Association of beta 1-adrenergic receptor gene polymorphisms with left ventricular hypertrophy in human essential hypertension

ObjectivesExperimental evidence support a key role for beta (1)-adrenergic receptor (ADRB1) in the modulation of cardiac mass. This relationship has not yet been described in Chinese population. The goal of our study was to investigate the relationships between ADRB1 gene polymorphisms and left ventricular structure in human essential hypertension.Design and methodsA total of 2417 hypertensive patients were successfully investigated. The polymorphisms of ADRB1 gene (Arg389Gly and Gly49Ser) were genotyped by using PCR-RFLP and confirmed by sequencing.ResultsPatients carrying the Arg389Arg genotype had an increase in the left ventricular septal thickness (10.4 ± 1.5 mm vs. 9.6 ± 1.5 mm, P < 0.01 or 9.4 ± 1.4 mm, P < 0.01); left ventricular posterior wall thickness (10.4 ± 2.4 mm vs. 9.6 ± 2.4 mm or 9.7 ± 2.9 mm, P < 0.01); left ventricular mass index (51.6 ± 13.3 g/m^2.7 vs. 44.6 ± 12.9 g/m^2.7, P < 0.01 or 43.2 ± 14.4 g/m^2.7, P < 0.01) and relative wall thickness (45.0 ± 9.0% vs. 42.6 ± 8.1%, P < 0.01 or 43.2 ± 8.8%, P < 0.01) as compared with those carrying genotypes Arg389Gly and Gly389Gly. These associations were independent of anthropometric factors and major clinical features and were replicated in another independent hypertensive population (n = 327).ConclusionsOur findings show that the Arg389Gly polymorphism of the ADRB1 gene confers higher risk of left ventricular hypertrophy in human essential hypertension.     

Prognostic value of extravascular lung water and its potential role in guiding fluid therapy in septic shock after initial resuscitation

PurposesTo explore whether extravascular lung water (EVLW) provides a valuable prognostic tool guiding fluid therapy in septic shock patients after initial resuscitation.Materials and MethodsWe performed a retrospective study of septic shock patients who achieved adequate initial fluid resuscitation with extended hemodynamic monitoring, analyzing the prognostic value of EVLW and whether fluid therapy for 24 (T₂₄) or 24-48 hours (T_24 -48) after initial resuscitation with a recommended value of EVLW yielded a 28-day mortality advantage.ResultsOne hundred five patients with septic shock were included in this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial resuscitation, the daily fluid balance (DFB; T₂₄: 2494 ± 1091 vs 1965 ± 964 mL [P = .011] and T_24 -48: 2127 ± 783 vs 1588 ± 665 mL [P < .001]) and daily maximum values of the EVLW index (EVLWI_max; T₂₄: 13.9 ± 3.7 vs 11.5 ± 3.2 mL/kg [P < .001] and T_24 -48: 14.4 ± 5.3 vs 12.0 ± 4.4 mL/kg [P < .001]) were significantly higher in nonsurvivors than in survivors. In multivariate regression analysis, the DFB (T₂₄: odds ratio [OR] 1.001 [P = .016] and T_24 -48: OR 1.001 [P = .008]), EVLWI_max (T₂₄: OR 2.158 [P = .002] and T_24 -48: OR 3.277 [P = .001]), blood lactate (T₂₄: OR 1.368 [P = .021] and T_24 -48: OR 4.112 [P < .001]), and central venous blood oxygen saturation (T₂₄: OR 0.893 [P = .013] and T_24 -48: OR 0.780 [P = .004]) were all independently associated with the 28-day mortality. A receiver operating characteristic analysis revealed that area under the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90 (95% confidence interval, 0.83-0.96; P < .001) for EVLWI_max ≥ 12.5 mL/kg (T₂₄ and T_24 -48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and 95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWI_max was correlated with DFB with Spearman ρ values of 0.497 (T₂₄: P < .001) and 0.650 (T_24 -48: P < .001). Cox survival and regression analyses demonstrated that EVLWI_max ≥ 12.5 mL/kg (T₂₄ and T_24 -48) was associated with higher risk and increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001).ConclusionsA higher EVLW in septic shock patients after initial resuscitation was associated with a more positive fluid balance and increased mortality, which is an independent predictor of the 28-day mortality in septic shock patients after initial resuscitation.     

