Contemporary outcomes of percutaneous closure of patent ductus arteriosus in adolescents and adults

BackgroundCatheter based treatment has gained wide acceptance for management of patent ductus arteriosus (PDA) ever since its introduction. Percutaneous closure in adults can be challenging because of anatomical factors including large sizes, associated pulmonary arterial hypertension (PAH) and co-morbidities. This study aimed to provide comprehensive contemporary data on the safety and efficacy of percutaneous device closure of PDA in adult and adolescent population at a large referral center.MethodsThis single-center retrospective analysis included 70 patients (33 adolescents and 37 adults) who underwent successful percutaneous device closure of PDA between January 2011 and February 2017.Baseline patient demographics, clinical characteristics, procedural and device related variables, and immediate outcomes during hospital stay were recorded. Patients were followed up for residual shunt and complications.ResultsOf 70 PDA device closure cases, 71.4% were females; the mean age was 23 years (range:10-58years). Devices used were 4-Cook’s detachable coils, 64-occluders (ADO-I and II, Lifetech, Cardi-O-Fix), 1-vascular plug and 1-ventricular septal occluder device. Device success was achieved in all including those with very large PDAs. At 24-h post-procedure, the success rate of transcatheter intervention was 95.7%. At 6-months follow up, complete closure was observed in all (mean follow up duration-531 days). In patients with severe PAH, significant immediate and sustained reduction of the mean pulmonary pressure was observed(77 mmHg to 33 mmHg;P = 0.014). No procedure-related complications including death, device embolization and stenosis of aorta or pulmonary artery occurred.ConclusionsIn contemporary practice, percutaneous device closure is an effective and safe treatment option for adolescent and adult PDA patients.     

Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros?

BackgroundIt is important which medicine to use as a first-line treatment to close the duct.ObjectivesThe aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA).MethodsOur study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol.ResultsOf these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212).ConclusionsOur results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.     

Evaluation of possible subclinical atherosclerosis in adolescents with a family history of premature atherosclerosis

ObjectiveTo evaluate possible subclinical atherosclerosis using biomarkers and ultrasound-guided methods in a group of adolescents having fathers with premature atherosclerosis.MethodsThirty-three subjects whose fathers had a history of premature coronary artery disease and 30 counterparts whose fathers had no history of coronary artery disease were included in the study.ResultsThe homocysteine levels, high-sensitivity C-reactive protein levels, and cardiac chamber sizes and functions did not differ between the two groups. The carotid stiffness index β (CSI), the intima-media thickness (CIMT) and aortic pulse wave velocity (PWV) values were higher in the group with a family history of coronary artery disease, but only the difference in the CSI was statistically significant (CSI 3.07 ± 1.33 vs 3.88 ± 1.25, P = 0.015; CIMT 0.53 ± 0.09 mm vs 0.57 ± 0.08 mm, P = 0.068; PWV 3.49 ± 0.53 m/s vs 3.78 ± 0.63 m/s, P = 0.053).ConclusionAmong several markers of subclinical atherosclerosis, the CSI was significantly higher in adolescents who had a family history of premature atherosclerosis. The small sample size, the multifactorial nature of atherosclerosis or the insufficient power of these methods may explain these results.     

Visualization of patent ductus arteriosus using real-time three-dimensional echocardiogram: Comparative study with 2D echocardiogram and angiography

