bluuebunny/crossref_metadata_2025_split huggingface dataset:
NT‐proBNP in unstable coronary artery disease—experiences from the FAST, GUSTO IV and FRISC II trials
Authors: Jernberg Tomas , James Stefan , Lindahl Bertil , Stridsberg Mats , Venge Per , Wallentin Lars 
Published: February 2004

AbstractBackground:Risk stratification is important in patients with unstable coronary artery disease (CAD), i.e. unstable angina or non‐ST‐elevation myocardial infarction. This article focuses on the emerging role of N‐terminal pro brain natriuretic peptide (NT‐proBNP) and the results from the FAST, GUSTO IV and FRISC II trials.Methods:In the FAST study, NT‐proBNP was measured on admission in 755 patients admitted because of symptoms suggestive of unstable CAD. Follow up was performed after 40 months. The GUSTO IV and the FRISC II‐trials included patients with unstable CAD and NT‐proBNP was analyzed in 6806 and 2019 patients, with follow up after 1 and 2 years, respectively.Results:In the FAST study, patients in the 2nd, 3rd, and 4th NT‐proBNP quartile had a relative risk of subsequent death of 4.2 (1.6–11.1), 10.7 (4.2–26.8) and 26.6 (10.8–65.5), respectively. In the GUSTO IV trial, increasing quartiles of NT‐proBNP were related to short and long term mortality which at 1 year was; 1.8%, 3.9%, 7.7% and 19.2% (P<0.001), respectively. In multivariable analyses including well‐known predictors of outcome, NT‐proBNP level was independently associated to mortality in all three studies. In the FRISC II trial, the NT‐proBNP level, especially if combined with a marker of inflammation, identified those with the greatest benefit from an early invasive strategy.Conclusion:NT‐proBNP is strongly associated with mortality in patients with suspected or confirmed unstable CAD and, combined with a marker of inflammation, seems helpful in identifying those with greatest benefit from an early invasive strategy.
NT‐proBNP and BNP: biomarkers for heart failure management
Authors: Bettencourt Paulo 
Published: February 2004

AbstractGuidelines for the pharmacological treatment of heart failure (HF) are based on results from large clinical trials demonstrating benefit. State of the art pharmacological management of HF assumes that target doses should be the same as those used in trials. Thus equal doses are recommended for all in practical guidelines, but this strategy might not fit individual needs. NT‐proBNP and BNP emerged as potential biomarkers of clinical interest in HF management. NT‐proBNP and BNP are related to HF severity and to clinical status. NT‐proBNP and BNP are strongly associated with prognosis across the whole spectrum of HF patients. A pilot study has shown that NT‐proBNP‐guided therapy is associated with improved outcome in HF. Although at present there are still few data to make firm recommendations on the use of NT‐proBNP or BNP levels as biomarkers for HF management, future studies will provide further insight on this issue.
NT‐proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT‐proBNP substudy
Authors: Hartmann Franz , Packer Milton , Coats Andrew J.S. , Fowler Michael B. , Krum Henry , Mohacsi Paul , Rouleau Jean L. , Tendera Michal , Castaigne Alain , Trawinski Jürgen , Amann‐Zalan Ildiko , Hoersch Silke , Katus Hugo A. 
Published: February 2004

AbstractBackground:Neither profiles nor prognostic value of cardiac N‐terminal proBNP (NT‐proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo.Methods:Baseline and follow‐up plasma concentrations of NT‐proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol.Results:NT‐proBNP concentrations were increased at baseline (mean±S.D.=579±822 pmol/l, median=322.5 pmol/l) with a marked decrease during follow‐up in the carvedilol, but not in the placebo group. One‐year mortality rates were 3.9, 12 and 27.9% in the lower, middle and upper tertiles of NT‐proBNP, respectively. When mortality was calculated separately in the placebo and carvedilol group, rates were 0.8, 6.3 and 19.1% in the carvedilol treated but 6.7, 17.9 and 36.9% in the placebo treated patients.Conclusions:NT‐proBNP was a powerful predictor of subsequent all‐cause mortality in patients with severe CHF. This marker should therefore be further evaluated for risk stratification and monitoring of therapy in CHF.
NT‐proBNP and the diagnosis of heart failure: a pooled analysis of three European epidemiological studies
Authors: McDonagh T.A. , Holmer S. , Raymond I. , Luchner A. , Hildebrant P. , Dargie H.J. 
Published: February 2004