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).     

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.     

Plasma HDL-cholesterol and triglyceride levels in familial hypercholesterolemia: data from the MedPed CZ database and the Czech population

BackgroundThe aim of this study was to compare HDL-cholesterol and triglyceride levels in patients with familial hypercholesterolemia (FH) with a representative sample of the Czech population.MethodsFor the FH group: data of 1728 adult patients with FH (600 males and 1128 females) were taken from the MedPed CR database. The control group were 1995 individuals of the population sample of the Czech post-MONICA study (956 males and 1039 females).ResultsCompared with controls, FH males showed higher levels of HDL-cholesterol (1.35 ± 0.35 mmol/l vs. 1.31 ± 0.35 mmol/l; P < 0.05) and triglycerides (1.98 ± 1.00 vs. 1.81 ± 1.45 mmol/l; P < 0.01). After adjustment for age and BMI, the increase in triglycerides remained significant in the subgroup of non-FDB males only (2.22 ± 0.06 vs. 1.74 ± 0.04 mmol/l; P < 0.001). Compared with controls, HDL-cholesterol was lower (1.55 ± 0.40 mmol/l vs. 1.65 ± 0.37 mmol/l; P < 0.001), while triglycerides were higher (1.72 ± 0.82 mmol/l vs. 1.28 ± 0.75, P < 0.001) in FH females. After adjustment for age and BMI, HDL-cholesterol remained lower in the subgroup of FH females without FDB (1.52 ± 0.01 vs. 1.67 ± 0.01 mmol/l, P < 0.001) whereas triglycerides were higher in both female subgroups.ConclusionsA lower HDL-C in the group of FH patients compared with control subjects was demonstrated in FH females without FDB only. Elevated triglyceride levels were found in FH males and females, except for males with FDB.     

Detection of serum β2-GPI–Lp(a) complexes in patients with systemic lupus erythematosus

BackgroundCirculating β₂-glycoprotein-I-oxidized low-density lipoprotein (β₂-GPI–ox-LDL) complexes have been found in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases as a contributor to the development of autoimmune-mediated atherosclerosis. In vitro study showed that β₂-GPI also bound with high affinity to atherogenic lipoprotein (a) [Lp(a)] which shares structural similarity to LDL. We examined the existence and clinical significance of serum complexes of β₂-GPI with Lp(a) in SLE patients.MethodsA “sandwich” ELISA was developed for measuring serum concentrations of β₂-GPI–Lp(a) complexes, using rabbit anti-human β₂-GPI antibody as capturing antibody, and quantitating with antibody against apo(a). Forty-seven SLE patients and 42 healthy controls were studied.ResultsBoth Lp(a) (400 ± 213 mg/l vs. 181 ± 70 mg/l) and ox-Lp(a) (27.07 ± 22.30 mg/l vs. 8.20 ± 4.55 mg/l) concentrations were higher in SLE patients than in controls (P < 0.0001). β₂-GPI–Lp(a) complexes were detectable in both controls and SLE. The complexes levels in SLE were higher than in controls (0.96 ± 0.41 U/ml vs. 0.59 ± 0.20 U/ml, P < 0.0001) and was positively correlated with ox-Lp(a) (P < 0.001).ConclusionsWe report the existence of β₂-GPI–Lp(a) complexes in both controls and SLE patients. The complexes levels increase in SLE.     

