Bowel preparation with polyethylene glycol electrolyte solution: optimizing the splitting regimen

AimQuality of bowel cleansing significantly increases the shorter the time between bowel solution intake and endoscopic examination. We tested the efficacy and patient tolerability following a modified polyethylene glycol electrolyte (PEG) splitting regimen.MethodsThis was a prospective, single-blind, randomized, study. Patients were assigned to receive either PEG 4 L the afternoon before colonoscopy or PEG 3 L the day before and 1 L 3 h before the procedure the day of colonoscopy.ResultsThe study population consisted of 336 patients, including 168 participants in each study arm. Although the bowel preparation quality was similarly quoted as excellent/good following the split and full regimen (95.2% vs 92.8%; p = 0.3), a significant (p < 0.0001) shift from good towards an excellent preparation (26.8% vs 68.4%) was observed following the split regimen as compared to the full regimen (55.4% vs 37.5%). The incidence of side-effects did not differ. When patients were asked about a future preparation if needed, 69% and 31% following the split and full regimen, respectively, declared to accept again the same preparation, the difference being statistically significant (p < 0.001).ConclusionsOur data found that an excellent bowel cleansing could be frequently achieved by simply modifying the split regimen from the standard PEG 2 plus 2 L to 3 plus 1 L.     

Impact of dyslipidaemia on arterial structure and function in urban indigenous Australians

BackgroundPremature cardiovascular disease (CDV) is highly prevalent in urban Indigenous Australians. We studied arterial structure and function in 144 volunteers aged 15–66 years to assess the role of dyslipidaemia and other traditional vascular risk factors on cardiovascular risk in young and older urban Indigenous Australians.MethodsWe assessed carotid intima-media thickness (CIMT) by high-resolution B-mode ultrasound imaging of the common carotid artery and peripheral wave reflection using applanation tonometry to obtain the aortic augmentation index (AI) in Indigenous Australian participants of the Darwin Region Urban Indigenous Diabetes (DRUID) study.ResultsParticipants aged 15–24 years demonstrated fewer cardiovascular risk factors than the older group (25–66 years) and predictors of CIMT and AI differed between younger and older groups. CIMT was higher in the older group (0.67 mm vs. 0.61 mm, p = 0.004) and in those with diabetes (0.81 mm vs. 0.67 mm, p < 0.001). AI was higher in the older group (24% vs. 0%, p < 0.001), but was not affected by diabetes status. On multivariate regression analysis, low HDL-cholesterol was the only independent predictor of CIMT in the younger group; triglycerides, heart rate (inverse) and height (inverse) were independent predictors of AI in the same group.ConclusionDyslipidaemia (low HDL-cholesterol or elevated triglycerides) is independently associated with non-invasive measures of cardiovascular disease in a relatively healthy and young subgroup of this high-risk population. We propose that triglycerides and low HDL-cholesterol may represent the most useful commonly measured clinical indicators of cardiovascular risk in young, urban Indigenous Australians.     

Feasibility of laparoscopic restorative proctocolectomy without diverting stoma

AimRestorative proctocolectomy performed before the advent of laparoscopy had evolved to frequently omit a diverting stoma. Our aim was to assess the impact of a diverting stoma on postoperative outcomes following laparoscopic restorative proctocolectomy.MethodData on all patients undergoing a laparoscopic restorative proctocolectomy at our institution were prospectively collated in a database.ResultsBetween November 2004 and February 2010, 71 patients (38 females) underwent laparoscopic restorative proctocolectomy. Indications included familial adenomatous polyposis (n = 34), ulcerative colitis (n = 35), indeterminate colitis (n = 1) and Lynch syndrome (n = 1). Laparoscopic restorative proctocolectomy was performed as a one-stage procedure in 49 patients, and after a sub-total colectomy in 22. Seven patients in each group underwent the formation of a diverting stoma. Nine patients required conversion to open surgery. Sixteen patients experienced at least one postoperative complication. The postoperative morbidity was 29% (n = 4/14) and 21% (n = 12/21) in patients with and without a stoma (p = 0.8), and the rate of fistula was 21% and 5%, respectively (p = 0.08). Seven percent of patients with a stoma and 16% without stoma had an intra-abdominal collection (p = 0.7). Nine patients required reoperation. The reoperation rate was not influenced by the presence or absence of a diverting stoma.ConclusionLaparoscopic restorative proctocolectomy can be performed safely without a diverting stoma in selected patients.     