AbstractMany studies have shown that the B‐type natriuretic peptides (BNP and NT‐proBNP) are proven diagnostic markers for heart failure due to left ventricular systolic dysfunction. The manner in which they are to be used is still being unravelled; most single centre studies have chosen the best concentration of the peptide on ROC analysis as their cut‐point resulting in numerous different values for both BNP and NT‐proBNP appearing in the literature. We report a different approach of defining an age and sex corrected abnormal concentration for NT‐proBNP, derived from normal individuals within a large sample of 3051 subjects pooled from three European epidemiology studies and applying that to the entire population to detect HF and LVD. Three thousand and fifty one subjects were studied. Of these 10% (305) had significant LVD and 3.1% (94) had HF. The median concentrations of NT‐proBNP (IQR) in normals, those with LVD and in heart failure subjects were 20 pg/ml (10.30), 117.3 pg/ml (28.145) and 269.6 pg/ml (54.323), P<0.001, respectively. The area under the ROC curve for NT‐proBNP for the detection of ‘heart failure’ was 0.85 and 0.69 for LVD. NT‐proBNP was an independent predictor of the presence of HF on multivariate analysis. An abnormal NT‐proBNP was defined as being >95th centile for normals, age and sex corrected, and diagnosed HF with a sensitivity of 75% and a negative predictive value of 99%. In an additional analysis in a breathless subgroup of our population, in 30% a raised NT‐proBNP concentration could be explained by HF due to LVD, in another 64% the high BNP level was associated with some other structural of functional cardiac abnormality or renal impairment. We were unable to assign a possible cause to the high NT‐proBNP values in 5.9% of this breathless subgroup of the population. An abnormal NT‐proBNP concentration is an accurate diagnostic test both for the exclusion of HF in the population and in ruling out LVD in breathless subjects. An elevated NT‐proBNP merely indicates the presence of ‘cardio‐renal distress’ and should prompt referral for further investigation.
Analytical performance of the N terminal pro B type natriuretic peptide (NT‐proBNP) assay on the Elecsys™ 1010 and 2010 analysers
Authors: Collinson P.O. , Barnes S.C. , Gaze D.C. , Galasko G. , Lahiri A. , Senior R. 
Published: February 2004

AbstractThe Elecsys NT‐proBNP assay is based on two polyclonal antibodies directed at residues 1–21 and 39–50 of the NT‐proBNP molecule. Analytical performance was assessed using NCCLS protocol EP‐5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7–1.6 (1010) and 1.2–1.5 (2010) and between run CV 5.3–6.7 (1010) and 4.4–5.0 (2010). In the multicentre evaluation within run CV was 1.0–2.5% with total imprecision 1.5–2.5% and between labs imprecision 3.8–4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x−0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 °C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT‐proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT‐proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT‐proBNP values increased with age and were higher in women than men.
Pressure pain thresholds of tender point sites in patients with fibromyalgia and in healthy controls
Authors: Maquet Didier , Croisier Jean‐Louis , Demoulin Christophe , Crielaard Jean‐Michel 
Published: February 2004

AbstractPressure pain threshold (PPT) is defined as the minimum force applied which induces pain. This measure has proven to be commonly useful in evaluating tenderness symptom. Our aim was to study the intra‐examiner reproducibility of PPT measurement, define cutoffs in normal groups, and compare these results with patients with fibromyalgia (FM). Fifty healthy females, 50 healthy males, and 20 patients with FM participated in the study. PPTs were assessed for 18 specific tender point sites by a dolorimeter. The intra‐individual coefficient of variation determined by a test—retestPPT measurement procedure with 3‐days interval reached, respectively, 17% and 13% in healthy females and males, versus 24% in patients with FM. PPTs were significantly lower in healthy females than in healthy males (p<0.01). Statistical analysis failed to show any differences between the dominant and nondominant side for both normal groups. PPTs were lower over all examined areas in patients with FM than those obtained in healthy females (p<0.000). Lower cutoff levels were calculated from normal values for all specific tender point sites. On average, 14 tender point sites in patients with FM were under the established lower cutoffs. In conclusion, pressure pain sensitivity was influenced by the anatomical localization of tender point and gender differences. Lowest PPTs were localized in trapezius, occiput, anterior cervical, and second rib. The reduction of total tender point score in patients with FM averaged 60% comparatively with normal values. PPT reproducibility and discrimination between the two groups were optimal for the gluteal and knee sites.
No analgesic effect of ibuprofen or paracetamol vs placebo for hysterectomies
Authors: Dahl V. , Ernø P.E. , Ræder J.C. 
Published: February 2004