A ventilation technique for oxygenation and carbon dioxide elimination in CPR: Continuous insufflation of oxygen at three levels of pressure in a pig model

AimPulmonary ventilation remains an important part of cardiopulmonary resuscitation, affecting gas exchange and haemodynamics. We designed and studied an improved method of ventilation for CPR, constructed specifically to support both gas exchange and haemodynamics. This method uses continuous insufflation of oxygen at three levels of pressure, resulting in tri-level pressure ventilation (TLPV). We hypothesized that TLPV improves gas exchange and haemodynamics compared to manual gold standard ventilation (GSV).MethodsIn 14 pigs, ventricular fibrillation was induced and automated CPR performed for 10 min with either TLPV or GSV. After defibrillation, CPR was repeated with the other ventilation method. Gas exchange and haemodynamics were monitored. Data are presented as mean ± standard error of the mean.ResultsTLPV was superior to GSV for PaO₂ (163 ± 36 mmHg difference; P = 0.001), and peak AWP (−20 ± 2 cmH₂O difference; P = 0.000) and higher for mean AWP (8 ± 0.2 cmH₂O difference; P = 0.000). TLPV was comparable to GSV for CPP (5 ± 3 mmHg difference; P = 0.012), VCO₂ (0.07 ± 0.3 mL/min/kg difference; P = 0.001), SvO₂ (4 ± 3%-point; P = 0.001), mean carotid flow (−0.5 ± 4 mL/min difference; P = 0.016), and pH_a (0.00 ± 0.03 difference; P = 0.002). The PaCO₂ data do not provide a conclusive result (4 ± 4 mmHg difference).ConclusionWe conclude that the ventilation strategy with a tri-level pressure cycle performs comparable to an expert, manual ventilator in an automated-CPR swine model.     

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.     

Quality of life and brace-treated idiopathic scoliosis: a cross-sectional study performed at the Centre des Massues on a population of 120 children and adolescents

ObjectivesTo determine the influence of orthopedic treatment on quality of life (QoL) in children and adolescents with idiopathic scoliosis and treated with either the carbon brace (CMCR, corset monocoque carbone respectant la respiration) or the Lyon brace. To compare these braces.Patients and methodsA cross-sectional study on a population of 120 patients with idiopathic scoliosis, visiting for routine evaluation following the onset of an orthopedic treatment at the Centre des Massues in Lyon. Eighty-two patients used the carbon brace and 38 patients used the Lyon brace. The patients completed the SRS-22 questionnaire (where a low score means a bad QoL), an evaluation scale of QoL specific to spinal deformities, and visual analogue scales (VAS) for pain, motivation and QoL ranging from 0 to 100 mm.ResultsThe QoL of Lyon brace-treated patients is significantly worse than that of patients treated with a carbon brace for the overall score (mean ± SD, 4.05 ± 0.37 vs 3.77 ± 0.46, P = 0.002) as well as for function (P = 0.01), pain (P = 0.001), and appearance (P = 0.004). These results are confirmed by the VAS for QoL (P = 0.001).ConclusionThe use of the carbon brace and of the Lyon brace induces a reduction in QoL whatever the evaluation tool, either SRS-22 or VAS. However, the use of the Lyon brace impairs QoL more than the use of the carbon brace.     

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.     

Interethnic differences in ADMA concentrations and negative association with nitric oxide formation in preeclampsia

BackgroundRecent studies have suggested that impaired nitric oxide (NO) formation in preeclampsia may result from increased concentrations of an endogenous NO synthase inhibitor, the asymmetric dimethylarginine (ADMA). However, no previous study has examined whether a negative association exists between ADMA and nitrite concentrations in preeclampsia. Moreover, no previous study has compared ADMA and nitrite levels in black and white preeclamptic pregnant women.MethodsWe measured plasma nitrite concentrations using an ozone-based chemiluminescence assay, and plasma ADMA levels using enzyme immunoassays in 94 pregnant (47 healthy pregnant: 16 blacks and 31 whites; and 47 preeclamptic: 14 blacks and 33 whites).ResultsWe found higher ADMA (2.199 ± 0.016 μmol/l vs. 2.112 ± 0.012 μmol/l; P < 0.0001) and lower plasma nitrite levels (102 ± 7.1 nmol/l vs. 214.8 ± 26.1 nmol/l; P < 0.0001) in preeclamptic compared with healthy pregnant women. Black pregnant had higher ADMA levels than white pregnant women (P < 0.05), both in preeclamptic (2.239 ± 0.020 μmol/l vs. 2.144 ± 0.019 μmol/l) and in healthy pregnant (2.172 ± 0.025 μmol/l vs. 2.077 ± 0.018 μmol/l). Conversely, we found no significant effects of ethnicity on the plasma nitrite levels, both in healthy pregnant and in preeclamptic women (P > 0.05). We found a significant negative correlation (P < 0.05) between these markers (r = ? 0.28; P < 0.05).ConclusionsOur findings show higher ADMA and lower nitrite levels in preeclamptic compared with healthy pregnant, and the concentrations of these biomarkers are inversely associated. While ethnicity affected ADMA concentrations, no such effect was found with respect to nitrite levels. These results may have important implications for studies on NO biology and therapeutic approaches of preeclampsia.     

