Increased serum levels of β₂-GPI-Lp(a) complexes and their association with premature atherosclerosis in patients with rheumatoid arthritis

BackgroundOur recent study found the existence of complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a)[Lp(a)] in circulation and the complex concentrations were increased in sera of systemic lupus erythematosus patients. The concentration of β₂-GPI-Lp(a) and its relationship with premature atherosclerosis were evaluated in rheumatoid arthritis (RA) patients.MethodsSerum concentrations of β₂-GPI-Lp(a) were measured in 53 active RA patients and 40 healthy controls by a “sandwich” ELISA. β₂-GPI-ox-LDL, ox-Lp(a), ox-LDL and anti-β₂-GPI were also measured by ELISAs. In addition, inflammatory markers were examined.ResultsSerum β₂-GPI-Lp(a) (1.12 ± 0.25 U/ml vs. 0.87 ± 0.19 U/ml, P < 0.0001) and β₂-GPI-ox-LDL (1.01 ± 0.20 U/ml vs. 0.80 ± 0.08 U/ml, P < 0.0001) concentrations in RA were both significantly higher than those of controls. Ox-Lp(a) (8.38 ± 6.69 mg/l vs. 5.49 ± 4.31 mg/l, P < 0.05) and ox-LDL (0.68 ± 0.65 mg/l vs. 0.37 ± 0.13 mg/l, P = 0.001) were also higher in RA than in controls. The area under the ROC curve (AUC) for β₂-GPI-Lp(a) (0.787) was larger than for ox-Lp(a) (0.731). AUC of β₂-GPI-ox-LDL (0.858) was also larger than for ox-LDL (0.785). β₂-GPI-Lp(a) and β₂-GPI-ox-LDL were positively correlated with ox-Lp(a), ox-LDL and CRP, respectively.Conclusionsβ₂-GPI-Lp(a) complex concentrations increased in active RA. Inflammation and oxidative stress in RA contribute to the increase of ox-Lp(a) and subsequently the formation of β₂-GPI-Lp(a).     

Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus

ObjectivesMatrix metalloproteinases (MMPs) are suggested to play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study is to examine the MMPs expressions and activities in Taiwanese RA and SLE patients.Design and methodsLevels and activities of plasma MMP-2 and MMP-9 were investigated by enzyme-linked immunosorbent assay and zymography, respectively.ResultsMMP-2 levels in control subjects, RA and SLE patients were 146.1 ± 34.2, 194.0 ± 24.2 and 208.9 ± 75.9 ng/mL respectively, and for MMP-9 were 51.4 ± 57.1, 567.7 ± 313.1 and 208.7 ± 105.5 ng/mL respectively. Both MMP-2 and MMP-9 levels and activities from all patients were significantly higher than that from control subjects.ConclusionsMMP-2 levels in both patients groups were approximately 1.3–1.4 folds higher than that in control subjects, notably, MMP-9 levels were 11- and 4-folds significantly higher, respectively, in RA and SLE patients. The results which MMP-2 and MMP-9 levels and activities are significantly elevated support the involvement of MMPs proteins in these autoimmune disorders.     

The acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock

IntroductionFluid resuscitation therapy is the initial step of treatment for hemorrhagic shock. In the present study we aimed to investigate the acute effects of acetate-balanced colloid and crystalloid resuscitation on renal oxygenation in a rat model of hemorrhagic shock. We hypothesized that acetate-balanced solutions would be superior in correcting impaired renal perfusion and oxygenation after severe hemorrhage compared to unbalanced solutions.MethodsIn anesthetized, mechanically ventilated rats, hemorrhagic shock was induced by withdrawing blood from the femoral artery until mean arterial pressure (MAP) was reduced to 30 mmHg. One hour later, animals were resuscitated with either hydroxyethyl starch (HES, 130/0.42 kDa) dissolved in saline (HES-NaCl; n = 6) or a acetate-balanced Ringer's solution (HES-RA; n = 6), as well as with acetated Ringer's solution (RA; n = 6) or 0.9% NaCl alone (NaCl; n = 6) until a target MAP of 80 mmHg was reached. Oxygen tension in the renal cortex (CμPO₂), outer medulla (MμPO₂), and renal vein were measured using phosphorimetry.ResultsHemorrhagic shock (MAP = 30 mmHg) significantly decreased renal oxygenation and oxygen consumption. Restoring the MAP to 80 mmHg required 24.8 ± 1.7 ml of NaCl, 21.7 ± 1.4 ml of RA, 5.9 ± 0.5 ml of HES-NaCl (p < 0.05 vs. NaCl and RA), and 6.0 ± 0.4 ml of HES-RA (p < 0.05 vs. NaCl and RA). NaCl, RA, and HES-NaCl resuscitation led to hyperchloremic acidosis, while HES-RA resuscitation did not. Only HES-RA resuscitation could restore renal blood flow back to ～85% of baseline level (from 1.9 ± 0.1 ml/min during shock to 5.1 ml ± 0.2 ml/min 60 min after HES-RA resuscitation) which was associated with an improved renal oxygenation (CμPO₂ increased from 24 ± 2 mmHg during shock to 50 ± 2 mmHg 60 min after HES-RA resuscitation) albeit not to baseline level. At the end of the protocol, creatinine clearance was decreased in all groups with no differences between the different resuscitation groups.ConclusionWhile resuscitation with the NaCl and RA (crystalloid solutions) and the HES-NaCl (unbalanced colloid solution) led to hyperchloremic acidosis, resuscitation with the HES-RA (acetate-balanced colloid solution) did not. The HES-RA was furthermore the only fluid restoring renal blood flow back to ～85% of baseline level and most prominently improved renal microvascular oxygenation.     

Correlation of a multi-cytokine panel with clinical disease activity in patients with rheumatoid arthritis

ObjectiveExplore the potential use of a cytokine panel as biochemical markers of disease activity in rheumatoid arthritis (RA) patients.Design and methods57 adult RA patients were assessed using five validated clinical disease activity tools: Health Assessment Questionnaire (HAQ), standard 28-joint Disease Activity Score (DAS28), DAS28 using C-reactive protein (DAS28-CRP), Clinical Disease Activity Index (CDAI), and Simple Disease Activity Index (SDAI). Plasma cytokine levels (IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN-γ, TNF-α, IL1α, IL1β, MCP1, and EGF) were measured in 47 of the 57 patients and correlated with clinical indicators.ResultsWe found significant correlations between plasma levels of IL-6 and all clinical measures of disease activity; Spearman coefficients (p values) were: HAQ: 0.347(0.017); DAS28: 0.409(0.005); DAS-CRP: 0.378(0.011); CDAI: 0.312(0.033); SDAI: 0.310(0.039); ESR: 0.448(0.002); and CRP: 0.513(0.001). IFN-γ also correlated with DAS-CRP: 0.309(0.039) and SDAI: 0.301(0.044). Furthermore, the levels of IL-6 and IFN-γ increased significantly with worsening disease, as defined by the European League Against Rheumatism (EULAR) classification of disease activity.ConclusionA significant correlation between plasma levels of IL-6 and clinical disease activity in patients with RA suggests a future role of IL6 as a disease activity marker.     

Potential negative effects of epinephrine on carotid blood flow and ETCO2 during active compression-decompression CPR utilizing an impedance threshold device

