Dynamic QT interval analysis in uraemic patients receiving chronic haemodialysis

OBJECTIVE: To analyse the duration of the QT interval and its relationship with heart rate changes in patients with uraemia, before and during haemodialysis. METHODS: QT and RR intervals were measured automatically using a dedicated algorithm with 24-h Holter recordings in 29 patients (15 women) receiving chronic haemodialysis. QT corrected for heart rate (QTc) and the slope of QT/RR linear regression were calculated. Arterial blood pressure (ABP) was measured before and during haemodialysis. Plasma concentrations of K+, Mg2+ and Ca2+ were assessed before and after haemodialysis. RESULTS: ABP decreased significantly from baseline (102.7 +/- 11.0 mmHg) during the first (100.6 +/- 8.8 mmHg, P < 0.05), second (95.6 +/- 10.6 mmHg, P < 0.05), and third (94.9 +/- 10.3 mmHg, P < 0.05) hours of haemodialysis. QTc was longer during haemodialysis than during a 4-h period of no dialysis (447 +/- 28 ms compared with 429 +/- 22 ms, P < 0.001), and increased progressively during haemodialysis, with the greatest value during the last hour of haemodialysis (454 +/- 32 ms compared with 426 +/- 22 ms, P < 0.001). QT/RR slopes and correlation coefficients were lower during haemodialysis than during the period of no dialysis (0.13 +/- 0.08 compared with 0.20 +/- 0.07, P < 0.001 and 0.48 +/- 0.30 compared with 0.81 +/- 0.20, respectively; P < 0.001), suggesting a reduced ability to adapt the QT interval in response to changes in heart rate. The effects of haemodialysis on QT interval and the QT/RR relationship were greater in women than in men. QTc variations during dialysis were not correlated with changes in ABP, but were inversely related to changes in Ca2+ concentration (r2 = 0.35; P = 0.001). CONCLUSIONS: In patients with uraemia, the haemodialysis session induces a progressive increase in QT interval and modifies its relationship with heart rate. These effects may predispose some individuals to ventricular arrhythmias at the end of and immediately after the haemodialysis session.     

Tacrolimus ointment in nickel sulphate-induced steroid-resistant allergic contact dermatitis.

Tacrolimus ointment is a topical immunomodulator. Currently, there is available evidence regarding the potential use of topical tacrolimus in a range of dermatological disorders. The aim of this study was to evaluate the efficacy and safety of tacrolimus ointment 0.1% for the nickel sulfate-induced steroid-resistant allergic contact dermatitis (ACD). A randomized, double-blind, placebo-controlled, parallel-group study design was performed in a total of 28 patients affected by nickel sulfate-induced steroid-resistant ACD after a 14-day run-in period. Then, the enrolled patients were randomized into two subgroups. Group A was treated with tacrolimus for 14 days and finally observed for a 7-day follow-up period. Group B, instead, was treated with placebo (vehicle). Four major symptoms (erythema, oozing, scaling, and itching) were considered as outcomes during the different phases of the study. In group A, during the treatment period with tacrolimus, a significant improvement was observed in all four considered symptoms. On the other hand, no improvement in symptoms was observed in the placebo-treated group B. Local adverse events in the tacrolimus-treated group, such as burning/itching at the application site, were transient and well tolerated. No patients withdrew because of burning/itching. In our study, tacrolimus ointment 0.1% appeared to be both effective and safe in the treatment of nickel sulfate-induced steroid-resistant ACD.     

Effect of bronchodilatation on single breath pulmonary uptake of carbon monoxide in chronic obstructive pulmonary disease

We studied 21 COPD patients in stable clinical conditions to evaluate whether changes in lung function induced by cumulative doses of salbutamol alter diffusing capacity for carbon monoxide (DL_CO), and whether this relates to the extent of emphysema as assessed by high resolution computed tomography (HRCT) quantitative analysis. Spirometry and DL_CO were measured before and after cumulative doses of inhaled salbutamol (from 200 μg to 1000 μg). Salbutamol caused significant increments of forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and flows at 30% of control FVC taken from both partial and maximal forced expiratory maneuvers. Functional residual capacity and residual volume were reduced, while total lung capacity did not change significantly. DL_CO increased progressively with the incremental doses of salbutamol, but this became significant only at the highest dose (1000 μg) and was independent of the extent of emphysema, as assessed by radiological parameters. No significant changes were observed in CO transfer factor (DLCO/VA) and alveolar volume (VA). The results suggest that changes in lung function induced by cumulative doses of inhaled salbutamol are associated with a slight but significant increase in DL_CO irrespective of the presence and extent of emphysema.     

