Chronic phantom limb pain: the effects of calcitonin, ketamine, and their combination on pain and sensory thresholds

BACKGROUND: Calcitonin was effective in a study of acute phantom limb pain, but it was not studied in the chronic phase. The overall literature on N-methyl-D-aspartate antagonists is equivocal. We tested the hypothesis that calcitonin, ketamine, and their combination are effective in treating chronic phantom limb pain. Our secondary aim was to improve our understanding of the mechanisms of action of the investigated drugs using quantitative sensory testing. METHODS: Twenty patients received, in a randomized, double-blind, crossover manner, 4 i.v. infusions of: 200 IE calcitonin; ketamine 0.4 mg/kg (only 10 patients); 200 IE of calcitonin combined with ketamine 0.4 mg/kg; placebo, 0.9% saline. Intensity of phantom pain (visual analog scale) was recorded before, during, at the end, and the 48 h after each infusion. Pain thresholds after electrical, thermal, and pressure stimulation were recorded before and during each infusion. RESULTS: Ketamine, but not calcitonin, reduced phantom limb pain. The combination was not superior to ketamine alone. There was no difference in basal pain thresholds between the amputated and contralateral side except for pressure pain. Pain thresholds were unaffected by calcitonin. The analgesic effect of the combination of calcitonin and ketamine was associated with a significant increase in electrical thresholds, but with no change in pressure and heat thresholds. CONCLUSIONS: Our results question the usefulness of calcitonin in chronic phantom limb pain and stress the potential interest of N-methyl-D-aspartate antagonists. Sensory assessments indicated that peripheral mechanisms are unlikely important determinants of phantom limb pain. Ketamine, but not calcitonin, affects central sensitization processes that are probably involved in the pathophysiology of phantom limb pain.

Postmortem whole-body CT angiography: evaluation of two contrast media solutions

OBJECTIVE: The objective of our study was to establish a standardized procedure for postmortem whole-body CT-based angiography with lipophilic and hydrophilic contrast media solutions and to compare the results of these two methods. MATERIALS AND METHODS: Minimally invasive postmortem CT angiography was performed on 10 human cadavers via access to the femoral blood vessels. Separate perfusion of the arterial and venous systems was established with a modified heart-lung machine using a mixture of an oily contrast medium and paraffin (five cases) and a mixture of a water-soluble contrast medium with polyethylene glycol (PEG) 200 in the other five cases. Imaging was executed with an MDCT scanner. RESULTS: The minimally invasive femoral approach to the vascular system provided a good depiction of lesions of the complete vascular system down to the level of the small supplying vessels. Because of the enhancement of well-vascularized tissues, angiography with the PEG-mixed contrast medium allowed the detection of tissue lesions and the depiction of vascular abnormalities such as pulmonary embolisms or ruptures of the vessel wall. CONCLUSION: The angiographic method with a water-soluble contrast medium and PEG as a contrast-agent dissolver showed a clearly superior quality due to the lack of extravasation through the gastrointestinal vascular bed and the enhancement of soft tissues (cerebral cortex, myocardium, and parenchymal abdominal organs). The diagnostic possibilities of these findings in cases of antemortem ischemia of these tissues are not yet fully understood.

Comparison of neutral oral contrast versus positive oral contrast medium in abdominal multidetector CT

To determine whether neutral contrast agents with water-equivalent intraluminal attenuation can improve delineation of the bowel wall and increase overall image quality for a non-selected patient population, a neutral oral contrast agent (3% mannitol) was administered to 100 patients referred for abdominal multidetector row computed tomography (MDCT). Their results were compared with those of 100 patients given a positive oral contrast agent. Qualitative and quantitative measurements were done on different levels of the gastrointestinal tract by three experienced readers. Patients given the neutral oral contrast agent showed significant better qualitative results for bowel distension (P < 0.001), homogeneity of the luminal content (P < 0.001), delineation of the bowel-wall to the lumen (P < 0.001) and to the mesentery (P < 0.001) and artifacts (P < 0.001), leading to a significant better overall image quality (P < 0.001) than patients receiving positive oral contrast medium. The quantitative measurements revealed significant better distension (P < 0.001) and wall to lumen delineation (P < 0.001) for the patients receiving neutral oral contrast medium. The present results show that the neutral oral contrast agent (mannitol) produced better distension, better homogeneity and better delineation of the bowel wall leading to a higher overall image quality than the positive oral contrast medium in a non-selected patient population.

