Search

Objective: To assess the diagnostic accuracy of laser Doppler flowmetry (LDF) with mercury-in-silastic strain gauge plethysmography (SGP) as a reference test for measuring the toe and ankle pressures in patients with known or suspected peripheral arterial disease (PAD)., Methods: This was a prospective, randomized, blinded diagnostic accuracy study. Toe and ankle pressures were measured using both methods in 200 consecutive patients, who were recruited at our vascular laboratory over a period of 30 working days. Classification of PAD and critical limb ischemia (CLI) was made in accordance with TASC-II criteria., Results: The LDF method demonstrated 5.8 mm Hg higher mean toe pressures than the SGP method for the right limb and 7.0 mm Hg for the left limb (both P < .001). There were no significant differences in the mean ankle pressures (both P > .129). The limits of agreement for the differences (SGP - LDF) were -31.7 to 20.2 mm Hg for right toe pressures, -28.0 to 14.0 mm Hg for left toe pressures, -25.5 to 22.8 mm Hg for right ankle pressures, and -26.9 to 24.6 mm Hg for left ankle pressures. A correlation analysis of the absolute pressures using the two methods showed an intraclass correlation coefficient of 0.902 (95% confidence interval [CI], 0.835-0.938) for right toe pressures, 0.919 (95% CI, 0.782-0.960) for the left toe pressures, 0.953 (95% CI, 0.937-0.965) for right ankle pressures, and 0.952 (95% CI, 0.936-0.964) for left ankle pressures. Cohen's Kappa showed an agreement in the diagnostic classification of κ = 0.775 (95% CI, 0.631-0.919) for PAD and κ = 0.780 (95% CI, 0.624-0.936) for CLI., Conclusions: LDF showed a good correlation with SGP over a wide range of toe and ankle pressures, as well as substantial agreement for the diagnostic classification of PAD including CLI., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background/aims: The purpose of the present pilot study was to investigate the feasibility of combining large pore dermal microdialysis with shotgun proteomic analysis in human skin., Methods: Dialysate was recovered from human skin by 2000 kDa microdialysis membranes from one subject at three different phases of the study; trauma due to implantation of the dialysis device, a post implantation steady-state period, and after induction of vasodilatation and plasma extravasation. For shotgun proteomics, the proteins were extracted and digested with trypsin. Peptides were separated by capillary and nanoflow HPLC systems, followed by tandem mass spectrometry (MS/MS) on a Quadrupole-TOF hybrid instrument. The MS/MS spectra were merged and mapped to a human target protein database to achieve peptide identification and protein inference., Results: Results showed variation in protein amounts and profiles for each of the different sampling phases. The total protein concentration was 1.7, 0.6, and 1.3 mg/mL during the three phases, respectively. A total of 158 different proteins were identified. Immunoglobulins and the major classes of plasma proteins, including proteases, coagulation factors, apolipoproteins, albumins, and complement factors, make up the major load of proteins in all three test conditions., Conclusion: Shotgun proteomics allowed the identification of more than 150 proteins in microdialysis samples from human skin. This highlights the opportunities of LC-MS/MS to study the complex molecular interactions in the skin., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Complex regional pain syndrome (CRPS) is characterised by autonomic, sensory, and motor disturbances. The underlying mechanisms of the autonomic changes in CPRS are unknown. However, it has been postulated that sympathetic inhibition in the acute phase with locally reduced levels of noradrenaline is followed by an up-regulation of alpha-adrenoceptors in chronic CRPS leading to denervation supersensitivity to catecholamines. This exploratory study examined the effect of cutaneous sympathetic activation and inhibition on cutaneous noradrenaline release, vascular reactivity, and pain in CRPS patients and in healthy volunteers. Seven patients and nine controls completed whole-body cooling (sympathetic activation) and heating (sympathetic inhibition) induced by a whole-body thermal suit with simultaneous measurement of the skin temperature, skin blood flow, and release of dermal noradrenaline. CRPS pain and the perceived skin temperature were measured every 5 min during thermal exposure, while noradrenaline was determined from cutaneous microdialysate collected every 20 min throughout the study period. Cooling induced peripheral sympathetic activation in patients and controls with significant increases in dermal noradrenaline, vasoconstriction, and reduction in skin temperature. The main findings were that the noradrenaline response did not differ between patients and controls or between the CRPS hand and the contralateral unaffected hand, suggesting that the evoked noradrenaline release from the cutaneous sympathetic postganglionic fibres is preserved in chronic CRPS patients., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: To investigate the added value of myocardial perfusion scintigraphy imaging (MPI) in consecutive patients with suspected coronary artery disease (CAD) and a recent, normal exercise electrocardiography (ECG)., Methods: This study was a retrospective analysis of consecutive patients referred for MPI during a 2-year period from 2006-2007 at one clinic. All eligible patients were suspected of suffering from CAD, and had performed a satisfactory bicycle exercise test (i.e., peak heart rate > 85% of the expected, age-predicted maximum) within 6 mo of referral, their exercise ECG was had no signs of ischemia, there was no exercise-limiting angina, and no cardiac events occurred between the exercise test and referral. The patients subsequently underwent a standard 2-d, stress-rest exercise MPI. Ischemia was defined based on visual scoring supported by quantitative segmental analysis (i.e., sum of stress score > 3). The results of cardiac catheterization were analyzed, and clinical follow up was performed by review of electronic medical files., Results: A total of 56 patients fulfilled the eligibility criteria. Most patients had a low or intermediate ATPIII pre-test risk of CAD (6 patients had a high pre-test risk). The referral exercise test showed a mean Duke score of 5 (range: 2 to 11), which translated to a low post-exercise risk in 66% and intermediate risk in 34%. A total of seven patients were reported with ischemia by MPI. Three of these patients had high ATPIII pre-test risk scores. Six of these seven patients underwent cardiac catheterization, which showed significant stenosis in one patient with a high pre-test risk of CAD, and indeterminate lesions in three patients (two of whom had high pre-test risk scores). With MPI as a gate keeper for catheterization, no significant, epicardial stenosis was observed in any of the 50 patients (0%, 95% confidence interval 0.0 to 7.1) with low to intermediate pre-test risk of CAD and a negative exercise test. No cardiac events occurred in any patients within a median follow up period of > 1200 d., Conclusion: The added diagnostic value of MPI in patients with low or intermediate risk of CAD and a recent, normal exercise test is marginal.

