake of 99mTc-GSA in rats with blood flow conversion].

This study was aimed to clarify a contribution of the hepatic blood flow in hepatic accumulation of 99mTc-DTPA-galactosyl serum albumin (99mTc-GSA). The experiment was performed in rats by the blood flow conversion with an external scintillation gamma camera and laser doppler flowmeter. Rats were divided into 4 groups: hepatic artery ligation (HAL, n = 10), portal vein ligation (PVL, n = 8), both hepatic artery and portal vein ligation (HAL+PVL, n = 9), and control (CONT, n = 10) groups. The scintigraphic data were obtained in each group for 10 minutes after intravenous injection of 99mTc-GSA (50 micrograms/100 g B.W). The regions of interest were assigned over the heart and whole liver and the time activity curves (TAC) were generated. Five parameters of HH 4, LHL 4, KH1, KH2, KL, were calculated as blood clearance and hepatic accumulation from TAC in each rat. HH4 as blood clearance index in CONT, HAL, PVL and HAL+PVL was 0.58 +/- 0.04 (mean +/- SE), 0.63 +/- 0.04, 0.85 +/- 0.04, 0.97 +/- 0.001, respectively. HH 4 between CONT vs PVL, HAL+PVL was statistically significant (p < 0.05). LHL 4 as hepatic uptake index in CONT, HAL, PVL and HAL+PVL was 0.96 +/- 0.001, 0.93 +/- 0.01, 0.71 +/- 0.07, 0.41 +/- 0.04, respectively. This parameter was also statistically significant between CONT vs PVL and HAL+PVL groups. Another parameter of KH1 for blood clearance and KL for hepatic uptake were also significant between CONT vs PVL and HAL+PVL groups. All parameters obtained in 99mTc-GSA study correlated well with the hepatic flow rate which was measured with a laser doppler flowmeter and reflected the reduction rate of the hepatic tissue blood flow 4 minutes after the ligation of target vessels. These result suggest that blood clearance and hepatic uptake of 99mTc-GSA are significantly affected by hepatic blood inflow. 99mTc-GSA scintigraphy may be useful in evaluating hepatic tissue blood flow.

Animals↗

[Microcirculatory changes in mitral prolapse as an expression of a systemic change in the connective tissue].

Many authors hypothesize that mitral valve prolapse (MVP) can be, in most cases, only a clinical sign of a primitive and systemic disorder of the connective tissue, like in Marfan Syndrome (MS). In our previous works we supported the presence of morphological and functional alterations of the microcirculation in patients affected by MS. In order to characterize a possible common denominator between these pathologies we have studied the cutaneous microcirculation in a group of patients affected by MVP, divided into 2 groups: anatomic MVP (MVP) and MVP syndrome (MVPS). The morphologic parameters have been investigated by nailfold capillaroscopy while digital laser-Doppler was used to study skin flowmetry. The results have been compared with a control group. Capillaroscopic remarkers showed an architecturally disorganized microvasculature with aspects related to a reduced compactness of the microvasculature unit with a significatively higher score compared with controls (7.3 +/- 2.9 vs 3.6 +/- 1 p less than 0.0005). Laser-Doppler flowmetry showed a significatively reduced rest flow; ischemic test showed: spike time 48.9 +/- 36.9 vs 15.3 +/- 7.7 s (p less than 0.0005), hyperemic acme 6.6 +/- 2.7 vs 12.5 +/- 8.4 UP (p less than 0.002); % increase 32.1 +/- 20.2 vs 51.5 +/- 15.4 (p less than 0.002). Thermic test showed a significatively higher thermic acme 8.7 +/- 4.2 vs 12.6 +/- 9.11 UP (p less than 0.05). These results appeared to be correlated with stage pathology as it was observed a severe microvasculature disorders in MVPS. Therefore we suppose that a phenotypic continuum may exist between MS and MVP.

Adult↗

Effects of neural blockade and general anesthesia on the laser-Doppler skin blood flow waves recorded from the finger or toe.

Effects of neural blockade and general anesthesia on the basic wave (BW) and the reflex wave (RW) among the laser-Doppler (L-D) skin blood flow waves recorded on the finger or toe were studied in 2 volunteers and 42 patients. The BW was continuous, rhythmic and independent of respiratory movements. The RW, which was induced by a deep inspiration or a snapping sound, was a transient marked reduction in blood flow. The BW was almost flattened and the RW was no longer induced at the finger under complete wrist block (n = 2), or under cervical or upper thoracic epidural anesthesia extended caudally over T7 (n = 2). On the other hand, the BW was still detected with reducing frequency and the RW could be provoked with one exception at the finger on the side with a sympathetic ganglion block at the C6 vertebral level (n = 14). The BW and RW at the toe were retained under lumbar subdural anesthesia (n = 6) as well. However, under the combination of lumbar subdural anesthesia and lower thoracic epidural anesthesia extending rostrally over T4 (n = 6), both the BW and the RW disappeared at the toe. In the course of deepening nitrous oxide/enflurane anesthesia (n = 10), the BW gradually reduced in frequency until it was almost flattened, and it became difficult to provoke the RW. L-D flowmetry of the finger or toe could be a useful clinical measure for detecting the presence or absence of sympathetic function controlling cutaneous vasomotion.

Adult↗

Current status of noninvasive tests in the diagnosis of peripheral arterial disease.

In this review of the current status of the vascular laboratory, the major emphasis has been upon those tests that have become well-established and documented, including resting pressure, pulse volume measurements, velocity studies, and three stress measurements--exercise ankle pressure, postocclusive reactive hyperemia, and the toe pulse reappearance time. Additional technology that may have application to peripheral arterial disease includes photoplethysmography, transcutaneous oxygen tension, laser-Doppler velocimetry, fluorescein angiography, infrared thermography, and transcutaneous electromagnetic flowmetry. These techniques, which are currently in development and experimental trial, were not discussed but are likely to provide significant additional information. The future role of the vascular diagnostic laboratory in the area of peripheral arterial occlusive disease appears clear. It has already become a standard resource of the community hospital and tertiary referral center. Its functions will become more and more generally accepted with time as newly graduating physicians who have been exposed to this technology enter the practice of medicine. It should permit obtaining an evaluation of all patients at the expert level, aid in the education of all physicians concerned with peripheral arterial disease, and play an important part in guaranteeing a higher level of patient care than has heretofore been available.

Arterial Occlusive Diseases↗

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