Adequacy of an early arterial phase low-volume contrast protocol in 64-detector computed tomography angiography for aortoiliac aneurysms

PURPOSE: This retrospective study was conducted to determine whether a low-volume contrast medium protocol provides sufficient enhancement for 64-detector computed tomography angiography (CTA) in patients with aortoiliac aneurysms. METHODS: Evaluated were 45 consecutive patients (6 women; mean age, 72 +/- 6 years) who were referred for aortoiliac computed tomography angiography between October 2005 and January 2007. Group A (22 patients; creatinine clearance, 64.2 +/- 8.1 mL/min) received 50 mL of the contrast agent. Group B (23 patients; creatinine clearance, 89.4 +/- 7.3 mL/min) received 100 mL of the contrast agent. The injection rate was 3.5 mL/s, followed by 30 mL of saline at 3.5 mL/s. Studies were performed on the same 64-detector computed tomography scanner using a real-time bolus-tracking technique. Quantitative analysis was performed by determination of mean vascular attenuation at 10 regions of interest from the suprarenal aorta to the common femoral artery by one reader blinded to type and amount of contrast agent and compared using the Student t test. Image quality according to a 4-point scale was assessed in consensus by two readers blinded to type and amount of contrast medium and compared using the Mann-Whitney test. Multivariable adjustments were performed using ordinal regression analysis. RESULTS: Mean total attenuation did not differ significantly between both groups (196.5 +/- 33.0 Hounsfield unit [HU] in group A and 203.1 +/- 44.2 HU in group B; P = .57 by univariate and P > .05 by multivariable analysis). Accordingly, attenuation at each region of interest was not significantly different (P > .35). Image quality was excellent or good in all patients. No significant differences in visual assessment were found comparing both contrast medium protocols (P > .05 by univariate and by multivariable analysis). CONCLUSIONS: Aortoiliac aneurysm imaging can be performed with substantially reduced amounts of contrast medium using 64-detector computed tomography angiography technology.

Quantitative stress echocardiography in coronary artery disease using contrast-based myocardial blood flow measurements: prospective comparison with coronary angiography

AIM: To test whether quantitative stress echocardiography using contrast-based myocardial blood flow (MBF, ml x min(-1) x g(-1)) measurements can detect coronary artery disease in humans. METHODS: 48 patients eligible for pharmacological stress testing by myocardial contrast echocardiography (MCE) and willing to undergo subsequent coronary angiography were prospectively enrolled in the study. Baseline and adenosine-induced (140 microg x kg(-1) x min(-1)) hyperaemic MBF was analysed according to a three-coronary-artery-territory model. Vascular territories were categorised into three groups with increasing stenosis severity defined as percentage diameter reduction by quantitative coronary angiography. RESULTS: Myocardial blood flow reserve (MBFR)-that is, the ratio of hyperaemic to baseline MBF, was obtained in 128 (89%) territories. Mean (SD) baseline MBF was 1.073 (0.395) ml x min(-1) x g(-1) and did not differ between territories supplied by coronary arteries with mild (<50% stenosis), moderate (50%-74% stenosis) or severe (>or=75% stenosis) disease. Mean (SD) hyperaemic MBF and MBFR were 2.509 (1.078) ml x min(-1) x g(-1) and 2.54 (1.03), respectively, and decreased linearly (r2 = 0.21 and r2 = 0.39) with stenosis severity. ROC analysis revealed that a territorial MBFR <1.94 detected >or=50% stenosis with 89% sensitivity and 92% specificity. CONCLUSION: Quantitative stress testing based on MBF measurements derived from contrast echocardiography is a new method for the non-invasive and reliable assessment of coronary artery disease in humans.

Magnetization transfer contrast and T2 mapping in the evaluation of cartilage repair tissue with 3T MRI

PURPOSE: To use magnetization transfer (MT) imaging in the visualization of healthy articular cartilage and cartilage repair tissue after different cartilage repair procedures, and to assess global as well as zonal values and compare the results to T2-relaxation. MATERIALS AND METHODS: Thirty-four patients (17 after microfracture [MFX] and 17 after matrix-associated autologous cartilage transplantation [MACT]) were examined with 3T MRI. The MT ratio (MTR) was calculated from measurements with and without MT contrast. T2-values were evaluated using a multiecho, spin-echo approach. Global (full thickness of cartilage) and zonal (deep and superficial aspect) region-of-interest assessment of cartilage repair tissue and normal-appearing cartilage was performed. RESULTS: In patients after MFX and MACT, the global MTR of cartilage repair tissue was significantly lower compared to healthy cartilage. In contrast, using T2, cartilage repair tissue showed significantly lower T2 values only after MFX, whereas after MACT, global T2 values were comparable to healthy cartilage. For zonal evaluation, MTR and T2 showed a significant stratification within healthy cartilage, and T2 additionally within cartilage repair tissue after MACT. CONCLUSION: MT imaging is capable and sensitive in the detection of differences between healthy cartilage and areas of cartilage repair and might be an additional tool in biochemical cartilage imaging. For both MTR and T2 mapping, zonal assessment is desirable.