Relationship between serum levels of osteocalcin and atherosclerotic disease in type 2 diabetes

AimsTo analyze the relationship between serum levels of osteocalcin and parameters of atherosclerosis in patients with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study of 78 patients with T2DM evaluated intima–media thickness, and the prevalence of coronary heart disease, atherosclerotic plaques and aortic calcifications. Serum osteocalcin levels were also determined by radioimmunoassay.ResultsThe patients’ mean age was 57.8 ± 6.4 years (duration of diabetes: 13.4 years; mean HbA_1c level: 8.01%), and 37.2% had coronary heart disease, 56% had an abnormal intima–media thickness, 26.9% had carotid plaques and 32.1% had aortic calcifications. Coronary heart disease was associated with higher levels of osteocalcin in male vs female patients (1.95 ± 1.36 vs 0.93 ± 0.86 ng/mL, respectively; P = 0.006). Also, higher concentrations of osteocalcin were found in female patients with vs without abnormal intima–media thicknesses (2.17 ± 1.84 vs 1.25 ± 0.67 ng/mL, respectively; P = 0.042), carotid plaques (2.86 ± 2.10 vs 1.43 ± 1.09 ng/mL, respectively; P = 0.03) and aortic calcifications (2.85 ± 1.97 vs 1.26 ± 0.83 ng/mL, respectively; P = 0.002). Serum osteocalcin levels were associated with coronary heart disease on multivariate logistic regression (odds ratio: 2.27, 95% confidence interval: 1.21–4.25; P = 0.01).ConclusionIn T2DM patients, serum osteocalcin levels were associated with parameters of atherosclerosis, suggesting that osteocalcin is involved not only in bone metabolism, but also in atherosclerotic disease.     

In vivo impact of prodrug isosorbide-5-nicotinate-2-aspirinate on lipids and prostaglandin D2: Is this a new immediate-release therapeutic option for niacin?

ObjectivesTo evaluate the pharmacokinetics and effects of the first immediate-release (IR) niacin–aspirin prodrug (ST0702) on lipid, prostaglandin and thromboxane levels in non-human primates (NHPs).MethodsWe compared 28 mg/kg crystalline IR niacin, equimolar doses of crystalline IR ST0702 and control on low density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and triglycerides (Tg) in NHPs (6 per group) over 48 h (daily oral gavage). In addition, we compared IR niacin and ST0702 effects on prostaglandin (PG)D₂, ex vivo thromboxane B₂ (TXB₂) levels and plasma pharmacokinetics.ResultsST0702 is metabolised in vivo to aspirin, niacin and salicylic acid with T_max values of 30, 45 and 95 min respectively using a non-compartmental model. ST0702 resulted in 38% and 40% reductions in LDL-C and ApoB levels compared to control over the 48 h period (p = 0.027 and p = 0.012 respectively). Corresponding values were 32% and 25% for niacin (both p = NS vs control). ST0702, but not niacin, decreased Tg levels (p = 0.017 for between group difference). Post prandial glycaemia was attenuated vs baseline in the ST0702 group only. Ex vivo serum TXB₂ generation was suppressed at 15 min and complete suppression of TXB₂ was sustained at 24 h (p < 0.01 vs niacin). ST0702 suppressed PGD₂ exposure eightfold (p = 0.012) compared to niacin over the first 24 h.ConclusionsThis two-dose study in NHPs suggests that ST0702 is more effective than IR niacin on lipid profiles, while suppressing TXB₂ and PGD₂ increases and prevents post-prandial glycaemia. ST0702 shows promise as a new IR therapeutic option for niacin.     

