Computerized dynamic pupillometry indices mirrors the heart rate variability parameters.

OBJECTIVE: Dynamic pupillometry (DP) is a simple, non-invasive computerized assessment of pupillary light response which provides data concerning both branches of the autonomous nervous system (ANS). Heart rate variability (HRV) analysis assess cardiac health and the ANS modulation on the heart. In this study, we aimed to evaluate the utility of DP as a predictor of cardiac autonomic activity assessed by HRV. PATIENTS AND METHODS: A total of 44 consecutive healthy subjects (mean age = 35.9 ± 7.4 years, 24 males) were enrolled. Pupil diameters (R0, R1, R2 and R%): latency (Lc), amplitude (Ac), velocity (Vc) and duration of pupil contraction (Tc): latency (Ld), velocity (Vd) and duration of pupil dilatation (Td) were measured in DP. Time and frequency domain indices of HRV were obtained from 24-h ambulatory electrocardiographic monitoring. RESULTS: There were strong significant correlations of Vc with LF/HF (r = -0.672, p = 0.001) and a measure of HRV: RMSDD (r = 0.654, p = 0.001). R% significantly correlated with PNN50 (r = -0.432, p = 0.003) and RMSDD (r = -0.422, p = 0.004) and LF/HF (r = 0.340, p = 0.024). Vc (ß = 0.647, p = 0.011) and Ac (ß = 0.320, p = 0.013) were found as independent predictors of RMSSD. Vc (ß = 0.578, p = 0.036) was found to be only significant predictor of PNN50. Vc (ß = -0.617, p = 0.008) and R% (ß = 0.309, p = 0.038) were found to be significant predictors of LF/HF. CONCLUSIONS: Pupillary autonomic functions assessed by DP correlates with cardiac autonomic functions evaluated by HRV. Among the DP parameters analyzed, Vc was a predictor of parasympathetic indices, and R% was a predictor of sympathetic indicators of cardiac autonomic functions.

Assessment of cardiac arrhythmias in patients with ankylosing spondylitis by signal-averaged P wave duration and P wave dispersion.

OBJECTIVE: Aortic regurgitation, conduction disturbances, increased myocardial fibrosis and pericarditis could be seen in ankylosing spondylitis (AS). However, less attention has been paid to supraventricular arrhythmias (SVA) and atrial conduction system changes. We aimed to assess SVA and conduction system changes in patients with AS. PATIENTS AND METHODS: Twenty-eight patients (24 men; mean age, 28.7 ± 5.7 years) with AS and 30 healthy volunteers (26 men; mean age, 29.3 ± 5.8 years) were enrolled. All subjects were evaluated by 24-hour ambulatory electrocardiogram, 12 lead standard electrocardiogram (ECG) for P wave dispersion (Pd), and signal-averaged ECG (SAECG) for P wave duration (SAPWD). RESULTS: SVAs were detected in 9 patients with AS (32%) and 3 controls (10%; p =0.02). Mean SAPWD (115.7±28.6 ms vs. 100.2 ± 18.7 ms, p =0.017) and mean Pd (11.9±4.8 ms vs. 9.3±3.6 ms, 0.023) was longer in patients with AS than the control group. When patient with AS were divided into 2 subgroups as patients with or without SVA, the Pd (16.2±5.0 vs. 9.9±3.2, p =0.001), SAPWD (151.4±7.8 vs. 98.7±16.1, p =0.001) and Bath ankylosing spondylitis disease activity index (BASDAI) (5.1±1.6 vs. 3.7±1.0, p =0.014) were significantly greater in the subgroup with arrhythmias compared to the subgroup without arrhythmias. There was a moderate positive correlation between BASDAI and SAPWD (r=0.622, p =0.001). There was also a moderate positive correlation between BASDAI and Pd (r=0.479, p =0.01). CONCLUSIONS: SVA were detected more frequently in AS than control group. SAPWD and Pd were prolonged in patients with AS. Clinical severity assessed with BASDAI had a positive correlation with prolongation of SAPWD and Pd.

Assessment of the relationship between dynamic pupillometry and exercise heart rate recovery among healthy subjects.