Whole body postmortem angiography with a high viscosity contrast agent solution using poly ethylene glycol as contrast agent dissolver

Postmortem minimal invasive angiography has already been implemented to support virtual autopsy examinations. An experimental approach in a porcine model to overcome an initially described artificial tissue edema artifact by using a poly ethylene glycol (PEG) containing contrast agent solution showed promising results. The present publication describes the first application of PEG in a whole corpse angiographic CT examination. A minimal invasive postmortem CT angiography was performed in a human corpse utilizing the high viscosity contrast agent solution containing 65% of PEG. Injection was carried out via the femoral artery into the aortic root in simulated cardiac output conditions. Subsequent CT scanning delivered the 3D volume data of the whole corpse. Visualization of the human arterial anatomy was excellent and the contrast agent distribution was generally limited to the arterial system as intended. As exceptions an enhancement of the brain, the left ventricular myocardium and the renal cortex became obvious. This most likely represented the stage of centralization of the blood circulation at the time of death with dilatation of the precapillary arterioles within these tissues. Especially for the brain this resulted in a distinctively improved visualization of the intracerebral structures by CT. However, the general tissue edema artifact of postmortem minimal invasive angiography examinations could be distinctively reduced.

In contrast to lung fibroblasts--no signs of senescence in skin fibroblasts of patients with emphysema

Smoking is known to be linked to skin ageing and there is evidence for premature senescence of parenchymal lung fibroblasts in emphysema. To reveal whether the emphysema-related changes in cellular phenotype extend beyond the lung, we compared the proliferation characteristics of lung and skin fibroblasts between patients with and without emphysema. Parenchymal lung fibroblasts and skin fibroblasts from the upper torso (thus limiting sun exposure bias) were obtained from patients without, or with mild, or with moderate to severe emphysema undergoing lung surgery. We analysed proliferation rate, population doublings (PD), staining for senescence-associated beta-galactosidase (beta-gal) and gene expression of IGFBP-3 and IGFBP-rP1. Population doubling time of lung fibroblasts differed between control, mild, and moderate to severe emphysema (median (IQR) 29.7(10.0), 33.4(6.1), 44.4(21.2) h; p=0.012) and staining for beta-gal was elevated in moderate to severe emphysema. Compared to control subjects, skin fibroblasts from patients with emphysema did not differ with respect to proliferation rate, PD and beta-gal staining, and showed a lower abundance of mRNA for IGFBP-3 and -rP1 (p<0.05, each). These results suggest that the induction of a senescent fibroblast phenotype by cigarette smoke, as observed in emphysema, primarily occurs in the lung.

Impact of coil position and electrophysiological monitoring on determination of motor thresholds to transcranial magnetic stimulation

OBJECTIVE: We compared motor and movement thresholds to transcranial magnetic stimulation (TMS) in healthy subjects and investigated the effect of different coil positions on thresholds and MEP (motor-evoked potential) amplitudes. METHODS: The abductor pollicis brevis (APB) 'hot spot' and a standard scalp position were stimulated. APB resting motor threshold (APB MEP-MT) defined by the '5/10' electrophysiological method was compared with movement threshold (MOV-MT), defined by visualization of movements. Additionally, APB MEP-MTs were evaluated with the '3/6 method,' and MEPs were recorded at a stimulation intensity of 120% APB MEP-MT at each position. RESULTS: APB MEP-MTs were significantly lower by stimulation of the 'hot spot' than of the standard position, and significantly lower than MOV-MTs (n=15). There were no significant differences between the '3/6' and the '5/10' methods, or between APB MEP amplitudes by stimulating each position at 120% APB MEP-MT. CONCLUSIONS: Coil position and electrophysiological monitoring influenced motor threshold determinations. Performing 6 instead of 10 trials did not produce different threshold measurements. Adjustment of intensity according to APB MEP-MT at the stimulated position did not influence APB MEP amplitudes. SIGNIFICANCE: Standardization of stimulation positions, nomenclature and criteria for threshold measurements should be considered in design and comparison of TMS protocols.