Association of single measurement of estimated glomerular filtration rate and non-quantitative dipstick proteinuria with all-cause and cardiovascular mortality in the elderly. Results from the Progetto Veneto Anziani (Pro.V.A.) Study

ObjectiveTo explore the independent and combined clinical validity of estimated glomerular filtration rate (eGFR) and proteinuria on predicting all-cause and cardiovascular mortality in an Italian elderly population.MethodsBaseline eGFR and proteinuria, all-cause and cardiovascular mortality during a mean follow-up time of 4.4 years were evaluated in 3063 subjects aged 65 years and older of the Progetto Veneto Anziani (Pro.V.A.) Study.ResultsSubjects with eGFR < 60 ml/min/1.73 m² (n = 956) presented a higher prevalence of proteinuria in comparison with those with eGFR ≥ 60 ml/min/1.73 m² (33.8% vs 25.1%, p < 0.01). After multivariable adjustment including proteinuria and major diseases, eGFR < 60 ml/min/1.73 m² was not associated with increased all-cause mortality. After multivariable adjustment including eGFR and major diseases, proteinuria was associated with all-cause mortality in overall subjects (HR = 1.43, 95% CI 1.15–1.78, p < 0.01), and in both sexes. After multivariable adjustment both eGFR < 60 ml/min/1.73 m² (HR = 1.68, 95% CI 1.02–2.78, p = 0.04), and proteinuria (HR = 2.07, 95% CI 1.31–3.27, p < 0.01) were associated with increased cardiovascular mortality. Subjects with both impaired eGFR and presence of proteinuria showed a higher risk for both all-cause and cardiovascular mortality compared to those with normal eGFR and absence of proteinuria.ConclusionIn this general Italian elderly population proteinuria is an independent predictor of all-cause and cardiovascular mortality, while eGFR is not an independent predictor of all-cause mortality, and it is nominally significantly associated with cardiovascular mortality. However, mortality risk is higher in individuals with combined reduced eGFR and proteinuria.     

Single-port versus multiport laparoscopic ileocecal resection for Crohn's disease

Background and AimsSeveral case series have demonstrated the feasibility of single-port laparoscopic ileocecal resection in Crohn's disease. However, only a few studies compared the single-port with a multiport laparoscopic ileocecal approach. The aim of this study was to compare short term surgical outcome parameters between single-port and multiport laparoscopic ileocecal resections for Crohn's disease.MethodsTwenty-one patients who underwent single-port laparoscopic ileocecal resection between March 2010 and September 2012 were prospectively registered. A matched comparison on a 1:2 basis was performed with patients who underwent multiport laparoscopic ileocecal resection from January 1999 to March 2010. Matching parameters were BMI, length of diseased bowel resected and the presence of fistulas. Endpoints were the length of postoperative hospital stay, operative time, conversions, complications, postoperative pain scores and postoperative analgesia consumption.ResultsTwenty-one patients undergoing single-port resection were matched to 42 patients undergoing multiport resection. The postoperative stay (4 days, iqr 4–5 vs. 5 days, iqr 4–6; p = 0.033), operative time (103 min, iqr 94.0–121.0 vs. 123.5 min, iqr 100.0–157.0; p = 0.036) and morphine use on the first postoperative day (12.5 mg, iqr 5.0–33.3 vs. 28 mg, 15.0–50.0; p = 0.012) differed significantly. Postoperative pain scores and complications were similar in both groups. This study was limited by potential selection bias.ConclusionsSingle-port laparoscopic ileocecal resection is safe and feasible in Crohn's disease and is associated with less need for pain medication postoperatively as opposed to multiport laparoscopic ileocecal resection.     

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model

BackgroundThe impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury.MethodsPES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10^?6 M acetylcholine for 2.5 min, and intracoronary bolus of 100 μg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries (n = 25 PES and n = 25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall.ResultsIn spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness (p < 0.001) and reflexion index (p < 0.001) were significantly higher and the distensibility index (p < 0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index (p < 0.001) and the distensibility index (p < 0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization (r = 0.617, p < 0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score (r = 0.646, p < 0.001), vessel wall inflammation (r = 0.657, p < 0.001) and medial thickening (r = 0.672, p < 0.001) correlated significantly with the endothelium-independent stiffness index.ConclusionsImplantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.     