Vital and functional outcomes of the first-ever hemispheric stroke, epidemiological comparative study between Kunming (China) and Limoges (France)

BackgroundClinical outcomes and socioeconomic consequences after a stroke may differ between regions.MethodsOne cohort was established prospectively in Kunming (China) to compare with a cohort of 156 stroke patients included in Limoges (France). During 1 year, patients hospitalized within 48 hours for a first-ever hemispheric stroke were included. Demographic data and neurocardiovascular risk factors were registered. Hemiplegia was evaluated. Functional outcome was assessed using the Barthel Index (BI) after 3 months.ResultsOne hundred and eighteen patients were included in Kunming. Patients of Kunming were younger (61.4 ± 13.4 vs 72.3 ± 14.6 years in Limoges, P < 0.0001), more involved in professional activity (36.4% vs 12.8%, P < 0.0001). Survival analysis indicated that mortality did not differ between cohorts, but independently predicted by coma at the 2nd day (HR = 9.33, 95% CI [4.39, 19.78]) and age > 70 years (HR = 6.29, 95% CI [2.36, 16.59]). Despite a better baseline BI for patients of Kunming (50.0 ± 34.9 vs 37.4 ± 34.2, P = 0.0031), after adjustment for confusing, patients in Limoges had a 2.11 OR 95% CI [1.03, 4.31]) to reach a BI > 80 at 3 months.ConclusionsFunctional recovery for patients of Kunming was not as good as expected. The socioeconomic consequences of stroke in Kunming are significant as they involved younger subjects who were still in work.     

Analysis of amplitude spectral area and slope to predict defibrillation in out of hospital cardiac arrest due to ventricular fibrillation (VF) according to VF type: Recurrent versus shock-resistant

BackgroundIn out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF), VF may recur during resuscitation (recurrent VF) or fail to defibrillate (shock-resistant VF). While retrospective studies have suggested that amplitude spectral area (AMSA) and slope predict defibrillation, it is unknown whether the predictive power is influenced by VF type. We hypothesized that in witnessed OHCA with initial rhythm of VF that the utility for AMSA and slope to predict defibrillation would differ between shock-resistant and recurrent VF.MethodsAMSA and slope were measured immediately prior to each shock. For second or later shocks, VF was classified as recurrent or shock-resistant. Cardiac arrest was classified according to whether the majority of shocks were for recurrent VF or shock-resistant VF.Results44 patients received 98 shocks for recurrent VF and 96 shocks for shock-resistant VF; 24 patients achieved ROSC in the field. AMSA and slope were higher in recurrent VF compared to shock-resistant VF (AMSA: 28.8 ± 13.1 vs 15.2 ± 8.6 mV Hz, P < 0.001, and slope: 2.9 ± 1.4 vs 1.4 ± 1.0 mV s^?1, P = 0.001). Recurrent VF was more likely to defibrillate than shock-resistant VF (P < 0.001). AMSA and slope predicted defibrillation in shock-resistant VF (P < 0.001 for both AMSA and slope) but not in recurrent VF. Recurrent VF predominated in 79% of patients that achieved ROSC compared to 55% that did not (P = 0.10).ConclusionsIn witnessed OHCA with VF as initial rhythm, recurrent VF is associated with higher values of AMSA and slope and is likely to re-defibrillate. However, when VF is shock-resistant, AMSA and slope are highly predictive of defibrillation.     

