Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Intravenous dexmedetomidine for treatment of intraoperative penile erection

Background  

Intraoperative penile erections following the initiation of either regional or general anaesthesia is rare; however, when it occurs in patients undergoing urologic procedures it may delay, or even cancel the planned surgery. The aetiology is unclear. Various treatments proposed for producing detumescence are not always effective. Use of intracavernous alpha-adrenergic agonists is an efficient and rapid but short-lasting treatment. Furthermore, repeated intracavernous injections of vasoactive drugs may be harmful. Dexmedetomidine is a potent, selective α₂-adrenoreceptor agonist. In our study, we evaluated the effect of dexmedetomidine on intraoperative penile erection.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

The relationship of serum erythropoietin level with coronary collateral grade

Background

Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade.

Methods

Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II.

Results

The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals.

Conclusions

Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.     

Poor coronary collateral circulation is associated with higher concentrations of soluble adhesion molecules in patients with single-vessel disease

OBJECTIVE: As the endothelium and inflammatory cells play a crucial role in the development of collaterals after a sudden or slowly progressing stenosis of coronary arteries, the levels of soluble endothelial adhesion molecules (CAMs) including vascular cell adhesion molecule (VCAM-1) intercellular adhesion molecule-1 (ICAM-1) and E-selectin were compared between patients with poor coronary collaterals and patients with well-developed collaterals. METHODS: In the study, 97 non-diabetic subjects with single-vessel disease were included. Collateral supply to the stenotic coronary artery was determined by angiographic grading system of 0-3 (Rentrop et al. J Am Coll Cardiol 1985; 5:587-592). Serum levels of adhesion molecules were measured by enzyme-linked immunosorbent assay. RESULTS: Patients were divided into two groups according to the collateral degree (group A: 50 patients with grade 0 and 1; group B: 47 patients with grade 2 and 3 collaterals). The groups were well matched with respect to baseline clinical and angiographic characteristics. Levels of soluble VCAM-1 (mean+/-SEM; 875+/-26.6 versus 742.7+/-35.1 ng/ml; P=0.004), ICAM-1 (322.4+/-12.4 versus 269.4+/-13.3 ng/ml; P=0.005), and E-selectin (43.6+/-2.6 versus 33+/-2.4 ng/ml; P=0.004) were found to be significantly higher in group A in comparison with group B. In addition, when patients were divided into four groups according to the collateral degree, patients with grade 0 collaterals had the highest values and those with grade 3 collaterals had the lowest values for all these molecules. CONCLUSIONS: We concluded that poor collateral circulation is associated with increased levels of soluble CAMs in patients with obstructive coronary artery disease. However, further studies are needed to elucidate the exact role of these inflammatory markers in the setting of poor collateral circulation.     

The effects of antioxidants on exercise-induced lipid peroxidation in patients with COPD

OBJEctive: The oxidant-antioxidant balance plays an important role in the pathogenesis of COPD. The aim of the present study was to evaluate the effects of exercise, as an oxidative stress factor on the oxidant-antioxidant balance and to investigate whether short-term antioxidant treatment affects lipid peroxidation products. METHODOLOGY: Twenty-one stable COPD patients and 10 control subjects were included in the study. Symptom-limited exercise tests were performed by all subjects. Blood was collected before and 1 h after exercise in control subjects and before, 1 and 3 h after exercise in COPD patients, for analysis of malondialdehyde (MDA), reduced glutathione (GSH) and vitamin E (VE) levels. VE and vitamin C treatments were added to the regular bronchodilator therapy in 10 COPD patients for 1 month. After the treatment period, an exercise test was performed and blood was collected again for MDA, GSH and VE levels. RESULTS: Baseline GSH and VE levels were significantly lower in the COPD group when compared with the control subjects. There was no statistically significant difference in MDA levels between the two groups. In the COPD group, MDA levels 3 h after exercise were significantly higher than at baseline. In contrast there were no significant differences in MDA, VE and GSH levels in the control group after exercise. VE and MDA levels increased significantly after exercise in COPD patients but there was no difference in GSH levels. Baseline exercise time was significantly lower in the COPD group than in the controls. In 10 COPD patients who were given antioxidant therapy, their exercise time increased significantly and there was no increase in MDA and VE levels after the repeated exercise test. CONCLUSIONS: Antioxidant levels were significantly lower in COPD patients than in control subjects. In these patients, exercise results in more significant oxidative stress and lipid peroxidation than in control subjects and antioxidant therapy may decrease lipid peroxidation following exercise and improve exercise capacity.     

应用非甾体抗炎药对高血压合并冠状动脉疾病患者的有害作用

慢性疼痛综合征患者常应用非甾体抗炎药( non-steroidal anti-inflammatory drugs,NSAID).许多这类患者有潜在的高血压和冠状动脉疾病.临床试验和系统性分析显示,选择性环氧化酶2抑制剂增加心肌梗死的风险[J].该发现可能导致更普遍地应用非选择性NSAID作为治疗慢性疼痛综合征的替代手...     

The effects of levofloxacin on ECG parameters and late potentials

In this study, our aim was to investigate the proarrhythmic effects of levofloxacin. Twenty-six patients who were diagnosed as having community-acquired pneumonia were enrolled in the study. Intravenous levofloxacin, 500 mg daily, was given, and 12-lead ECG measurements were obtained before the infusion, at 30 and 60 minutes during infusion, and 10 minutes after its cessation. Resting late potentials were recorded before and after infusion. Twelve female and 14 male patients were participated the study. Mean age was 51.3 +/- 22.3 years. Levofloxacin infusion increased the heart rate (HR) and prolonged the corrected QT (QTc) intervals significantly (baseline HR: 84.6 +/- 18.8 vs. HR at 60 minutes: 88.6 +/- 18, P = 0.02; baseline QTc: 413.5 +/- 36.9 milliseconds vs. QTc at 60 minutes: 426.1 +/- 34.7, P = 0,006). There was no significant difference between the late potential values obtained before and after infusion. None of our patients experienced severe arrhythmia that required stopping the treatment. A single dose of IV levofloxacin prolongs the QTc interval without significant change in late potentials. Monitoring ECG during levofloxacin infusion might be necessary in patients who have a condition that could affect the QTc interval.