Pulmonary function at peak exercise in patients with chronic heart failure

BackgroundVarious respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients.Materials and methodsSeventy seven (66 male/11 female) patients with clinical stable CHF (age: 52 ± 11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET.ResultsPercent predicted forced expiratory volume in 1 s (FEV₁) was 91 ± 12, %predicted forced vital capacity (FVC) was 92 ± 13, %FEV₁/FVC was 81 ± 4, and %predicted IC was 85 ± 18. Peak exercise IC was lower than resting (2.4 ± 0.6 vs. 2.6 ± 0.6 l, p < 0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p < 0.001), V_E/V_CO2slope (p < 0.001), resting Pimax (p = 0.005) and post-exercise Pimax(p < 0.001). At rest, there was a statistically significant difference in end-tidal CO₂ (P_etco2) (p = 0.002), in breathing frequency (p = 0.004), in inspiratory time (Ti) (p = 0.04) and in total respiratory time (T_Tot) (p = 0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (V_E) (p < 0.001), tidal volume (V_T) (p < 0.001), respiratory cycle (V_T/T_I) (p < 0.001) and P_etco2(p < 0.001).Peak IC was correlated with peak V_O2 (r = 0.72, p < 0.001), anaerobic threshold (r = 0.71, p < 0.001), V_O2/t slope (r = 0.54, p < 0.0001), and post-exercise Pimax (r = 0.62, p < 0.001).ConclusionsIn patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.     

Urine α-Glutathione S-transferase, systemic inflammation and arterial function in juvenile type 1 diabetes

BackgroundDespite marked improvement in therapy and monitoring of patients with insulin-dependent (type 1) diabetes, diabetic nephropathy remains a serious complication, with subsequent end-stage renal disease in about 20% of cases.ObjectiveTo investigate in young patients with type 1 diabetes whether urine α-Glutathione S-transferase to creatinine ratio (α-GST:crea) relates to markers of systemic inflammation and subclinical vasculopathy.DesignChildren and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type 1 diabetes screened in a previous study for proximal tubular (urine α-GST:crea ratio) and renal (plasma creatinine, cystatin C glomerular filtration rate (GFR), and timed urine albumin excretion rate (AER)) function were, within the same timeframe, also investigated for vascular (blood pressure, carotid artery intima–media thickness (IMT) and compliance (CAC), brachial artery flow-mediated dilatation (FMD) and plasma cyclic guanosine monophosphate (cGMP) and inflammatory (C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α)) profiles. Exposure to environmental tobacco smoke (ETS) was assessed through questionnaire (n = 67 respondents).ResultsNone of the patients (n = 69) had overt renal insufficiency. AER correlated with age (p = 0.01, r = 0.3), diabetes duration (p = 0.02, r = 0.3), FMD (p = 0.04, r = ? 0.3, n = 52), CAC (p = 0.03, r = ? 0.3, n = 62) and cGMP (p = 0.01, r = ? 0.3, n = 59). α-GST:crea was lower (p = 0.03) in patients than in controls. α-GST:crea appeared to be particularly lower in older patients (p = 0.004, r = ? 0.34 vs age), in those with worse diabetic control (p = 0.03, r = ? 0.26 vs HbA1c), and in those with lower carotid artery elasticity (p = 0.017, r = 0.3 vs CAC). Although ETS had no direct significant impact on α-GST:crea, α-GST:crea correlated with FMD only in patients with ETS (r = 0.5, p = 0.009, n = 13). α-GST:crea showed positive association with TNF-α (p = 0.01, r = 0.3).ConclusionIn children and adolescents with type 1 diabetes, lower levels of urine excretion of α-GST:crea appear to be associated with decreasing elasticity and endothelial vasomotor function of peripheral arteries, especially in patients with ETS. In contrast, higher levels of α-GST:crea are more common in patients with elevated markers of systemic inflammation. Large scale prospective studies are needed to clarify the meaning and mechanisms of this association.     

Serum vascular endothelial growth factor in cyanotic congenital heart disease functionally contributes to endothelial cell kinetics in vitro

BackgroundRemarkable amounts of neovascularization develop in patients with cyanotic congenital heart disease who have low pulmonary blood flow and systemic cyanosis, but the factors functionally responsible for angiogenesis in cyanotic congenital heart disease have not been determined.Methods and resultsTo investigate the functional angiogenic molecules in serum from these patients, serum angiogenic activity was studied in 21 patients (systemic oxygen saturation: 82 ± 1.9%) and in 17 healthy controls. Patient serum was more active in stimulating the tube formation of human umbilical vein endothelial cells (HUVECs) into capillary-like structures than control serum (150% vs 104% of internal control; p < 0.001). This increased serum angiogenic activity normalized after total cardiac repair (p < 0.001). The migration activity of HUVECs was also accelerated in patient serum (p = 0.007). To identify the molecules in patient serum affecting tube formation of HUVECs, we examined the effects of an inhibitor or a neutralizing antibody against various angiogenic molecules on in vitro angiogenesis. Both the soluble vascular endothelial growth factor (VEGF) receptor 1 and the VEGF receptor 2 tyrosine kinase inhibitor SU5416 reduced the basal serum angiogenic activity of patients and this was reversed by a supplement of recombinant human VEGF.ConclusionOur results indicate that serum VEGF functionally contributes to vascular endothelial cell kinetics in patients with cyanotic congenital heart disease.     