PurposeTo determine the feasibility and accuracy of real time 3D echocardiography (RT3DE) in determining the dimensions and anatomical type of the patent ductus arteriosus (PDA).MethodsThe study included 42 pediatric patients with a mean age of 3.6 years (ranging from 2 months to 14 years) who were referred for elective percutaneous PDA closure. All patients underwent full 2D echocardiogram as well as RT3DE with off line analysis using Q lab software within 6 h from their angiograms. The PDA was studied as regard the anatomical type, length of the duct as well as the ampulla and the pulmonary end of the PDA. Data obtained by RT3DE was compared against 2D echocardiogram and the gold standard angiography.ResultsOffline analysis of the PDA was feasible in 97.6% of the cases while determination of the anatomical type using gated color flow 3D acquisitions was achieved in 78.5% of the cases. The pulmonary end of the duct was rather elliptical using 3D echocardiogram. There was significant difference between the pulmonary end measured by 3D echocardiogram and angiography (P < 0.001). There was no significant difference between either the length or the ampulla of the PDA measured by 3D echocardiogram and that measured by angiography (P value = 0.325 and 0.611, respectively). There was a good agreement between both 2D or 3D echocardiogram and angiography in determining the anatomical type of the PDA (K = 0.744 and 0.773, respectively). However 3D echocardiogram could more accurately determine type A and type E ductus compared to 2D echocardiogram.Conclusion3D echocardiogram was more accurate than 2D echocardiogram in determining the length and the ampulla of the PDA. The morphologic assessment of the PDA using gated 3D color flow was achieved in 78.5% of the patients. Nevertheless the use of 3D echocardiogram in assessment of small vascular structures like PDA in children with rapid heart rates is still of limited clinical value.     

Predictive Value of Blood N-Terminal Pro-Brain Natriuretic Peptide Concentrations for Early Patent Ductus Closure in Very Preterm Infants

ObjectivesIt has been shown that blood concentrations of NT-proBNP may be useful in identifying preterm infants at risk of hemodynamically significant patent ductus arteriosus and its complications. The aim of the study was to assess predictive value of serum NT-proBNP levels for early ductus arteriosus (DA) closure in very preterm newborns.MethodsFifty-two infants <32 weeks’ gestation aged <72 hours with patent ductus arteriosus (PDA) diameter >1.5 mm were involved in a randomized study. Twenty-seven (52%) of them were treated with ibuprofen or paracetamol starting within the first 3 days of life. Expectant management was applied to 25 (48%) infants. All patients underwent planned echocardiographic (daily) and two serum NT-proBNP measurements within the first 10 days after birth. Depending on the DA closure within the first 10 days of life, 2 groups of patients were formed retrospectively, with closed (n = 30) or patent (n = 22) DA by this age.ResultsIn the first 10 days of life, DA closure occurred in 19 (70%) treated infants and in 11 (44%) infants managed expectantly (p > 0,05). Initial concentrations of NT-proBNP were significantly higher in infants that had patent ductus arteriosus (PDA) at 10 days of life. By the eighth day, median NT-proBNP values in both groups significantly decreased but remained considerably higher in newborns with PDA. NT-proBNP serum concentrations on the second day of life could reliably predict DA closure within the first 10 days after birth in treated babies (the AUC was significant 0.81 [95% CI: 0.58–1.03], p < 0.05) but not in infants who were managed expectantly.ConclusionsSerum NT-proBNP concentrations on the second day of life could reliably predict early PDA closure in treated but not in expectantly managed very preterm infants.     

Stenting of patent ductus arteriosus in low birth weight newborns less than 2 kg- procedural safety,feasibility and results in a retrospective study

ObjectiveRetrospective analysis of the feasibility, safety and results of patent ductus arteriosus (PDA) stenting in low birth weight babies weighing < 2 kg. Background: Stenting of patent ductus arteriosus is a well known palliative technique for several years as an alternative to shunt surgery in babies weighing > 2.5–3 kg. Ductal stenting in babies weighing less than 2 kg is not done routinely all around the world due to limited experience and concerns regarding its feasibility and safety in such small subset.MethodsRecords of patients who underwent PDA stenting at our institution from June 2014 to December 2016 were reviewed. In this period, we attempted to do PDA stenting using femoral artery approach in babies weighing < 2 kg. Echocardiography and colour Doppler were used for patient selection and assessment of procedural outcome.ResultsPDA stenting using femoral artery approach was successful in all 5 patients weighing < 2 kg. In this group, patient age ranged from 2 days to 16 days and weighed 1.8 kg to 1.97 kg. All patients had good post-procedure outcome. One patient had stent malposition from aortic end towards main pulmonary artery which was managed by an additional stent.ConclusionPDA stenting is feasible and safe with good end results in carefully selected low birth weight babies weighing < 2 kg.     