ObjectivesThis study examines the effects of IV epinephrine administration on carotid blood flow (CBF) and end tidal CO₂ (ETCO₂) production in a swine model of active compression–decompression CPR with an impedance threshold device (ACD-CPR + ITD).MethodsSix female swine (32 ± 1 kg) were anesthetized, intubated and ventilated. Intracranial, thoracic aorta and right atrial pressures were measured via indwelling catheters. CBF was recorded. ETCO₂, SpO₂ and EKG were monitored. V-fib was induced and went untreated for 6 min. Three minutes each of standard CPR (STD), STD-CPR + impedance threshold device (ITD) and active compression–decompression (ACD)-CPR + ITD were performed. At minute 9 of the resuscitation, 40 μg/kg of IV Epinephrine was administered and ACD-CPR + ITD was continued for 1 min. Statistical analysis was performed with a paired t-test. p values of <0.05 were considered statistically significant and all values are reported in mmHg unless otherwise noted.ResultsAortic pressure, cerebral and coronary perfusion pressures increased from STD < STD + ITD < ACD-CPR + ITD (p <0.001). Epinepherine administered during ACD-CPR + ITD signficantly increased mean aortic pressure (29 ± 5 vs 42 ± 12, p = 0.01), cerebral perfusion pressure (12 ± 5 vs 22 ± 10, p = 0.01), and coronary perfusion pressure (8 ± 7 vs 17 ± 4, p = 0.02); however, mean CBF and ETCO₂ decreased (respectively 29 ± 15 vs 14 ± 7.0 ml/min, p = 0.03; 20 ± 7 vs 18 ± 6, p = 0.04).ConclusionsIn this model, administration of epinepherine during ACD-CPR + ITD signficantly increased markers of macrocirculation, while significantly decreasing carotid blood flow and ETCO₂. This calls into question the ability of calculated perfusion pressures to accurately reflect oxygen delivery to end organs. The administration of epinepherine during ACD-CPR + ITD does not improve cerebral tissue perfusion.     

Isolation and activation of human neutrophils in vitro. The importance of the anticoagulant used during blood collection

ObjectivesTo assess the effect of different anticoagulants (EDTA, citrate and heparin) on the isolation procedure of human neutrophils and in the subsequent alterations of calcium levels and respiratory burst induced by phorbol myristate acetate (PMA).Design and methodsIsolation of human neutrophils from whole blood was performed by the gradient density centrifugation method. PMA-induced neutrophil burst was measured by chemiluminescence. Intracellular calcium ([Ca²⁺]_i) was measured using Fluo-3 AM, a calcium-sensitive dye.ResultsEDTA provided the highest number of isolated neutrophils/mL of blood (1.7 × 10⁶ ± 1.5 × 10⁵) when compared with citrate (0.46 × 10⁶ ± 0.95 × 10⁵) and heparin (0.66 × 10⁶ ± 0.15 × 10⁵). EDTA originated less degree of PMA-induced activation (370 ± 30%) relatively to citrate (830 ± 98%) and heparin (827 ± 77%). [Ca²⁺]_i was lower with EDTA (122 ± 11 nM) when compared with citrate and heparin (150 ± 13 and 230 ± 30 nM).ConclusionThe anticoagulant used during blood collection interfered differently with the yield of isolated neutrophils as well as on their calcium levels and reactivity to PMA.     

A feasibility study evaluating the role of cerebral oximetry in predicting return of spontaneous circulation in cardiac arrest

To date there has been no reliable noninvasive real time monitoring available to determine cerebral perfusion during cardiac arrest.ObjectivesTo investigate the feasibility of using a commercially available cerebral oximeter during in-hospital cardiac arrest, and determine whether this parameter predicts return of spontaneous circulation (ROSC).MethodsCerebral oximetry was incorporated in cardiac arrest management in 19 in-hospital cardiac arrest cases, five of whom had ROSC. The primary outcome measure was the relationship between rSO₂ and ROSC.ResultsThe use of cerebral oximetry was found to be feasible during in hospital cardiac arrest and did not interfere with management. Patients with ROSC had a significantly higher overall mean ± SE rSO₂ (35 ± 5 vs. 18 ± 0.4, p < 0.001). The difference in mean rSO₂ between survivors and non-survivors was most pronounced in the final 5 min of cardiac arrest (48 ± 1 vs. 15 ± 0.2, p < 0.0001) and appeared to herald imminent ROSC. Although spending a significantly higher portion of time with an rSO₂ > 40% was found in survivors (p < 0.0001), patients with ROSC had an rSO₂ above 30% for >50% of the duration of cardiac arrest, whereas non-survivors had an rSO₂ that was below 30% > 50% of their cardiac arrest. Patients with ROSC also had a significantly higher change in rSO₂ from baseline compared to non-survivors (310% ± 60% vs. 150% ± 27%, p < 0.05).ConclusionCerebral oximetry may have a role in predicting ROSC and the optimization of cerebral perfusion during cardiac arrest.     