ClC-5 Does Not Affect Megalin Expression and Function in the Thyroid.

Megalin is an endocytic receptor responsible for thyroglobulin (Tg) transcytosis, a process that favors hormone release. Accordingly, megalin KO mice have primary hypothyroidism. In the kidney, megalin expression is reduced when the gene encoding the chloride transporter ClC-5 is mutated. We investigated whether megalin expression and function in the thyroid are affected by ClC-5 using a ClC-5 KO mouse model. By Western blotting, ClC-5 was found in thyroid tissue extracts of WT, but not of ClC-5 KO mice. In addition, ClC-5 was found to be expressed by cultured thyroid cells (FRTL-5). The thyroid size, weight, and histology were similar in ClC- 5 KO and WT mice, as were the amounts of megalin in thyroid extracts. Accordingly, serum Tg, a measure of megalin-mediated transcytosis, was similar in WT and ClC-5 KO mice, suggesting that megalin function was unaffected. Thus, unlike in megalin KO mice, in ClC-5 KO mice thyroid function was unchanged, as indicated by the normal serum FT4 and TSH. We concluded that in the thyroid, unlike in the kidney, ClC-5 does not affect megalin expression and function, suggesting that megalin is differentially regulated in these two organs.     

Differential effect of agonistic anti-CD40 on human mature and immature dendritic cells: the Janus face of anti-CD40

Agonistic monoclonal antibodies to CD40 (CD40 mAbs) have a puzzling dual therapeutic effect in experimental animal models. CD40 mAbs induce tumor regression by potentiating antitumoral T-cell responses, yet they also have immunosuppressive activity in chronic autoimmune inflammatory processes. CD40 mAbs are thought to act on antigen presentation by dendritic cells (DCs) to T cells. DCs can be distinguished as either immature or mature by their phenotype and their ability to generate an effective T-cell response. Here we found that, on human cells, although anti-CD40 led immature DCs to mature and became immunogenic, it also reduced the capacity of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-alpha)-matured DCs to generate a specific CD4 T-cell response. This inhibitory effect was related to rapid and selective apoptosis of mature DCs. Anti-CD40-mediated apoptosis was due to an indirect mechanism involving cooperation with the death domain-associated receptor Fas, leading to activation of Fas-associated death domain protein (FADD) and caspase-8. On human cells, CD40 activation by such agonists could, therefore, trigger immune responses to antigens presented by immature DCs, which are otherwise nonimmunogenic, by inducing maturation. On the other hand, anti-CD40 mAbs, by rapidly inducing apoptosis, may reduce the capacity of inflammatory signal-matured immunogenic DCs to generate an effective T-cell response. These results call for caution in CD40 mAb-based immunotherapy strategies.     

Reduced apoptosis of CD8+ T-lymphocytes in the airways of smokers with mild/moderate COPD

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation in airways and lung parenchyma. CD8+ T-lymphocytes, crucial effector and regulatory cells in inflammation, are increased in the central and peripheral airways in COPD. The aim of this study was to assess the role of apoptosis in the accumulation of CD8+ T-lymphocytes within the airway wall in COPD. We examined the submucosa of transverse sections of central and peripheral airways from post-operative tissues from non-smokers (n?=?16), smokers with normal lung function (n?=?16), smokers with mild/moderate COPD (n?=?16), and smokers with severe/very severe COPD (n?=?9). TUNEL and immunohistochemistry techniques were used to identify apoptosis and cell phenotype, respectively. The percentage of apoptotic CD8+ T-lymphocytes was significantly lower (p?相似文献   

Alterations of atrial electrophysiology related to hemodialysis session: insights from a multiscale computer model

Background

The prevalence of atrial fibrillation is increased in patients with end-stage renal disease. Previous studies suggested that extracellular electrolyte alterations caused by hemodialysis (HD) therapy could be proarrhythmic.

Methods

Multiscale models were used for a consequent analysis of the effects of extracellular ion concentration changes on atrial electrophysiology. Simulations were based on measured electrolyte concentrations from patients with end-stage renal disease.