The aim of the present study was to evaluate the postoperative opioid‐sparing effect of a pre‐operative nonsteroidal anti‐inflammatory drug (NSAID) (ibuprofen) vs paracetamol in a prospective, double‐blind, placebo‐controlled study. It was also investigated whether the use of ibuprofen or paracetamol would influence the amount of surgical bleeding.Sixty‐six women scheduled for elective open hysterectomy were randomized into one of three groups. All patients received premeditation (diazepam 10 mg) and test drugs orally 1 h before the start of anaesthesia: Group 1 (n = 23) received 800 mg ibuprofen; Group 2 (n = 22) received 1000 mg paracetamol; and Group 3 (n = 21) received placebo. General anaesthesia was given with thiopentone‐fentanyl‐atracurium induction, and maintained with nitrous oxide‐isoflurane. Postoperatively, the patients were evaluated hourly during the recovery period, and 1 and 4 days after the procedure.Postoperative pain was measured by visual analogue scale (VAS), verbal pain score and the need of standardized opioid rescue medication. Intra‐operative bleeding was measured, as well as reduction in blood haemoglobin content 24 h and 4 days after the procedure.No differences were found between the groups in postoperative pain measured by any variable or opioid consumption at any time. The amount of surgical bleeding was equal in the three groups.Ibuprofen or paracetamol given pre‐operatively to hysterectomy patients do not have a postoperative analgesic or opioid‐sparing effect. Perioperative surgical bleeding is not influenced by these drugs.
GABA‐receptor control of the amplitude and duration of the neuronal responses to formalin in the rat spinal cord
Authors: Green G.M. , Dickenson A. 
Published: February 2004

The GABAergic inhibitory system in the dorsal horn of the spinal cord has been implicated in the modulation of pain, including the control of nociceptive transmission during inflammation. This electrophysiological study examined the effects of the GABAA and GABAB receptor antagonists, bicuculline and CGP35348, on the magnitude and duration of the formalin response. The responses of spinal nociceptive dorsal horn neurones to subcutaneous injection of formalin into the hindpaw in the anaesthetized rat were recorded. Both phases of the formalin response were monitored, and the antagonists were administered either simultaneously with formalin or 50 min after injection of formalin.Bicuculline (50 μg), the GABAA antagonist, administered simultaneously with formalin significantly increased the magnitude of the overall response, especially the second phase, and also abolished the silent interphase period. In addition, 50 min after injection of formalin, bicuculline increased the duration of the second phase in a dose‐dependent manner. CGP35348 (250 μg), the GABAB antagonist, administered 50 min after injection of formalin also increased the duration of the second phase significantly, but had no effect on the magnitude of the response or the silent interphase when administered simultaneously with formalin.These results show that GABAA‐ and GABAB‐receptor‐mediated inhibitions are involved in controlling the duration of the second phase of the formalin response, and that GABAA‐receptor‐mediated inhibition also contributes to the manifestation of the silent interphase period and the magnitude of the second phase. Thus, GABA neurones are critical in determining the level and duration of nociceptive information transmitted through the spinal cord during inflammation.
Lesions of the caudal ventrolateral medulla block the hypertension‐induced inhibition of noxious‐evoked c‐fos expression in the rat spinal cord
Authors: Tavares I. , Almeida A. , Albino‐Teixeira A. , Lima D. 
Published: February 2004