OBJECTIVE: Dynamic pupillometry (DP) is a simple, non-invasive computerized technique for assessment of pupillary light response which provides data concerning the balance of both branches of the autonomous nervous system (ANS). Heart rate (HR) recovery (HRR) after graded exercise reflects cardiac autonomic activity and predicts cardiovascular events. In this study, we aimed to evaluate the utility of DP as a predictor of cardiac autonomic activity assessed by HRR. PATIENTS AND METHODS: A total of 62 consecutive healthy subjects (mean age = 33.7 ± 8.6 years, 39 males and 23 females) were enrolled. Pupil diameters (R0, R1, R2 and R%): latency (Lc), amplitude (Ac), velocity (Vc) and duration of pupil contraction (Tc): latency (Ld), velocity (Vd) and duration of pupil dilatation (Td) were measured in DP. HRR indices were calculated by subtracting 1st (HRR1), 2nd (HRR2) and 3rd (HRR3) minute HR from the maximal HR during treadmill exercise stress test. RESULTS: HRR1 was 32.9 ± 8.0 bpm, HRR2 was 55.1 ± 11.6 bpm and HRR3 was 58.3 ± 12.7 bpm, respectively. Correlation analysis revealed significant positive correlations of HRR1 with Vc (r = 0.660, p = 0.001), Ac (r = 0.559, p = 0.001) and Vd (r = 0.412, p = 0.001). HRR had significant negative correlations with Lc (r = -0.442, p = 0.001), R% (r = -0.384, p = 0.002) and Ld (r = -0.286, p = 0.025). Vc [ß = 3.995 (1.040 to 6.951, 95% CI, p = 0.009)] and Lc [ß = -0.032 (-0.056 to -0.008, 95% CI, p = 0.01)] were found to be significant independent predictors of HRR1. CONCLUSIONS: Pupillary autonomic functions assessed by DP correlates with cardiac autonomic functions evaluated by HRR. Among the DP parameters analyzed, Vc and Lc were independent predictors of cardiac autonomic functions.

High-grade proteinuria as a cardiovascular risk factor in renal transplant recipients.

BACKGROUND: Proteinuria is a marker of graft damage and is closely associated with a higher risk of morbidity, mortality, and cardiovascular disease in kidney transplant recipients (KTRs). Arterial stiffness is a well-known predictor of vascular calcification and systemic arteriosclerosis. In our study, we aimed to investigate the association between proteinuria and graft/patient survival and to determine whether proteinuria may be a predictor for cardiovascular disease in our KTR population. METHODS: Ninety KTRs (31 women; age, 38.7 ± 11 years, with 45.9 ± 9.6 months post-transplantation period) with normal graft functions in the 3 to 5 years of the post-transplantation period were enrolled. All patients were evaluated for their standard clinical (age, sex, and duration of hemodialysis) parameters. High-grade proteinuria was defined as proteinuria >500 mg/day in the 24-hour urine collection. All patients were evaluated by means of pulse-wave velocity (PWV) measurement at the initiation of the study. RESULTS: Patients were divided into 2 groups: group 1 (high-grade proteinuria) patients with ≥500 mg/24 hours (n = 30) and group 2 (low-grade proteinuria) patients with <500 mg/24 hours (n = 60). High-grade proteinuria was correlated with higher PWV measurements and lower estimated glomerular filtration levels. Proteinuria appears to precede the elevation of serum creatinine and thus may be a useful marker of renal injury and may also be a contributing factor on deterioration of the graft. CONCLUSIONS: High-grade (>500 mg/day) proteinuria in KTRs is strongly associated with poor graft survival and increased risk of cardiovascular events. In our study, we proved the significant difference between high-grade and low-grade proteinuric patients, and we suggest 500 mg/day as the threshold of proteinuria in KTR population.

Reliability of bioelectrical impedance analysis in the evaluation of the nutritional status of hemodialysis patients - a comparison with Mini Nutritional Assessment.

INTRODUCTION: Protein-energy wasting (PEW) is a strong predictive factor for morbidity and mortality in patients who have end-stage renal disease (ESRD). Mini Nutritional Assessment (MNA) is an important and confirmed tool to evaluate PEW that has been recommended by many guidelines. Bioelectrical impedance analysis (BIA) is a noninvasive technique for assessing body composition. The aim of the present study was to analyze the reliability of BIA in malnutrition diagnosis by comparing it with standard MNA in a group of 100 ESRD patients. METHODS: One hundred ESRD patients who were medically stable and under dialysis treatment for at least 6 months were enrolled to the study. Monthly assessed serum creatinine, albumin, C-reactive protein (CRP), and lipid profiles from the last 6 months prior to the study were retrospectively collected. A standard Full-MNA and body composition analyses were applied to all patients. Body compositions were analyzed with the BIA technique using the Body Composition Analyzer (Tanita BC-420 MA; Tanita, Tokyo, Japan). Patients were classified into three groups according to MNA scores as PEW (n = 15, score <17), moderate PEW or risk group (n = 49, score 17-23.5), and well-nourished (n = 36, score ≥ 24) patients. RESULTS: Mean duration of maintenance hemodialysis treatment was significantly shorter in the PEW group compared to both of the other groups described (P = .015). Well-nourished and risk groups had lower CRP and higher albumin levels compared to PEW patients; however, these values were statistically similar in these two groups (P = .018, .01, respectively). According to BIA findings, well-nourished patients had the highest fat ratio, fat mass, muscle mass, visceral fat mass, and fat-free mass compared to both moderate the PEW/risk and the PEW groups (P < .05). Risk group patients also had higher muscle mass, visceral fat mass, and fat-free mass values compared to the PEW group (P < .05). A correlation analysis revealed that MNA scores were positively correlated with albumin (P = .005), creatinine (P = .049), fat mass (P = .045), muscle mass (P = .001), visceral fat ratio (P = .007), and BMI (P = .047) and in negative correlation with CRP (r = -0.357, P = .0001) levels. CONCLUSIONS: We recommend BIA as a complementary diagnostic tool to evaluate nutritional status of ESRD along with MNA, anthropometric measures, and classical biochemical markers.