Effect of somatostatin analogue octreotide on pain relief after major abdominal surgery

BackgroundOctreotide acetate is an 8-amino-acids synthetic octapeptide analogue of somatostatin with much-enhanced duration of action and lower incidence of side effects. We assessed the utility of using intravenous octreotide as an adjuvant to opioid analgesia that might exert a post-operative opioid-sparing effect.MethodsForty-four patients were randomly allocated, to receive either a placebo or intraoperative octreotide 0.33 μg kg^?1 h^?1 intravenous infusion that was maintained in the post-operative period. Patients received for post-operative analgesia an intravenous piritramide patient controlled analgesia (PCA), set to deliver a piritramide 0.02 mg kg^?1 dose.ResultsTwo-way ANOVA revealed significantly fewer (P = 0.0003) mean ± SD weighted piritramide dose requirements in the octreotide group (19.5 ± 6.3 μg kg^?1 h^?1) than in the control group (35.7 ± 8.2 μg kg^?1 h^?1). Dunnett’s two-sided multiple-comparison post hoc test revealed a significant difference between the two groups during the first 22 post-operative hours, following which there were no differences between the two groups. There were no significant differences over time in the mean arterial pressure (P = 0.722), heart rate (P = 0.579) and respiratory rate (P = 0.823) between the octreotide group (80 ± 10 mm Hg, 74 ± 12, 14 ± 2) and the control group (82 ± 9 mm Hg, 76 ± 11, 15 ± 3), respectively.ConclusionWe demonstrated that perioperative octreotide intravenous infusion could be an adjuvant to opioid analgesia as it exerted a piritramide opioid-sparing effect. We encountered more systemic side effects such as nausea, abdominal discomfort, and diarrhea in the octreotide group than in the control group. Our findings could be beneficial to patients who cannot tolerate the adverse effects of opioids.     

Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans

BackgroundA single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A₂ (Lp-PLA₂) gene is known to influence enzyme activity. It is unclear whether Lp-PLA₂ exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA₂ activity, oxidative stress and inflammation.MethodsWe genotyped 2914 healthy Koreans (43–79 years) for the Lp-PLA₂ V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA₂ levels.ResultsLp-PLA₂ activity was 24% lower in V/F subjects (n = 641) than in those with the V/V genotype (n = 2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA₂ activity was positively correlated with LDL-cholesterol (r = 0.134, P < 0.001), ox-LDL (r = 0.064, P < 0.01), 8-epi-PGF_2α (r = 0.198, P < 0.001), free fatty acid (r = 0.082, P < 0.001), and fibrinogen (r = 0.112, P < 0.01) levels. Additionally, ox-LDL, 8-epi-PGF_2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9 ± 0.69, V/F: 119.4 ± 1.26, F/F: 109.2 ± 4.84 mg/dl, P = 0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥ 130 mg/dl) (P = 0.003) but not in those with low LDL-cholesterol (< 130 mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25 ± 0.09, V/F: 0.97 ± 0.12, F/F: 3.20 ± 0.88 mg/dl, P < 0.001).ConclusionsThe recessive effects of Lp-PLA₂ V279F on LDL-cholesterol and significant correlations between Lp-PLA₂ activity and LDL-cholesterol, 8-epi-PGF_2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA₂ activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.     

AgNORs count and DNA ploidy in liver biopsies from patients with schistosomal liver cirrhosis and hepatocellular carcinoma

ObjectivesArgyrophilic nucleolar organizer regions (AgNOR) proteins are a set of argyrophilic nucleolar proteins that accumulate in highly proliferating cells, whereas their expression is very low in nonproliferating cells. The present study aimed to investigate the potential of DNA flow cytometry (FCM) and AgNORs count in the assessment of cellular kinetics of liver cirrhosis and hepatocellular carcinoma.Design and methodsSmall-needle liver biopsies (217) were included and were taken from 84 patients with hepatocellular carcinoma (HCC) (one biopsy from tumor lesion and the other from residual nontumor) liver tissues. Only one biopsy was taken from 49 patients with liver cirrhosis. One part of biopsy was subjected to flow cytometry, and the other, to histopathology and AgNORs counting.ResultsAn aneuploidy was shown in 44.5% of liver cirrhosis and in 78.6% of tumor sites. Aneuploid HCC cases showed high AgNORs count compared with diploid cases (3.407 ± 1.18 vs. 1.74 ± 0.9). An extremely significant increase in AgNORs count in tumor lesion (P < 0.001) was found compared with residual liver tissues, liver cirrhosis and normal liver (3.89 ± 0.827, 1.49 ± 0.52, 1.62 ± 0.29, and 1.3 ± 0.17, respectively). In liver cirrhosis, dysplasia showed a significant relationship with ploidy (P < 0.001) and AgNORs count (P < 0.05).ConclusionAgNORs count and DNA ploidy analysis of core biopsy specimens are useful in the assessment of cellular kinetics of liver cirrhosis and hepatocellular carcinoma.     