The effect of lesioning the lateral portion of the caudal ventrolateral medullary reticular formation (VLMIat) on the noxious‐evoked expression of the c‐fos proto‐oncogene in spinal neurons, was studied in short‐term hypertensive rats. Occlusion of the renal artery for 96 h in unlesioned animals induced a 52% increase in blood pressure (BP) and a 66% decrease in the number of Fos‐immunoreactive (Fos‐IR) spinal cells following noxious cutaneous stimulation, as compared to values in normotensive controls. Lesioning the VLMIat in hypertensive rats by unilateral quinolinic acid (QA) injection (0.3 μl of a 180 nmol/μl solution) 24 h before noxious stimulation, prevented the Fos‐IR cell decrease. In normotensive rats, lesioning the VLMIat produced no changes in c‐fos expression. To investigate the role played by the VLMIat in cardiovascular control, BP and heart rate (HR) were measured during local injections of QA or glutamate (0.5 μl of a 100 nmol/μl solution) to normotensive animals. Injections of QA produced an immediate rise in BP and HR which reached maximal values (18 and 14% increase, respectively) 5 min after the administration onset, then returning gradually to baseline levels. Glutamate injections resulted in an immediate decrease of the same values, which reached 29 and 39%, respectively, 4 min after the beginning of injection, after which they decreased to baseline levels.These results suggest that VLMIat neurons inhibit nociceptive spinal neurons in response to rises in blood pressure, while exerting negative control of cardiovascular parameters. It is suggested that the VLMIat is involved in the genesis of hypoalgesia during hypertension.
Sensory manifestations in experimental and work‐related chronic neck‐shoulder pain
Authors: Madeleine P. , Lundager B. , Voigt M. , Arendt‐Nielsen L. 
Published: February 2004

Little is known about the mechanisms leading to chronic neck‐shoulder musculo‐skeletal disorders. The aim of the present study was to investigate and compare the sensory manifestations of experimental or chronic neck‐shoulder pain under controlled, low load, repetitive work.Experimental and clinical experiments were carried out. In Experiment 1, experimental muscle pain was induced in healthy subjects by intramuscular injection of hypertonic saline in the trapezius (n=10) and infraspinatus (n=10) muscles. Experiment 2 was performed on 18 workers with (n= 12) and without (n= 6) chronic neck‐shoulder pain. Sensory assessments were performed before and/or after a session of controlled, low load, repetitive work. The pain intensity was assessed by a visual analogue scale. The pain quality and location(s) were monitored together with pressure‐pain thresholds.Moderate‐to‐strong deep pain intensity was experienced in the experimental and clinical part of the working session (six patients out of 12). The verbal descriptors used to describe the experimental or chronic pain qualities were partially similar, i.e. first of all verbal descriptors from the sensory class. The patterns of local and referred pain characteristics were similar (around the shoulder girdle), but it is difficult to evoke pain in extensive areas with hypertonic saline. Patients exhibited hypersensitivity or tenderness to pressure stimuli in both sides of the upper body, i.e. in the trapezius, supraspinatus, infraspinatus and pectoralis major muscles (p<0.05). This hypersensitivity was only seen at the referred pain site in the healthy volunteers exposed to infraspinatus experimental muscle pain.In conclusion, the present study demonstrated similar sensory manifestations in the experimental and clinical neck‐shoulder pain experiments. The presented experimental model can most likely be used to investigate the underlying pain mechanisms involved in work‐related chronic musculoskeletal pain.
Oral ibuprofen and diclofenac in post‐operative pain: A quantitative systematic review
Authors: Collins Sally L. , Moore R. Andrew , McQuay Henry J. , Wiffen Philip J. 
Published: February 2004