Renal artery assessment with nonenhanced steady-state free precession versus contrast-enhanced MR angiography

PURPOSE: To prospectively assess the diagnostic accuracy of nonenhanced three-dimensional (3D) steady-state free precession (SSFP) magnetic resonance (MR) angiography for detection of renal artery stenosis (RAS), with breath-hold contrast material-enhanced MR angiography performed as the reference standard. MATERIALS AND METHODS: The study was local ethics committee approved; all patients gave written informed consent. Fifty-three patients (30 male, 23 female; mean age, 58 years) with arterial hypertension and suspected of having RAS were examined with 1.5-T 3D SSFP renal MR angiography. Stenosis grade, maximal visible vessel length, and subjective image quality were compared. Sensitivity, specificity, accuracy, and negative predictive value (NPV) were calculated on artery-by-artery and patient-by-patient bases. The significance of the results was assessed with the paired two-sided t test for continuous variables and with the marginal homogeneity test for categorical variables. Cohen kappa statistics were used to estimate interobserver agreement. RESULTS: One hundred eight renal arteries with 20 significant (>or=50%) stenoses were detected with contrast-enhanced MR angiography. At artery-by-artery analysis, sensitivity, specificity, accuracy, and NPV of nonenhanced SSFP MR angiography for RAS detection were 100%, 93%, 94%, and 100%, respectively, for observer 1 and 95%, 95%, 95%, and 99%, respectively, for observer 2. Corresponding patient-by-patient values were 100%, 92%, 94%, and 100%, respectively, for observer 1 and 100%, 95%, 96%, and 100%, respectively, for observer 2. Overestimation of stenosis grade with SSFP MR angiography resulted in six and four false-positive findings for readers 1 and 2, respectively. Mean maximal visible lengths of the renal arteries were 69.9 mm at contrast-enhanced MR angiography and 61.1 mm at SSFP MR angiography (P<.001). Both techniques yielded good to excellent image quality. CONCLUSION: Slab-selective inversion-prepared 3D SSFP MR angiography had high sensitivity, specificity, accuracy, and NPV for RAS detection, without the need for contrast material. However, RAS severity was overestimated in some patients.

Myocardial contrast echocardiography for the distinction of hypertrophic cardiomyopathy from athlete's heart and hypertensive heart disease

BACKGROUND: Myocardial contrast echocardiography (MCE) is able to measure in vivo relative blood volume (rBV, i.e., capillary density), and its exchange frequency b, the constituents of myo-cardial blood flow (MBF, ml min-1 g-1). This study aimed to assess, by MCE, whether left ventricular hypertrophy (LVH) in hypertrophic cardiomyopathy (HCM) can be differentiated from LVH in triathletes (athlete's heart, AH) or from hypertensive heart disease patients (HHD). METHODS: Sixty individuals, matched for age (33 +/- 10 years) and gender, and subdivided into four groups (n = 15) were examined: HCM, AH, HHD and a group of sedentary individuals without LVH (S). rBV (ml ml-1), b (min-1) and MBF, at rest and during adenosine-induced hyperaemia, were derived by MCE in mid septal, lateral and inferior regions. The ratio of MBF during hyperaemia and MBF at rest yielded myocardial blood flow reserve (MBFR). RESULTS: Septal wall rBV at rest was lower in HCM (0.084 +/- 0.023 ml ml-1) than in AH (0.151 +/- 0.024 ml ml-1, p <0.01) and in S (0.129 +/- 0.026 ml ml-1, p <0.01), but was similar to HHD (0.097 +/- 0.016 ml ml-1). Conversely, MBFR was lowest in HCM (1.67 +/- 0.93), followed by HHD (2.8 +/- 0.93, p <0.01), by S (3.36 +/- 1.03, p <0.001) and by AH (4.74 +/- 1.46, p <0.0001). At rest, rBV <0.11 ml ml-1 accurately distinguished between HCM and AH (sensitivity 99%, specificity 99%), similarly MBFR < or =1.8 helped to distinguish between HCM and HHD (sensitivity 100%, specificity 77%). CONCLUSIONS: rBV at rest, most accurately distinguishes between pathological LVH due to HCM and physiological, endurance-exercise induced LVH.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Detection of pulmonary emboli with CT angiography at reduced radiation exposure and contrast material volume: comparison of 80 kVp and 120 kVp protocols in a matched cohort

The detection rate of pulmonary emboli (PE) with computed tomography angiography (CTA) using either a standard or a low-dose protocol, combining reduced radiation exposure and iodine delivery rate, was retrospectively analyzed in a matched cohort of 120 patients.