Comparative study on the pharmacodynamics of cisatracurium: continuous infusion or intermittent bolus injection

ObjectiveTo explore a better administration way through comparison of the pharmacodynamics of cisatracurium administered by continuous infusion or intermittent bolus injection.MethodsThirty patients (ASAI-II) who had no neuromuscular disease and underwent selective surgery under general anesthesia were randomly divided into group I and II (each group with 15 patients). In group I, patients received cisatracurium by continuous infusion and in group II, by intermittent bolus injection. The responses of adductor pollicis to train-of-four (TOF) stimulation were monitored. The duration of neuromuscular blockade, recovery index and total dose of cisatracurium consumption were recorded in the two groups. Intravenous anesthesia was used for anesthesia induction and sevoflurane inhalation for maintenance of anesthesia.ResultsThe mean infusion rate was significantly lower in group I (0.78 ± 0.15 μg.kg^? 1.min^? 1) than in group II (1.09 ± 0.33 μg.kg^? 1.min^? 1) (P < 0.05). There was no significant difference in duration of neuromuscular blockade between the two groups (P > 0.05). The recovery index was 13.13 ± 3.36 min in group I and 14.38 ± 4.48 min in group II, which indicated that the recovery was faster in group I than in group II, but without statistical significance (P > 0.05). During the duration of neuromuscular blockade, 8 patients had T₁ < 3%, 4 T₁ of 3%–7% and 3 T₁ of 7%–10% in group I; T₁ was maintained between 0 and 20% in group II.ConclusionsAlthough cisatracurium consumption was significantly lower in continuous infusion than in intermittent bolus injection, continuous infusion can obtain more stable neuromuscular blockade than intermittent bolus injection.     

Influence of diabetes on homocysteine-lowering therapy in chronic hemodialysis patients

IntroductionThe effect of homocysteine (Hcy)-lowering therapy may be different in hemodialysis (HD) patients with and without diabetes mellitus (DM).MethodsStable HD patients with uremia were administered folic acid and vitamin B for 3 months. The impact of treatment was compared in patients with and without DM.ResultsA total of 61 patients (31 men and 30 women) aged 56 ± 13 y completed the study. Among these, 44 patients (72%) did not have DM and 17 (28%) had DM. At baseline, total Hcy and high-sensitivity C-reactive protein (hsCRP) levels were similar. After treatment, the levels of total Hcy and hsCRP were significantly decreased in the nondiabetic group (total Hcy level decreased from 33.63 ± 14.13 μmol/l to 18.94 ± 8.46 μmol/l, p < 0.001; hsCRP level decreased from 0.58 mg/dl [range, 0.21–1.05 mg/dl] to 0.22 mg/dl [range, 0.11–0.53 mg/dl], p < 0.001) but not in the diabetic group (total Hcy level decreased from 34.97 ± 17.12 μmol/l to 29.53 ± 11.36 μmol/l, p = 0.057; hsCRP level decreased from 0.80 mg/dl [range, 0.24–1.47 mg/dl] to 0.49 mg/dl [range, 0.45–0.98 mg/dl], p = 0.28). Serial monitoring of total Hcy level showed a more sustained effect of therapy on patients without DM.ConclusionFolic acid and vitamin B administration significantly lower total Hcy and hsCRP levels in HD patients without DM but not in those with DM.     

Determination of sensitivity and specificity of a novel gene dosage assay for prenatal screening of trisomy 21 syndrome

ObjectiveTo compare the gene dosage results achieved by a novel multiplex quantitative assay with cytogenetic and quantitative fluorescent polymerase chain reaction (QF-PCR) analysis for prenatal screening of trisomy 21 syndrome on corresponding fetal samples.Design and methodsFetal samples (n = 134) were collected from pregnant women considered high risk for having trisomy 21 affected fetus. Cytogenetic analysis and QF-PCR were performed. Then, the relative gene dosage of DSCAM and DYRK1A2 genes was determined on corresponding samples using comparative delta cycle of threshold (ΔC_T) method.ResultsThe mean gene dosage ratio was 1.55 ± 0.11 (95% CI:1.51–1.58) in trisomy 21 cases and 1.01 ± 0.12 (95% CI:0.98–1.03) in normal samples (p value < 0.001). The results were in agreement to the results of cytogenetic and QF-PCR analysis with the overall specificity of 0.96 (95% CI:0.91–0.98) and the sensitivity of 0.80 (95% CI:0.49–0.94).ConclusionsThis gene dosage assay is appropriate for the screening of high risk pregnant women and is readily amenable to automation.     