The mouth-to-bag resuscitator during standard anaesthesia induction in apnoeic patients

AimVentilation of a non-intubated emergency patient by inexperienced rescuers with a standard bag-valve device may result in high inspiratory flow rates and subsequently high airway pressures with stomach inflation. Therefore, a self-inflating bag has been developed that requires lay rescuers to blow up a single-use balloon inside an adult bag-valve device, which, in turn, displaces air within the bag towards the patient. This concept has been compared to standard adult bag-valve devices earlier in bench models but not in patients.MethodsAn anaesthetist who was blinded to all monitor tracings ventilated the lungs of 40 apnoeic patients during routine anaesthesia induction either with a standard bag-valve device or with the mouth-to-bag resuscitator in a random order. Study endpoints were peak inspiratory flow rates, peak airway pressure, tidal volumes and inspiratory time.ResultsPeak inspiratory flow was 40 ± 10 l min^?1 for the standard bag-valve device versus 33 ± 13 l min^?1 for the mouth-to-bag resuscitator (P < 0.0001); peak airway pressure was 17 ± 5 cmH₂O versus 14 ± 5 cmH₂O (P < 0.0001); inspiratory tidal volume was 477 ± 133 ml versus 644 ± 248 ml (P < 0.001) and inspiratory time was 1.1 ± 0.3 s versus 1.9 ± 0.6 s (P < 0.0001).ConclusionEmploying the mouth-to-bag resuscitator during simulated ventilation of a non-intubated patient in respiratory arrest significantly decreased peak inspiratory flow and peak airway pressure and increased inspiratory tidal volume and inspiratory times compared to a standard bag-valve device.     

Pressure attenuation during high-frequency airway clearance therapy across different size endotracheal tubes: An in vitro study

PurposeHigh-frequency airway clearance therapy is a positive pressure secretion clearance modality used in pediatric and adult applications. However, pressure attenuation across different size endotracheal tubes (ETT) has not been adequately described. This study quantifies attenuation in an in vitro model.Materials and methodsThe MetaNeb® System was used to deliver high-frequency pressure pulses to 3.0, 4.0, 6.0 and 8.0 mm ID ETTs connected to a test lung during mechanical ventilation. The experimental setup included a 3D-printed trachea model and imbedded pressure sensors. The pressure attenuation (P_att%) was calculated: P_att% = [(P_proximal–P_distal)/P_proximal]x100. The effect of pulse frequency on P_distal and P_proximal was quantified.ResultsP_att% was inversely and linearly related to ETT ID and (y = − 7.924x + 74.36; R² = 0.9917, P = .0042 for 4.0 Hz pulse frequency and y = − 7.382 + 9.445, R² = 0.9964, P = .0018 for 3.0 Hz pulse frequency). P_att% across the 3.0, 4.0, 6.0 and 8.0 mm I.D. ETTs was 48.88 ± 10.25%, 40.87 ± 5.22%, 27.97 ± 5.29%, and 9.90 ± 1.9% respectively. Selecting the 4.0 Hz frequency mode demonstrated higher P_proximal and P_distal compared to the 3.0 Hz frequency mode (P = .0049 and P = .0065). Observed P_distal was < 30cmH₂O for all experiments.ConclusionsIn an in vitro model, pressure attenuation was linearly related to the inner diameter of the endotracheal tube; with decreasing attenuation as the ETT size increased.