Surveys show consistently that pain is not treated well. Improvement depends on knowing which treatments are the most effective. We used systematic review to compare the relative efficacy of two common analgesics, ibuprofen and diclofenac, in post‐operative pain.Studies were identified by searching MEDLINE (1966 to Dec 1996), EMBASE (1980 to Jan 1997), the Cochrane Library (Aug 1996), Biological Abstracts (Jan 1985 to Dec 1996) and the Oxford Pain Relief Database (1950 to 1994). We sought randomised, controlled, single‐dose comparisons of oral ibuprofen or diclofenac against placebo. Summed pain relief or pain intensity difference over 4–6 h was extracted and converted into dishotomous information yielding the number of patients with at least 50% pain relief. This was then used to calculate the relative benefit and the number‐needed‐to‐treat for one patient to achieve at least 50% pain relief.Thirty‐four reports compared ibuprofen and placebo (3591 patients), six compared diclofenac with placebo (840 patients), and there were two direct comparisons of diclofenac 50 mg and ibuprofen 400 mg (130 patients). In post‐operative pain, the numbers‐needed‐to‐treat for ibuprofen 200 mg were 3.3 (95% confidence interval 2.8–4.0) compared with placebo, for ibuprofen 400 mg 2.7 (2.5–3.0), for ibuprofen 600 mg 2.4 (1.9–3.3), for diclofenac 50 mg 2.3 (2.0–2.7) and for diclofenac 100 mg 1.8 (1.5–2.1). Direct comparisons of diclofenac 50 mg with ibuprofen 400 mg showed no significant difference between the two.Both drugs worked well. Choosing between them is an issue of dose, safety and cost.
Systemic local‐anaesthetic‐type drugs in chronic pain: A systematic review
Authors: Kalso E. , Tramèr M.R. , McQuay H.J. , Moore R.A. 
Published: February 2004

Basic research indicates that systemic local‐anaesthetic‐type drugs that block sodium channels are effective in pain due to nerve damage. These drugs were first used as analgesics in the 1950s and they are still commonly used to try to relieve neuropathic pain and incident pain caused by cancer. As they are potentially toxic, these drugs should not be used without proven effectiveness. For these reasons, a systematic review of randomized controlled trials of systemically administered local‐anaesthetic‐type drugs in chronic pain was performed. Main outcomes were pain relief or pain intensity difference and adverse effects. Twenty‐one reports were found, and four publications were excluded. In the remaining 17 studies (450 patients), 10 used intravenous lignocaine, two used intranasal lignocaine, four used oral mexiletine and one used oral tocainide.The best documented effective dose of intravenous lignocaine was 5 mg/kg, and when infused over 30 min it was well tolerated. Intravenous lignocaine was effective in all four studies in non‐cancer‐related neuropathic pain. In migraine, lignocaine produced an inconsistent effect. Lignocaine was without effect in all three studies in cancer‐related pain.Oral mexiletine showed some efficacy in all three studies in pain due to peripheral nerve damage, but lacked effect in the only study in central pain. Only minor dose‐related adverse effects were reported in the 85 patients given mexiletine 225–750 mg.Local‐anaesthetic‐type drugs are effective in pain due to nerve damage, but there is little or no evidence to support their use in cancer‐related pain.
Transdermal fentanyl for pain control in adults with chronic cancer pain
Authors: Kongsgaard U.E. , Poulain P. 
Published: February 2004

The transdermal therapeutic system (TTS) for fentanyl is a drug‐delivery system for use in patients with chronic pain who require an opioid analgesic. A multicentre, randomized, double‐blind, placebo‐controlled study was performed to evaluate the efficacy and safety of TTS‐fentanyl as an analgesic for chronic cancer pain. One hundred and thirty‐eight patients entered a 15‐day dose‐titration period, followed by a 9‐day double‐blind period (95 patients) with TTS‐fentanyl or placebo. Fifty‐five patients entered a follow‐up period of indefinite duration. For the majority of patients, TTS‐fentanyl 50–75 μg/h provided effective analgesia. Due to an unexpectedly high placebo response, it was not possible to show fentanyl to be statistically superior to placebo at the 5% significance level. Nine patients treated with fentanyl and 13 treated with placebo were withdrawn from the study during the double‐blind therapy because of insufficient efficacy (not significant), while 66% of fentanyl‐treated patients experienced effective pain control compared with 48% of placebo‐treated patients (p = 0.071). During the course of the double‐blind therapy, the mean dose of rescue morphine increased slightly more in the placebo group than in the fentanyl group. At the end of the double‐blind phase, the investigators rated trial medication as being ‘good'; or ‘excellent'; in 30 patients in the fentanyl group and 23 in the placebo group. TTS‐fentanyl appeared to be well tolerated, with a low incidence of constipation, somnolence and nausea.Due to an unexpectedly high placebo response it was not possible to demonstrate fentanyl to be statistically superior to placebo. This may reflect the practical difficulties of performing clinical trials in cancer patients with great inter‐individual variability.