Revaluation of biological variation of glycated hemoglobin (HbA(1c)) using an accurately designed protocol and an assay traceable to the IFCC reference system

BackgroundGlycated hemoglobin (HbA_1c) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA_1c biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol.MethodsWe took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at ? 80 °C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment.ResultsThe bias (mean ± SD) of the Roche immunoassay was 0.3% ± 0.7%, confirming the traceability of the employed assay. No difference was found in HbA_1c values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA_1c had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~ 10%.ConclusionsFor the first time we defined biological variation and derived indices for the clinical application of HbA_1c measurements using an accurately designed protocol and an assay standardized according to the IFCC.     

Long-term ursodeoxycholate improves circulating redox changes in primary biliary cirrhotic patients

Background and aimsCholestasis is associated with systemic and hepatic oxidative and nitrosative stress; in this scenario, the conjugated hydrophilic bile salt ursodeoxycholate (UDCA) might play a protective role.MethodsCirculating oxidative and nitrosative stress markers were assessed in patients with primary biliary cirrhosis (PBC) before and during UDCA (15–20 mg/kg/day) therapy.ResultsIn patients with stage I–II PBC, UDCA improved ALT and alkaline phosphatase levels and near normalized serum thioredoxin (1.97 ± 0.37 vs 2.41 ± 0.39 nmol/L), nitrotyrosine (15 ± 4 vs 22 ± 7 nmol/L), nitrosothiols (144 ± 28 vs 205 ± 84 nmol/L) and K-18 levels (162 ± 21 vs 228 ± 33 U/L). Conversely, less marked changes were noted in patients with stages III–IV who showed lower thioredoxin (1.01 ± 0.31 nmol/L), higher nitrosothiols (605 ± 64 nmol/L), nitrotyrosine (62 ± 13 nmol/L) and K-18 levels (521 ± 57 U/L). Overall, thioredoxin was inversely related with nitrotyrosine (r = ? 0.838, P < 0.001) and K-18 (r = ? 0.838, P < 0.001) levels. Nitrosothiols and K-18 were linearly and significantly related with nitrotyrosine (r = 0.862, P < 0.001; r = 0.894, P < 0.001, respectively).ConclusionsOxidative and nitrosative changes in patients with PBC are effectively counteracted by UDCA. The protective effect of UDCA, however, are limited to early disease stages and progressively diminishes with ongoing cholestasis.     

Reduced hands-off-time and time to first shock in CPR according to the ERC Guidelines 2005

Background and aimChest compressions and early defibrillation are crucial in cardiopulmonary resuscitation (CPR). The Guidelines 2005 brought major changes to the basic life support and automated external defibrillator (BLS–AED) algorithm. We compared the European Resuscitation Council's Guidelines 2000 (group ‘00) and 2005 (group ‘05) on hands-off-time (HOT) and time to first shock (TTFS) in an experimental model.MethodsIn a randomised, cross-over design, volunteers were assessed in performing BLS–AED over a period of 5 min on a manikin in a simulated ventricular fibrillation cardiac arrest situation. Ten minutes of standardised teaching and 10 min of training including corrective feedback were allocated for each of the guidelines before evaluation. HOT was chosen as the primary and TTFS as the secondary outcome parameter.ResultsForty participants were enrolled; one participant dropped out after group allocation. During the 5-min evaluation period of adult BLS–AED, HOT was significantly (p < 0.001) longer in group ‘00 [273 ± 3 s (mean ± standard error)] than in group ‘05 (188 ± 3 s). The TTFS was significantly (p < 0.001) longer in group ‘00 (91 ± 3 s) than in group ‘05 (71 ± 3 s).ConclusionIn this manikin setting, HOT and TTFS improved with BLS–AED performed according to Guidelines 2005.     

