Effects of autonomic dysfunction on exercise tolerance in systemic sclerosis patients without clinical and instrumental evidence of cardiac and pulmonary involvement.

OBJECTIVES: Autonomic dysfunction (AD) in systemic sclerosis (SSc) was already confirmed through heart rate variability (HRV) analysis. Cardio-pulmonary exercise testing (CPET) is a useful tool in early detection of exercise tolerance in SSc patients. Aim of the study was to assess the relationships existing between AD and exercise tolerance. METHODS: Thirty-two [4 M, 28 F; median age: 47.5 (20-65) years] consecutive SSc patients were enrolled. All patients underwent pulmonary function testing, incremental symptom-limited CPET and twenty-four hours ECG Holter recording with HRV analysis in time and frequency domain. Multiple regression analysis was performed in order to identify independent HRV predictors of exercise tolerance and cardiac efficiency during the effort. RESULTS: HRV analysis showed significant differences in power in low and high frequency (LF and HF, respectively) and their ratio (LF/HF) compared to healthy controls. Nocturnal ratio be- tween power in low and high frequency at HRV (LF/HFnight) was shown to be the only independent positive predictor of maximal work load (R2=18.6%, p=0.014) and maximal oxygen consumption (V' O2 peak) expressed both as absolute value (R2=24.2%, p=0.004) and as corrected for body weight (R2=21.6%, p=0.007). A positive linear relationship was also found between nocturnal LF (LFnight) and the oxygen uptake/work rate (V'O2/W) slope (R2=15.8%, p=0.024). CONCLUSIONS: In SSc patients without cardiopulmonary involvement AD is associated with better exercise tolerance and cardiac function during physical effort. Further studies are needed to confirm these results.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V'O2max), and O2 uptake at lactic acid threshold (V'O2@LT). RESULTS: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V'O2max, V'O2max/Kg and V'O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V'O2@LT, V'O2 @LT%, V'O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

Lack of the QTc physiologic decrease during cardiac stress test in patients with type 2 diabetes treated with secretagogues.

Patients with type 2 diabetes are at increased susceptibility to a prolonged QT interval. Furthermore, insulin secretagogues, drugs used to treat diabetes, may prolong QT interval and provoke arrhythmias. We evaluated whether secretagogues can affect QTc interval during cardiac stress test in 20 patients with type 2 diabetes treated with secretagogues. ECG stress test was performed in all patients. QTc interval was calculated both before cardiac stress test (BCST) and at acme of cardiac stress test (ACST). Diabetic patients treated with secretagogues showed longer QTc-ACST values than those treated with metformin only. QTc-ACST values resulted shorter than QTc-BCST values in control group. Diabetic patients treated with secretagogues showed QTc-ACST values significantly longer than QTc-BCST values. In our study, diabetic patients treated with secretagogues did not show the QTc physiologic decrease that is a protective against arrhythmias. These results suggest to evaluate, in these patients, QT length, even during routine cardiac stress test.

Transaminase levels in the upper normal range are associated with oral hypoglycemic drug therapy failure in patients with type 2 diabetes.

Incident diabetes and the worsening of diabetes have recently been linked to hepatic steatosis. Aim of our study was to determine whether oral hypoglycemic agent failure is associated with higher transaminase levels (valid measure of liver steatosis). We selected 200 patients, attenders (3 consecutive annual evaluations) in our clinic, with type 2 diabetes among which 100 with oral hypoglycemic agents failure and 100 who were still responsive to oral therapy. Failure to therapy was defined as glycated hemoglobin >7.5% despite maximal-dose oral therapy. We analyzed patient histories and laboratory data. Compared with oral-therapy-responsive patients, those with failure had a significantly higher level mostly of alanine aminotransferase at the time of therapy failure and 2 years before. They were more likely to have had symptoms of hyperglycemia at the time of diabetes diagnosis. Regression analysis indicated that each 5-unit increase in transaminase levels independently increased the risk for oral hypoglycemic agents failure by 1.70. Higher liver transaminase levels, especially in patients who had symptomatic hyperglycemia at diabetes diagnosis, associate with oral hypoglycemic agent failure. The possible pathogenetic link between transaminase and declining islet function might consist of insulin resistance and increased circulating fatty acid levels, in turn causing liver steatosis and beta-cell dysfunction.

PFAPA syndrome in a young adult with a history of tonsillectomy.

Since its clinical definition in 1987, the syndrome called, "periodic fever, aphtous stomatitis, pharyngitis and cervical adenitis" syndrome (PFAPA) has been considered peculiar to pediatric age. In the recent literature there are a few case reports of PFAPA in adults. We describe a case of a 21-year-old female affected by PFAPA who presented a history of tonsillectomy at the age of four. To our knowledge this is the fourth case described with a diagnosis of PFAPA in an adult with a history of tonsillectomy during childhood. Although the role of tonsillectomy in the treatment of PFAPA is still controversial, due to the lack of definitive data in literature, this case suggests that fever episodes may relapse several years after surgery.

Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes.

AIM: Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular events in these patients. The benefits of statin therapy cannot be explained only by the lipid-lowering effect. The aim of this study was to test the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear factor-kappaB (NFkappaB) levels and markers of inflammation (C-reactive protein, CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from diabetic patients. METHODS: Twenty-two type 2 diabetic patients were treated for 8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood sample was collected for measurement of glucose, lipid profile (total cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c), CRP and for isolation of monocytes. RESULTS: Atorvastatin decreased total (p<0.0001) and LDL (p<0.01), and incresased HDL choles-terol (p<0.02). CD36 surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was reduced in circulating monocytes after atorvastatin therapy (p<0.02) while immunoblot analysis showed reduced nuclear and increased cytoplasm NFkappaB levels (p<0.05). Finally, TNFalpha production in lipopolysaccharide-activated monocytes from patients treated with atorvastatin was reduced (p<0.05). CONCLUSION: These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.

Electro-optic and electro-absorption characterization of InAs quantum dot waveguides.

Optical properties of multilayer InAs quantum dot waveguides, grown by molecular beam epitaxy, have been studied under applied electric field. Fabry-Perot measurements at 1515 nm on InAs/GaAs quantum dot structures yield a significantly enhanced linear electro-optic efficiency compared to bulk GaAs. Electro-absorption measurements at 1300 nm showed increased absorption with applied field accompanied with red shift of the spectra. Spectral shifts of up to 21% under 18 Volt bias was observed at 1320 nm.