Percutaneous transcatheter closure of patent ductus arteriosus: Initial experience of Sohag University

ObjectivesInitial experience with transcatheter closure of patent ductus arteriosus (PDA) using different types of devices is reported in Sohag University Hospital. We evaluated the outcome, complications, and also assessed the need of surgical backup for such interventional procedures.MethodsFrom March 2011 to September 2012, 51 patients who underwent transcatheter closure of PDA, were retrospectively identified and studied. Aortic angiogram was performed to evaluate the size, position, and shape of the duct for appropriately choosing the occluder device type and size. A second aortic angiogram was performed 10 min after device deployment. Echocardiography was repeated at intervals of 24 h, then at 1, 3, and 6 months after the procedure to assess complications. The PDA was closed by Amplatzer Duct Occluder (ADO) in 40 patients, Nit occlude PFM coil in five patients, Amplatzer muscular VSD in two patients and Detachable Cook coil in four patients .ResultsOf 51 cases, one patient had left pulmonary artery embolization of ADO that required surgical intervention. The PDA was successfully closed in 98.04% of the study population without any residual PDA shunting. All the patients were alive. Infants made up 29% of the total patients. 45 patients were children and six patients were adults.ConclusionOur initial results show that transcatheter occlusion of PDA using different types of devices is safe and effective with good midterm outcome alternative to surgery. Complications occurred in those with unfavorable duct anatomy and presence of pulmonary hypertension. Surgical backup was not important for such interventional procedures.     

Early decrease in resting energy expenditure with bedtime insulin therapy

AimsIn type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients.MethodsAfter improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n = 10, group 1); and one off (3-day) intravenous insulin infusion (n = 10, group 2).ResultsBoth groups were similar in age, gender, BMI, C-peptide, HbA_1c and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: −5.3 ± 2.7 mmol/L vs group 2: −5.8 ± 4.2 mmol/L. In group 2, the second REE was measured 12 h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (−1.3 ± 6.5%), whereas it decreased significantly in group 1 (−8.0 ± 7.0%; P < 0.05).ConclusionBedtime insulin led to an early and specific reduction in REE.     

Cardiac autonomic regulation during gastroscopy

BackgroundGastroscopy is sometimes associated with adverse cardiovascular events.AimsWe evaluated the effects of sedation and pharyngeal anaesthesia on cardiac autonomic regulation during gastroscopy.PatientsTwo hundred thirteen outpatients undergoing gastroscopy.MethodsThe patients were assigned to 4 groups: (1) sedation with intravenous midazolam and placebo throat spray (midazolam group), (2) placebo sedation and pharyngeal anaesthesia with lidocaine (lidocaine group), (3) placebo sedation and placebo throat spray (placebo group), and (4) no intravenous cannula nor throat spray (control group). Continuous electrocardiogram was recorded. Heart rate variability was assessed; the powers of low frequency (0.04–0.15 Hz) and high frequency (0.15–0.40 Hz) components as well as total power (0.0–0.40 Hz) were calculated.ResultsGastroscopy was associated with a decrease in high frequency normalized units, increases in low frequency normalized units and low frequency/high frequency ratio indicating activation of sympathetic and withdrawal of vagal modulation. Sympathetic activation resulted in a decrease in total power and all components of heart rate variability. The decrease was most prominent in the midazolam treated patients (p < 0.001 vs the lidocaine group and p < 0.01 vs placebo and control groups during the postendoscopy phase).ConclusionGastroscopy induces a shift towards dominance of the sympathetic modulation of the heart. Premedication with midazolam potentiates this shift.     

Closure of the ductus arteriosus with indomethacin in ventilated neonates with respiratory distress syndrome. Effects of pulmonary compliance and ventilation

The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.     

Single-dose prophylactic ibuprofen therapy for patent ductus arteriosus in preterm infants