Clinical remission following treatment with tumour necrosis factor-alpha antagonists is not accompanied by changes in asymmetric dimethylarginine in patients with rheumatoid arthritis

ObjectivesRheumatoid arthritis (RA) is characterised by impaired endothelial function which contributes to increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and contributes to endothelial dysfunction. The aim of the present longitudinal study was to investigate the effects of tumour necrosis factor alpha (TNFα) antagonists on serum concentrations of ADMA in RA patients.Design and methodsThirty-five patients (age (mean ± SD) 55 ± 15 years, 21 women) who qualified for anti-TNFα therapy were included in the study. ADMA was measured by ELISA in all patients prior to starting anti-tumour necrosis factor alpha treatment, and 2 weeks and 3 months after initiation of treatment. Generalised estimating equations were used to analyse the change in a range of factors after the treatment commenced, and to test the relationship between ADMA and various inflammatory parameters.ResultsAnti-tumour necrosis factor alpha therapy significantly reduced ESR, CRP, fibrinogen and disease activity score 28 (all p < 0.001). ADMA levels did not change significantly following 2 weeks or 3 months treatment using three different tumour necrosis factor alpha inhibitors, despite the fact that CRP (p = 0.016), and DAS28 (p = 0.025) were found to be significantly associated with ADMA levels after treatment with TNFα antagonists.ConclusionADMA levels do not change significantly during anti-TNF therapy, despite the fact that they associate with CRP and DAS28, which are significantly reduced during such treatment in patients with rheumatoid arthritis. Levels of inflammation after treatment with TNFα antagonists are significantly associated with ADMA levels in patients with rheumatoid arthritis.     

Isotope dilution ultra performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 3-epi-25-hydroxyvitamin D3 in human serum

BackgroundAn ultra performance liquid chromatography-tandem mass spectrometry method with calibration traceable to NIST SRM was developed and validated to measure concentrations of 25-hydroxyvitamin D₂ (25OHD₂), 25-hydroxyvitamin D₃ (25OHD₃) and the C-3 epimer of 25OHD₃ (epi-25OHD₃) in human serum.MethodsTri- and hexa-deuterated internal standards were added to serum (100 μl) to monitor recovery. Liquid–liquid extraction was used to extract the hexane-soluble materials. Calibration solutions [8–100 nmol/L 25OHD_2, 12–150 nmol/L 25OHD₃, and 4–50 nmol/L epi-25OHD₃] prepared in phosphate-buffered saline containing 4% albumin were similarly processed. Using a pentafluorophenyl column (2.1 × 100 mm) and isocratic methanol/water (72/28, v/v) flowing at 0.4 ml/min, run time was 14 min per sample; 25OHD₃ and epi-25OHD₃ were baseline separated. Atmospheric pressure chemical ionization in the positive ion mode with selected reaction monitoring captured the following transitions: 25OHD₂, m/z 395.3 > 377.3 (209.1 qualifier); (epi-)25OHD₃, m/z 383.3 > 365.3 (105.1 qualifier); d₃-25OHD₂, m/z 398.3 > 380.3; and d₆-25OHD₃, m/z 389.3 > 371.3.ResultsRecovery averaged ≥ 98%. Total imprecision was ≤ 10% when concentrations were ≥ 20 nmol/l. Bias averaged < 5%. Detection limits were < 5 nmol/l. Median (nmol/l) 25OHD₂, 25OHD₃ and epi-25OHD₃ were quantitated in 98 blood donors (< LOD, 56.0, < LOD) and 35 pregnant women (< LOD, 87.6, 3.70).ConclusionsThis method is highly accurate, precise and specific.     