eGFR and creatinine clearance in relation to metabolic changes in an unselected patient population

BackgroundIt is widely assumed that moderate to severe renal failure (creatinine clearance < 60 ml/min; or an MDRD-4 (Modification of Diet in Renal Disease equation) < 60 ml/min/1.73 m²) is associated with metabolic changes, often needing further assessment and treatment. We investigated whether such abnormalities are already present at earlier stages of kidney disease, as assessed by 24-hour urine sampling and MDRD-4 calculation.MethodsA select, retrospective cohort study was conducted. Creatinine clearance was measured by collecting 24-hour urines. The individual eGFRs were calculated with the MDRD-4 formula and patients were then divided by renal function category (< 15, 15–30, 30–45, 45–60, 60–90, > 90 ml/min(/1.73 m²)). Per clearance category the number of people with anaemia, hypokalaemia, uraemia and hyperphosphataemia was evaluated.ResultsThe median creatinine clearance rate was 67.3 ml/min (quartiles: 42.9–95.8) versus a median MDRD-4-eGFR of 51.6 ml/min/1.73 m² (35.8–67.7). Anaemia, hyperkalaemia, hypocalcaemia, and uraemia were found to be present at higher levels of creatinine clearance rate and eGFR than previously reported (p < 0.0005). This increased prevalence was more pronounced in elderly subjects, particularly with respect to anaemia (OR 2.71 and 2.02 for MDRD-4 and creatinine clearance respectively, p < 0.0005). The same holds for the proportion with uraemia (OR 1.85, p < 0.0005) and hypocalcaemia (OR 1.97, p = 0.011) for MDRD-4.ConclusionMetabolic changes in an in- and outpatient hospital population are present at earlier stages than was stated in recent guidelines, especially when creatinine clearance levels are used as indicators. This might have implications for testing and treatment of patients with suspected kidney disease and/or loss of renal function.     

Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis

ObjectivesThe soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.MethodsA cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.ResultsPlasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p = 0.007) and IL-6 (p = 0.002), whereas sRAGE was negatively associated with those inflammatory markers (p = 0.001, p = 0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β = ?0.230, p = 0.037, β = 0.155, p = 0.045) and VCS (β = ?0.205, p = 0.049, β = 0.197, p = 0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03–1.25, p = 0.009), presence of diabetes (OR 13.4, 95% CI: 1.20–150.18, p = 0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05–5.11, p = 0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT > 1.0 mm and/or plaque formation).ConclusionsOur findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.     

Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism

BackgroundThe relationship between ischemia-modified albumin (IMA) and thyroid dysfunction remains uncertain. This study aimed to investigate the influence of overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on serum IMA levels.MethodsA total of 35 untreated patients with Ohe, 35 untreated patients with Oho, and 35 control subjects were enrolled in the study. C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were measured and evaluated before and after treatment.ResultsCRP, Hcy, and IMA levels and lipid profiles were higher in patients with Oho than in euthyroid or Ohe subjects (p < 0.05). Basal IMA levels were reduced after treatments in all patients (p < 0.05). In Ohe patients, serum IMA levels were positively correlated with free triiodothyronine (r = 0.424, p = 0.011) and free thyroxine (r = 0.567, p < 0.001) levels. In Oho patients, serum IMA levels were inversely correlated with free triiodothyronine (r = ? 0.555, p = 0.001) and free thyroxine (r = ? 0.457, p = 0.006) but positively correlated with anti-thyroid peroxidase antibody, C-reactive protein, and homocysteine levels (p < 0.05). Linear regression analyses showed that free triiodothyronine was the most important factor affecting serum IMA levels in Ohe (β = 0.694, p = 0.019) and in Oho (β = ? 0.512, p = 0.025).ConclusionsIMA levels are increased in patients with thyroid dysfunction, particularly in overt hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative stress status.     