This study aimed to evaluate the short-term morbidities and efficacy of single-dose prophylactic intravenous ibuprofen for patent ductus arteriosus (PDA) on the first day of life in preterm infants.Data of 69 preterm infants with birth weight < 1250 g and gestational age < 30 weeks admitted to the neonatal intensive care unit were analyzed. Of these, 37 infants were assigned to the prophylactic treatment (PT) group and 32 were assigned to the nonprophylactic treatment (non-PT) group. Only the PT group administered intravenous ibuprofen (10 mg/kg) once within 6 hours after birth.Until postnatal day 7, ductal closure occurred in 11 (34.4%) infants in the non-PT group, and in 35 (94.6%) infants in the PT group, of which 30 (81.1%) infants had ductal closure on postnatal day 1. There were 2 (5.4%) infants in the PT group and 9 (28.1%) in the non-PT group who needed ibuprofen treatment due to moderate-to-large PDA after postnatal day 7. Preterm infants in the PT group were less likely to develop an intraventricular hemorrhage (≥grade 2) (adjusted odds ratio 0.007, 95% confidence interval 0.01–0.45), had a shorter duration of invasive ventilatory support and central venous catheter, and earlier postnatal age to achieve feeding of 50 and 100 mL/kg/day compared with those in the non-PT group.Single-dose prophylactic intravenous ibuprofen on the first day of life decreased the occurrence of a persistent PDA and intraventricular hemorrhage (≥grade 2), and reduced the duration of invasive ventilatory support, central venous catheter use, and hospital stay.     

Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions

Objective: To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus(PDA) in premature neonates with significant clinical and hemodynamic repercussions(CHRs) and to determine the effect of these respective treatments on renal function.Methods: A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin[0.2 mg/(kg$d), 3-day cycle], ibuprofen [10 mg/(kg$d) followed by 5 mg/(kg$d), 3-day cycle], and paracetamol(15 mg/kg every 6 h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age,newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels(sodium and potassium).Results: Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5 d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of9.66 d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus.Conclusions: Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective.However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.     

Outcomes of Percutaneous Closure of Patent Ductus Arteriosus Accompanied With Unilateral Absence of Pulmonary Artery

Background

Limited data have reported the outcomes of percutaneous closure of patent ductus arteriosus (PDA) in patients with unilateral absence of pulmonary artery (UAPA). This study aimed to evaluate the symptomatology, diagnosis and therapy, especially the transcatheter closure of PDA in patients with PDA associated with UAPA.

Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study

ObjectivesTo investigate the extent of subclinical atherosclerosis in asymptomatic familial hypercholesterolemia (FH) patients using non-invasive images techniques.Patients, methods and resultsThe atherosclerotic burden of 36 molecularly defined FH patients (18 males, 45.7 ± 10.9 years) without evidence of cardiovascular disease receiving lipid-lowering treatment and 19 (47.8 ± 11.3 years) controls was investigated. Descending thoracic aorta magnetic resonance imaging (MRI) was performed in a 1.5 T equipment with T1 and T2 sequences to characterize atherosclerotic plaques and to measure aortic wall volumen. Carotid intima-media thickness (cIMT) and presence of plaques were measured using B-mode carotid ultrasound.Mean aortic wall volumen, cIMT and atherosclerotic plaques in aorta were significantly higher in FH cases (P < 0.001). A significant correlation between aortic wall volume and cIMT was observed (P < 0.01). Aortic MRI detected plaques in 94% and carotid ultrasound in 14% of cases. Lipid-rich plaques were observed only in FH cases (33%) and were associated with family history of premature coronary artery disease (P < 0.05).ConclusionsAsymptomatic middle-aged FH patients have significantly higher atherosclerotic burden than controls. cIMT has shown a significant correlation with aortic wall volume and MRI allowed the detection of lipid-rich plaques in FH subjects that were associated with family history of premature coronary artery disease.     

Patent ductus arteriosus in preterm newborns: A tertiary hospital experience

IntroductionPatent ductus arteriosus (PDA) in preterm infants has been associated with increased mortality and comorbidities. This study aimed to characterize the population of preterm infants diagnosed with PDA and to identify predictive factors of response to medical treatment of PDA.MethodsAn eight-year retrospective observational study was carried out, which included all preterm infants with a gestational age (GA) between 23 and 32 weeks diagnosed with PDA, admitted to the Neonatal Unit of the CHUSJ. Univariate comparative analysis was performed, and models for predicting the effectiveness of PDA treatment with ibuprofen were explored by multivariate logistic regression analysis.Results115 cases were included and 34 were excluded, with a final sample of 81 preterm infants with PDA. The univariate analysis revealed significant differences in the closure efficacy via medical treatment with ibuprofen in several variables, and a multivariate logistic regression model was obtained (discriminative capacity 72.2%, sensitivity 98.1%, specificity 57.1%), taking into account the effect of GA, type of delivery, need for diuretics treatment and platelet transfusion.ConclusionThis study enabled the population of preterm infants diagnosed with PDA to be characterized and the identification of a predictive model that can help predict the efficacy of medical treatment and thus contribute to optimizing the medical approach to the non-responders.     

Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age

Objectives

To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present.

Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults

ObjectiveTo compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD).Patients and methodsRetrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group — HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2 mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group — LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography.ResultsChanges on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1 year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p = 0.007 vs LDGH). No significant variations on echocardiographic parameters were observed.ConclusionThe HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen.     

Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals

IntroductionGoblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.MethodsMale BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale.ResultsInflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57 ± 1.30% for low dose; 1.50 ± 0.93% for high dose versus 12.93 ± 7.55%, P < 0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45 ± 0.30 for low dose; 0.81 ± 1.00 for high dose versus 2.85 ± 0.86 in the sensitized control group, P < 0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1 ± 0.43 versus 4.7 ± 0.96, P < 0.05 and 91.8 ± 47.7 versus 14.8 ± 4.6, P < 0.01, respectively).ConclusionVerapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.     

Platelet aggregation at discharge: A useful tool in acute coronary syndromes?

IntroductionInhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention.ObjectiveTo stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation.MethodsWe performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate^® analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0–188.0) days.ResultsThe median value of platelet aggregation was 16.0 U (11.0–22.5 U) with a maximum of 41.0 U and a minimum of 4.0 U (normal value according to the manufacturer: 53–122 U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5 U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A – platelet aggregation <18.5 U, n = 44; and group B – platelet aggregation ≥18.5 U, n = 26. The groups were similar with respect to demographic data (age 60.5 [49.0–65.0] vs. 62.0 [49.0–65.0] years, p = 0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p = 0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p < 0.01). Platelet aggregation higher than 18.5 U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38–32.90, p = 0.02).ConclusionIn our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.     

The relationship between oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crises

ObjectiveTo investigate the relationship between oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crises.MethodsA total of 73 patients with diabetic ketoacidosis and nonketotic hyperglycemia were treated on a low-dose insulin protocol using intravenous infusion of insulin with the established rate of 0.1 U·kg^? 1·h^? 1. The patients received intravenous fluids and nutrition orally and intravenously. The levels of serum ICAM-1, E-selectin, and 8-iso-prostaglandin F_2α (8-iso-PGF_2α); the activities of superoxide dismutase (SOD); the total antioxidant capacity (TAC) and the contents of malondialdehyde (MDA) in 68 patients with hyperglycemia crisis on admission and after insulin therapy with resolution of hyperglycemia and ketoacidosis (72 h after resolution) were measured. Another 33 healthy individuals served as normal controls.ResultsThe activities of SOD and TAC at admission were lower in patients with hyperglycemia crisis than in normal controls, and the levels of MDA, 8-iso-PGF_2α, ICAM-1 and E-selectin were higher in patients with hyperglycemia crisis than in normal controls (all p < 0.05). The activities of SOD and TAC in patients at resolution were significantly lower than in patients at admission and were significantly higher than in controls (p < 0.05). The levels of MDA, 8-iso-PGF_2α, ICAM-1 and E-selectin in patients at resolution were markedly lower than in patients at admission (all p < 0.05) and were significantly higher than in normal controls (p < 0.05). There was a significant positive correlation between ICAM-1 and SOD (r = 0.32, p < 0.05) and between E-selectin and MDA (r = 0.30, p < 0.05) in patients at admission, and the level of E-selectin was positively correlated with MDA and 8-iso-PGF_2α in patients at resolution (r = 0.33, 0.36, p < 0.05). In stepwise regression analysis, MDA and 8-iso-PGF_2α showed a significant association with E-selectin, and 8-iso-PGF_2α showed a significant association with ICAM-1.ConclusionThe oxidative stress and the levels of serum circulating adhesion molecules are significantly changed in patients with hyperglycemia crisis. Intensive insulin therapy can attenuate the abnormity of oxidative stress and the levels of serum circulating adhesion molecules in patients with hyperglycemia crisis.