Correlation of haloperidol levels between saliva and plasma of acutely ill schizophrenic patients

ObjectiveClinical usefulness of monitoring haloperidol in salivary samples based on plasma:saliva correlation.Design and MethodsPlasma and saliva samples of schizophrenic patients [N = 105] were analyzed by highly sensitive reverse phase liquid chromatographic method to measure haloperidol at 240 nm using UV-PDA detector. Mobile phase consist of acetonitrile and water [50:50], pH 2.5 (0.1% acetic acid and 0.05 M KHPO₄) at flow rate 1.4 mL/min. Method was linear over 3–200 ng/mL.ResultsObserved therapeutic range was 5–19 ng/mL [11.66 ± 3.97] and 17–54 ng/mL [27.52 ± 11.51] for plasma and saliva respectively. Mean S:P was found to be 2.36.ConclusionCurrent study showed significantly high correlation [r = 0.93, p < 0.0001] between haloperidol levels in saliva and plasma with linear relationship. It is therefore concluded that monitoring of salivary concentration can be a clinically beneficial substitute. Patients showing clinical improvement [N = 90] were within salivary concentration range of 17–54 ng/mL, which can be an appropriate steady state monitoring range for haloperidol in saliva.     

Inhaled fentanyl citrate improves exercise endurance during high-intensity constant work rate cycle exercise in chronic obstructive pulmonary disease

ContextActivity limitation and dyspnea are the dominant symptoms of chronic obstructive pulmonary disease (COPD). Traditionally, efforts to alleviate these symptoms have focused on improving ventilatory mechanics, reducing ventilatory demand, or both of these in combination. Nevertheless, many patients with COPD remain incapacitated by dyspnea and exercise intolerance despite optimal therapy.ObjectivesTo determine the effect of single-dose inhalation of nebulized fentanyl citrate (a μ-opioid agonist drug) on exercise tolerance and dyspnea in COPD.MethodsIn a randomized, double-blind, placebo-controlled, crossover study, 12 stable patients with COPD (mean ± standard error of the mean post-β₂-agonist forced expiratory volume in one second [FEV₁] and FEV₁ to forced vital capacity ratio of 69% ± 4% predicted and 49% ± 3%, respectively) received either nebulized fentanyl citrate (50 mcg) or placebo on two separate days. After each treatment, patients performed pulmonary function tests and a symptom-limited constant work rate cycle exercise test at 75% of their maximum incremental work rate.ResultsThere were no significant postdose differences in spirometric parameters or plethysmographic lung volumes. Neither the intensity nor the unpleasantness of perceived dyspnea was, on average, significantly different at isotime (5.0 ± 0.6 minutes) or at peak exercise after treatment with fentanyl citrate vs. placebo. Compared with placebo, fentanyl citrate was associated with 1) increased exercise endurance time by 1.30 ± 0.43 minutes or 25% ± 8% (P = 0.01); 2) small but consistent increases in dynamic inspiratory capacity by ～0.10 L at isotime and at peak exercise (both P ≤ 0.03); and 3) no concomitant change in ventilatory demand, breathing pattern, pulmonary gas exchange, and/or cardiometabolic function during exercise. The mean rate of increase in dyspnea intensity (1.2 ± 0.3 vs. 2.9 ± 0.8 Borg units/minute, P = 0.03) and unpleasantness ratings (0.5 ± 0.2 vs. 2.9 ± 1.3 Borg units/minute, P = 0.06) between isotime and peak exercise was less after treatment with fentanyl citrate vs. placebo.ConclusionSingle-dose inhalation of fentanyl citrate was associated with significant and potentially clinically important improvements in exercise tolerance in COPD. These improvements were accompanied by a delay in the onset of intolerable dyspnea during exercise near the limits of tolerance.     

Relationship of age-related concentrations of serum FSH and LH with bone mineral density, prevalence of osteoporosis in native Chinese women