Bone-seeking radionuclides, such as Sr-89, Sm-153, and Re-186, have been shown to have an effect on pain from bone metastasis in prostate cancer. The effect on bone pain in other cancer types, including breast cancer, remains unclear. The purpose of the study was to perform a systematic review of the use of radioisotopes for pain relief in metastatic breast cancer. A literature search was performed in PubMed, EMBASE, and Web of Science (1970 to September 2009) for clinical studies with a primary outcome of pain, performance status, or quality of life. Eligibility criteria were the following: (1) the trial must include at least 10 breast cancer patients with painful bone metastasis, (2) the radionuclide has been approved by regulatory authorities in Europe or the United States and is commercially available (Sr-89, Sm-153, and Re-186), (3) the dose of radionuclides must be clinically effective, (4) the primary endpoint must be pain, performance status or quality of life, and (5) separate reporting of efficacy should be available for breast cancer patients provided the trial included patients with various types of cancer. The literature search identified 189 individual studies of which 19 trials fulfilled the eligibility criteria. There were three randomized controlled trials of which two trials compared two different radionuclides, and one trial compared two doses of Sm-153. In addition, there were 16 uncontrolled trials. Reporting of trial research methodology in the randomized as well as the uncontrolled trials was low (median Jadad score of 1, range 1-2). Key trial details, such as patient recruitment, description of prior palliative therapies, baseline characteristics, follow up, and reporting of outcome was insufficient in a large proportion of the trials. According to Center of Evidence-based Medicine criteria, there is level 4 documentation for the effect of radionuclides in painful bone metastasis in breast cancer. It has been concluded that there is limited clinical evidence supporting the clinical effect of radionuclides in relieving pain from bone metastasis in breast cancer. Large, randomized controlled trials are needed to establish the utility of bone-seeking radionuclides in the palliative care of breast cancer patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: As we found no recent published reports on the amount and kind of research published from Danish hospitals without university affiliation, we have found it relevant to conduct a bibliometric survey disclosing these research activities., Material and Methods: We retrieved all scientific papers published in the period 2000-2009 emanating from all seven Danish non-university hospitals in two regions, comprising 1.8 million inhabitants, and which were registered in a minimum of one of the three databases: PubMed MEDLINE, Thomson Reuters Web of Science and Elsevier's Scopus., Results: In 878 of 1,252 papers, the first and/or last author was affiliated to a non-university hospital. Original papers made up 69% of these publications versus 86% of publications with university affiliation on first or last place. Case reports and reviews most frequently had authors from regional hospitals as first and/or last authors. The total number of publications from regional hospitals increased by 48% over the 10-year period. Publications were cited more often if the first or last author was from a university hospital and even more so if they were affiliated to foreign institutions. Cardiology, gynaecology and obstetrics, and environmental medicine were the three specialities with the largest number of regional hospital publications., Conclusion: A substantial number of scientific publications originate from non-university hospitals. Almost two thirds of the publications were original research published in international journals. Variations between specialities may reflect local conditions., Funding: not relevant., Trial Registration: not relevant.

Purpose: Being biodegradable, magnesium is considered a promising future implant material but very little is known about the biocompatibility for the tissues in direct contact with it. In this study, the degradation of pure magnesium implants in the skin of an isolated bovine udder was examined over a period of five hours., Methods: Microdialysis technique was used in order to investigate the reactions at the interface of implant and tissue. Pure titanium implants served as control. Degradation behavior and biocompatibility were evaluated via extracellular magnesium ion concentration and PGE2 and TNF alpha served as indicators of inflammation., Results: Concentrations of 5.5 mmol/l Mg2+ were detected at the beginning, which decreased to a plateau of about 3.5 mmol/l after approximately two and a half hours. PGE2 and TNF alpha concentrations indicated no major inflammatory tissue response to the degradation., Conclusions: These results give an idea of the ion burden at the implantation site of degrading magnesium and suggest good biocompatibility even at the tissue-implant interface.