Results

Simulated conduction velocity and effective refractory period are decreased at the end of an HD session, with potassium having the strongest influence. P-wave is prolonged in patients undergoing HD therapy in the simulation as in measurements.

Conclusions

Electrolyte concentration alterations impact atrial electrophysiology from the action potential level to the P-wave and can be proarrhythmic, especially because of induced hypokalemia. Analysis of blood electrolytes enables patient-specific electrophysiology modeling. We are providing a tool to investigate atrial arrhythmias associated with HD therapy, which, in the future, can be used to prevent such complications.     

In systemic sclerosis macrovascular damage of hands digital arteries correlates with microvascular damage

Objective

To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by Color Doppler Ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls.

Methods

CDUS, NVC, Laser Doppler Perfusion Imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls.

Results

CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p < 0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvasculare damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings.

Conclusion

PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy.     

The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells

Objective

Obesity and cardiovascular disease recognize a common metabolic soil and may therefore share part of their genetic background. Genome-wide association studies have identified variability at the SH2B1 locus as a predictor of obesity. We investigated whether SNP rs4788102, which captures the entire SH2B1 variability, is associated with coronary artery disease (CAD) and/or myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM).

Design and setting

SNP rs4788102 was typed in 2015 White subjects with T2DM from three CAD case–control studies [n = 740 from the Gargano Hearth Study (GHS, Italy); n = 818 from the Joslin Hearth Study (JHS, Boston); n = 457 from the University of Catanzaro (CZ, Italy)].

Results

SNP rs4788102 (G/A) was not associated with CAD (overall allelic OR = 1.06, 95% CI = 0.93–1.21; p = 0.37). On the contrary, it was associated with MI in GHS (1.42, 1.12–1.81; p = 0.004) and in the three samples analyzed together (1.21, 1.04–1.41; p = 0.016). Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n = 4, p = 0.03) but not the G/A (n = 5, p = 0.83) genotype. Of the SNPs in perfect LD with rs4788102, one (rs7498665) affects amino acid polarity (Ala484Thr) and falls into a highly conserved protein segment of SH2B1 containing a class II SH3 domain binding site.

Conclusions

Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells. Further studies are needed to replicate this association and dissect the biology underlying this finding.     

Cardiac event recorder yields more diagnoses than 24-hour Holter monitoring in patients with palpitations]

BACKGROUND: Palpitations are a common symptom that sometimes results from a substantial cardiac arrhythmia. A 24-hour Holter monitoring is usually used, but the yield of this instrument is low in patients whose symptoms occur infrequently. The aim of this study was to compare the diagnostic yield and the cost-effectiveness of transtelephonic event recorder (TER) with those of Holter monitoring in patients with intermittent palpitations. METHODS: Three hundred and ten patients with intermittent palpitations were allocated to the study and randomly assigned to receive a TER or 24-hour Holter monitoring. TER was given to patients until recording was obtained while symptoms occurred or was used at most for 7 days. At enrollment, a basal trace was recorded. Patients with palpitations recorded the one lead ECG trace and sent it by phone (fixed or mobile) to the telemedicine call center where a trained nurse compared the trace with the basal one and checked the patient's symptoms. The cardiologist reported "on-line" all the traces sent in the presence of an arrhythmic event and "stored and forwarded" all the other traces. Standard methods were used for Holter recording and reading. RESULTS: Patients with palpitations during the examination were 119 (76.8%) in the group of TER and 74 (47.8%) in the Holter group (p < 0.000) with an efficacy increase of 29% for TER. In symptomatic patients there were no differences between the two groups about the presence or absence of arrhythmias checked in the ECG traces; the time necessary to make a presence/absence diagnosis of arrhythmias was 2.97 +/- 2.74 days with the event recorder. The total cost of 155 tests made with Holter was altogether 9605.35 Euro (costs per test 61.97 Euro), while the one of TER was 6019.2 Euro (cost par test 38.83 Euro). The cost-effectiveness analysis was 129.80 Euro for Holter and 50.57 Euro for TER, with a saving of 79.23 Euro for every diagnosis made. CONCLUSIONS: TER allows to detect intermittent palpitations in real time; it is more useful and effective than Holter; moreover this effectiveness was also confirmed by the cost analysis in which TER resulted less expensive.