BackgroundFollicle-stimulating hormone (FSH) and luteinizing hormone (LH) may play an important role in bone mass regulation in postmenopausal women.MethodsA cross-sectional study of 699 healthy Chinese women, aged 20 to 82 y, was conducted. Serum FSH and LH and BMD were measured at the posteroanterior (PA) spine, lateral spine, total hip, and distal forearm.ResultsThe geometric mean values (± SD) of serum FSH and LH in premenopausal women were 3.94 ± 2.08 and 7.51 ± 2.58 IU/l, respectively, and in postmenopausal women were 28.8 ± 1.88 and 25.6 ± 1.95 IU/l, respectively. The correlation of FSH to BMD at different skeletal regions (r = ? 0.597 – ? 0.492, P = 0.000) was higher than that of LH to BMD (r = ? 0.452 – ? 0.332, P = 0.000). The prevalences of osteoporosis for the quartiles of FSH at various skeletal sites were 0.57%, 0.43%, 27.1%, and 30.9%, respectively; and of LH were 2.14%, 4.43%, 19.5%, and 26.0%, respectively. The prevalence of osteoporosis in 3rd and 4th quartile was more significantly increased than the 1st and 2nd quartile.ConclusionsThese data suggest that FSH and LH levels in circulation are associated with BMD changes and osteoporosis occurrence in Chinese women.     

Positive correlation between CD137 expression and complex stenosis morphology in patients with acute coronary syndromes

BackgroundCD137, a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed highly in patients with acute coronary syndromes. However, limited information is available on the relationship between CD137 expression and complex stenosis morphology in patients with acute coronary syndromes.MethodsOur study included normal controls (n = 50), patients with stable angina (SA) (n = 80) and patients with acute coronary syndromes (ACS), including unstable angina (UA) (n = 70) and acute myocardial infarction (AMI) (n = 100). The expression of CD137 in peripheral monocytes was analyzed by flow cytometry. Serum soluble CD137 (sCD137), MMP-9 and MMP-3 levels were measured by enzyme-linked immunosorbent assay kit. All coronary stenoses with ≥ 50% diameter reduction were assessed by angiographic coronary stenosis morphology.ResultsPatients with ACS(n = 170) showed a significant increase of CD137 [23.6 ± 5.7 mean fluorescence intensity (MFI)] expression in peripheral monocytes compared with control (8.4 ± 2.6 MFI) and SA group (7.9 ± 2.1 MFI) (p < 0.001). sCD137 also showed higher level in patients with ACS(30.2 ± 8.7 ng/ml) than in control (6.2 ± 1.8 ng/ml) and SA group (7.1 ± 2.1 ng/ml) (p < 0.001). Serum MMP-3 and MMP-9 in patients with ACS were 2-times greater than those in control and SA group. A positive correlation was found between MMP-9, MMP-3 and CD137 expression in peripheral monocytes as well as sCD137 levels. An obvious correlation was also observed between soluble or membrane-bound CD137 expression and complex coronary stenoses (r₁ = 0.5548, r₂ = 0.4652, and p < 0.001). In the logistic regression model, the independent predictors of ACS were sCD137 (odds ratio 2.671, 95% CI 1.718–4.153, P = 0.000), MMP-9 (1.431, 1.043–1.964, P = 0.026) and MMP-3 (1.368, 1.038–1.817, P = 0.018).ConclusionPatients with ACS showed significantly positive correlation between CD137 expression and complex coronary stenosis morphology. We speculate that the increased CD137 expression might represent or reflect an instability of atherosclerotic plaques in patients with ACS.     

Serum albumin is a useful prognostic indicator and adds important information to NT-proBNP in a Chinese cohort of heart failure

ObjectiveTo evaluate the effect of serum albumin on prognosis and the power of albumin adding information to NT-proBNP in a Chinese cohort of heart failure.Design and methods385 consecutive patients (male vs. female: 292 vs. 93; mean age: 54.89 ± 14.41 years; NYHA classes II–V) admitted for heart failure exacerbation with LVEF ≤ 45% were enrolled, and biochemical data was measured at baseline. The endpoint was defined as cardiac death or rehospitalization for aggravated heart failure. Follow-up period was 25 ± 7 months.ResultsMultivariate analysis in a Cox proportional hazard model revealed serum albumin was an independent predictor for adverse prognosis (HR 0.96,CI 0.94–0.99, P = 0.02), and the patients with higher NT-proBNP and lower albumin than median had the highest risk for cardiac events (HR 2.89, CI 1.90–4.40, P < 0.01).ConclusionSerum albumin is a significant prognosis indicator for heart failure and it adds important information to NT-proBNP.