Correlates of endothelial function and the peak systolic blood pressure response to a graded maximal exercise test

PurposeAn elevated systolic blood pressure (SBP) response to a graded maximal exercise stress test (GEST) may be a predictor of endothelial dysfunction and hypertension. We examined relationships among the GEST peak SBP response and indicators of endothelial function.MethodsMen (n = 48, 43.7 ± 1.4 yr) with high BP (145.1 ± 1.5/85.5 ± 1.1 mm Hg) completed a GEST. Peak SBP was the highest SBP achieved during the GEST. Blood samples were taken for fasting glucose and insulin, nitric oxide (NO), and DNA. Endothelial nitric oxide synthase (NOS3, rs2070744) ?786 T > C genotyping was determined by PCR. NOS3 genotypes were combined using a dominant model [TT (n = 24); TC/CC (n = 24)]. Brachial artery reactivity (BAR) was determined via ultrasound before, 1 min, and 3 min post occlusion and calculated as % change. Analysis of variance (ANOVA) tested changes in the peak SBP GEST response by NOS3 genotype. Multiple variable regression analyses examined relationships among the GEST peak SBP response and measures of endothelial function.Results%BAR change at 1 min (r² = 0.093, p = 0.020), glucose (r² = 0.062, p = 0.014), NOS3 ?786 T > C (r² = 0.040, p = 0.024), NO (r² = 0.037, p = 0.064), and age (r² = 0.009, p = 0.014) explained 24.1% of the GEST peak SBP response (p = 0.043). The GEST peak SBP change from baseline was 11.1 ± 5.0 mm Hg higher among those with the NOS3 C allele (92.4 mm Hg + 3.8) than the NOS3 TT genotype (81.3 mm Hg + 3.2) (p = 0.03).ConclusionIndicators of endothelial function appear to explain a clinically significant portion of the GEST peak SBP response. Further investigation is needed to unravel the mechanisms by which endothelial function influences the GEST peak SBP response.     

Esophageal motor function in Familial Mediterranean Fever: A prospective evaluation of motility in 31 patients

BackgroundThe aims of this study were to evaluate esophageal motor function in patients with Familial Mediterranean Fever (FMF) who had upper gastrointestinal symptoms and to compare esophageal motor function between FMF patients who developed amyloidosis and patients without amyloidosis.Methods31 FMF patients with dyspeptic symptoms and 31 healthy age-matched individuals were included in the study. Endoscopic examination and esophageal motility testing were performed.ResultsEsophageal motor abnormalities were detected in 25.8% (8/31) of these patients [incomplete Lower esophageal sphincter (LES) relaxation: n = 4, esophageal hypomotility: n = 2, and hypotensive LES: n = 2]. Median LES relaxation (%) (min–max) was significantly lower in patients with FMF compared to control group 94% (54–100) vs. 98% (80–100), p = 0.019 respectively). However, mean LES pressure (mmHg) (19.5 ± 8.9 vs. 19.7 ± 5.6, p = 0.813), duration of LES relaxation (s) (7.9 ± 1.7 vs. 8.7 ± 1.7, p = 0.068), contraction amplitude of esophageal body (mmHg) (60.4 ± 23.3 vs. 58.2 ± 19.7, p = 0.691) and median (min–max) peak velocity (s) [3.1(? 1.43–50.3) vs. 3.1 (0.9–8.7), p = 0.435] were similar in patients with FMF compared to control group. There were no significant differences with regard to LES pressure, LES relaxation, LES relaxation duration, contraction amplitude (mmHg) and peak velocity (sc) among patients with FMF and amyloidosis, amyloidosis negative FMF patients and healthy controls.ConclusionsAbnormal esophageal manometric findings can be observed at least in a subgroup of patients with FMF regardless of amyloid status. Investigation of esophageal motor function in patients with FMF who exhibit unexplained upper gastrointestinal symptoms between attacks may be a helpful tool in order to delineate esophageal motor dysfunction.     

Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus

ObjectiveThe effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile.Research design and methodsMulticenter, randomized, open-label 6-week study investigating the effect of ezetimibe 10 mg (E), simvastatin 20 mg (S) and the combination of ezetimibe-/simvastatin 10/20 mg (C) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes (NCT01384058).ResultsFifty-six patients were screened for sdLDL, 41 were randomized, and 40 patients (12 E, 14 S and 14 C) completed the study. Total and LDL cholesterol fell by 14% (p = 0.004) and 15% (p = 0.006) with E, 22% (p < 0.001) and 32% (p < 0.001) with S, and 32% (p < 0.001) and 44% (p < 0.001) with C, respectively. E reduced the concentration of sdLDL by 20% (p = 0.043) whereas S and C reduced sdLDL by 24% (p = 0.020) and 33% (p = 0.003), respectively, and non-sdLDL by 28% (p = 0.004) and 42% (p < 0.001), respectively. However, the further drop in sdLDL by adding E to S was not significant.ConclusionEzetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes.     

Cognitive performance is impaired in coeliac patients on gluten free diet: a case-control study in patients older than 65 years of age

IntroductionRetrospective studies and case reports suggest an association between coeliac disease and impaired cognitive function.AimTo evaluate functional and cognitive performances in coeliac disease vs. control patients older than 65 years.MethodEighteen coeliac disease patients (75 ± 4 years, group A) on gluten free diet since 5.5 ± 3 years and 18 age-sex matched controls (76 ± 4 years, group B) were studied using a battery of neuropsychological tests. Results of functional and cognitive tests are expressed as “row scores” and as “equivalent scores” by relating “raw scores” to reference rank categories.ResultsBarthel Index of functional performance was similar in the 2 groups. “Raw score” was significantly lower in coeliac disease than controls for Mini Mental Test Examination (p = 0.02), Trail Making Test (p = 0.001), Semantic Fluency (p = 0.03), Digit Symbol Test (p = 0.007), Ideo-motor apraxia (p < 0.001) and Bucco-facial apraxia (p < 0.002). “Equivalent score” was also lower in coeliac disease than controls for Semantic memory (p < 0.01) and for Ideo-motor apraxia (p = 0.007).ConclusionCognitive performance is worse in elderly coeliac disease than control patients, despite prolonged gluten avoidance in coeliacs. Awareness on the increasing phenomenon of late-onset coeliac disease is important to minimize diagnostic delay and prolonged exposure to gluten that may adversely and irreversibly affect cognitive function.     

Protein and glutamine kinetics during counter-regulatory failure in type 1 diabetes

Background and aimsHealthy individuals counteract insulin-induced hypoglycaemia by increasing glutamine utilization but not proteolysis. Glucagon is important to this response because it increases glutamine uptake. In type 1 diabetes (T1DM) glucagon and epinephrine responses to hypoglycaemia are defective. We investigated whether glutamine and amino acid utilization during hypoglycaemia is altered in T1DM with defective counter-regulatory responses.Methods and resultsEight T1DM patients (duration of diabetes 14 ± 4 years and therefore with presumed defective counter-regulatory response) and eight controls (CON) received a 3 h hypoglycaemic hyperinsulinaemic (0.65 mU/kg per min) clamp coupled to [6,6-²H₂]glucose, [1-¹³C]leucine and [2-¹⁵N]glutamine to trace the relative kinetics.Post-absorptive plasma glucose and glucose uptake were increased in T1DM (9.09 ± 0.99 vs 5.01 ± 0.22 mmol/l and 19.5 ± 0.9 vs 12.6 ± 0.8 μmol/kg per min, p < 0.01). During the clamp T1DM but not CON required exogenous glucose (4.4 ± 1.7 μmol/kg per min) to maintain the hypoglycaemic plateau because the endogenous glucose production was significantly suppressed (p < 0.01). In T1DM the leucine and phenylalanine concentrations were less suppressed from basal (p < 0.05) despite a similar insulin suppression of proteolysis (−16 ± 2 vs −20 ± 4%, p = ns) indicating a defective stimulation of leucine metabolic clearance from basal (+18 ± 3% vs +55 ± 9%, p < 0.01). Glutamine concentration remained unchanged from basal (−7 ± 3% vs −35 ± 3%, p < 0.01) and the clearance of glutamine was markedly defective in T1DM (+6 ± 2%) in comparison with controls (+22 ± 4%; p = 0.02).ConclusionsIn T1DM, the counter-regulatory failure to hypoglycaemia seems to be associated with a defective glutamine utilization. The failure to clear circulating amino acids, specifically glutamine, during hypoglycaemia may adversely affect gluconeogenesis.