Tissue viability imaging (TIVI) is a novel polarization spectroscopy method for assessing dermal vascular viability. The purpose of the present study was to compare TIVI with laser Doppler flowmetry (LDF) for assessment of pharmacologically induced vasodilation and vasoconstriction in human skin. Eight individual skin sites on the backs of seven healthy volunteers were randomized to receive an intradermal injection of prostaglandin E2 (PGE2, 10(-6) to 10(-9)M), norepinephrine (NE, 10(-5) to 10(-7)M), or vehicle. Vascular responses were measured by TIVI and LDF at the injection sites at 1-min intervals starting 2min before and ending 15min after the skin challenge. TIVI and LDF demonstrated significant dose-dependent and time-related vasodilator responses to PGE2 and vasoconstrictor responses to NE, respectively (p<0.001). The time course and dose-response functions for LDF and TIVI showed notable differences. Dose-response data showed a significant reduction in TIVI signal with NE 10-7M (10(-6) NE with LDF) whereas PGE2 10(-6)M was required to elicit a significant increase in TIVI signal (10(-8)M PGE2 with LDF). TIVI demonstrated relative vascular response changes of 0.79 to 1.63 of baseline values at 15min with NE 10(-5)M or PGE2 10(-6)M compared to values of 0.59 to 8.38 with LDF. There was a modest though significant correlation between relative changes in vascular responses measured by the two methods (p<0.0001, r(2)=0.521). A Bland-Altman difference plot demonstrated significant underestimation of relative increase versus baseline measured by TIVI (r(2)=0.99, p<0.0001). We conclude that TIVI polarization spectroscopy is a sensitive method for measurement of NE-induced vascular responses but that it is less sensitive than LDF for measurement of the PGE2-induced reactions., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Introduction: Painful bone metastases are common in advanced prostate cancer. We report the clinical outcome after administration of Samarium-153 ((153)Sm), an emitter of beta-particles that concentrates in the areas of enhanced osteoblastic activity., Methods: Twenty-two patients (median age 73 years) with metastatic, hormone-refractory prostate cancer received a single bolus infusion of (153)Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region, and most had inadequate pain relief to narcotic analgesics. Bone specific pain, analgesic score according to WHO, ECOG performance status, and blood count were evaluated before and up to 28 weeks after treatment., Results: Median follow-up was six weeks (mean 14 weeks). Eleven patients died within the 28 week observation period (ten from terminal disease), and four patients had their observation period truncated. Median pain score was 56.3%, 50.0%, and 50.0% of baseline values at week 4 (n = 20), 16 (n = 10), and 28 (n = 7), respectively. A reduction of baseline pain score by 50% or more was observed in 50%, 70% and 71% of patients at week 4, 16, and 28, respectively. Hematological toxicity was mild and reversible in most cases., Conclusion: Administration of (153)Sm to prostate cancer patients with painful bone metastases offered clinical relevant pain relief with tolerable hematological toxicity.

Cancer patients in general have a high risk of venous thromboembolic events (VTE) driven not only by patient-related risk factors, but also risk factors related to the disease and anti-cancer therapies. Cancer patients with documented VTE have a notably worse outcome than non-cancer VTE patients. Since VTE is a highly preventable condition, it is striking that large surveys have shown significant underuse of VTE prophylaxis in surgical cancer patients and in medical cancer patients in particular. Recently, guidelines have been issued from European and American medical oncology societies and organizations for identification of cancer patients at risk, and the guidelines give recommendations for treatment of individual groups of cancer patients. This review summarizes the recommendations for VTE prophylaxis and treatment from the recent guidelines and reviews some outstanding issues in VTE prophylaxis and treatment of cancer patients.

Background: Animal models have shown histamine to be released from the skin during the acute phase of a burn injury. The role of histamine during the early phase of thermal injuries in humans remains unclear., Purpose: The objectives of this trial were to study histamine release in human skin during the acute phase of a standardized thermal injury in healthy volunteers., Methods: Histamine concentrations in human skin were measured by skin microdialysis technique. Microdialysis fibers were inserted into the dermis in the lower leg in male healthy volunteers. A standardized superficial thermal injury was elicited by a heating thermode (49 degrees C) applied to the skin for 5 min. Histamine in dialysate was analyzed for up to 2 h after the injury using two different analytical methods., Results: Spectrofluorometric assay of histamine showed no histamine release in separate studies using 2-min samples over 20 min (n = 6) and 5-10-min samples over 120 min (n = 8). The histamine values were at the limits of the quantification limit of the spectrofluorometric assay. Confirmatory studies using a sensitive radioimmunoassay confirmed no histamine release within the first hour of a thermal injury (baseline 11.6 +/- 1.8 nM vs. post-burn values of 14.8 +/- 1.8 nM, n = 8)., Conclusions: Histamine is not released in human skin during the acute phase of a thermal injury.

Background: Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown., Materials and Methods: In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion., Results: Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers., Conclusions: Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.