Pulmonary hypertension in patients with end-stage renal disease undergoing renal transplantation.

INTRODUCTION: Pulmonary hypertension (PHT) has been reported to occur in a considerable proportion of patients with end-stage renal disease (ESRD). It is a progressive condition of the pulmonary circulation that poses prognostic importance. In this study, we sought to investigate the prevalence and the predictors of PHT among ESRD patients undergoing renal transplantation. PATIENTS AND METHODS: We retrospectively evaluated the records, clinical and demographic data as well as laboratory results of 500 adult patients who underwent renal transplantation at our institution. A comprehensive Doppler echocardiographic examination was performed in all patients as part of the preoperative assessment. Systolic pulmonary artery pressure (SPAP) was calculated using Bernoulli equation; a value of >30 mm Hg was accepted as PHT. RESULTS: The mean age of the study population was 31.6 +/- 10.2 years. The mean duration of dialysis was 40 months; 432 patients (86.4%) were on hemodialysis (HD) and 68 (13.6%) on peritoneal dialysis (PD). PHT was detected in 85 (17%) patients with a mean SPAP of 46.7 +/- 8.7 mm Hg (range = 35-75 mm Hg). The mean age, sex, and laboratory variables were similar between patients with versus without PHT (P > .05 for all). The mean duration of dialysis therapy was longer in the PHT group than those subjects with normal SPAP (50.8 vs 38.5 months; P = .008). Concerning the type of dialysis, the ratio of patients having PHT was higher in the HD compared with the PD group (18.8% vs 5.9%; P = .008). The prevalence of chronic obstructive pulmonary artery disease, asthma, smoking, hypertension, and diabetes mellitus did not differ between patients with versus without PHT (P > .05 for all). CONCLUSION: The findings of this study revealed that PHT was a common clinical condition among patients with ESRD evaluated for renal transplantation. The time on renal replacement therapy particularly HD as the treatment was associated with greater prevalences. Since it may be of prognostic importance in patients undergoing renal transplantation, a careful preoperative assessment including a comprehensive Doppler echocardiographic examination is needed to identify PHT.

Conversion to sirolimus for chronic allograft nephropathy and calcineurin inhibitor toxicity and the adverse effects of sirolimus after conversion.

BACKGROUND: Chronic allograft nephropathy and calcineurin inhibitor toxicity may cause graft loss. After kidney transplantation, especially among those patients with chronic allograft nephropathy, sirolimus may be a good alternative to calcineurin inhibitors. Unlike calcineurin inhibitors, sirolimus is devoid of significant nephrotoxicity, but approximately 30% to 50% of patients on sirolimus therapy display mild or severe adverse effects. We sought to report our experience with sirolimus conversion among patients with chronic allograft nephropathy as well as the mild versus severe adverse effects that limit the drug's use. MATERIALS AND METHODS: We analyzed the outcomes of 88 patients (64 men and 24 women) of overall mean age of 35.9 +/- 9.9 years (range, 21-59 years) who had undergone kidney transplantation. Immunosuppressive therapy had been converted from a calcineurin inhibitor to sirolimus because of biopsy-proven chronic allograft nephropathy, calcineurin inhibitor toxicity, or presence of malignancy. We excluded patients with prior acute rejection episodes. Subjects were divided into two groups with respect to their creatinine levels: Group A < 2 mg/dL and Group B >or= 2 mg/dL. After conversion to sirolimus, possible adverse effects of sirolimus were evaluated at the follow-up inset. Each patient underwent a physical examination, and estimation of serum lipid and electrolyte levels as well as hemoglobin concentration. RESULTS: At the time of conversion of the 88 renal transplant patients, their mean duration after grafting was 48 +/- 15 months (range, 4-296). The prior treatment consisted of a calcineurin inhibitor, prednisolone, and mycophenolate mofetil. After conversion, the calcineurin inhibitor was stopped and sirolimus was begun. The 48 Group 2 patients (34 men, 14 women) of overall mean posttransplant time of 22.7 +/- 14.6 months who underwent conversion displayed a mean serum creatinine increase to 3.2 +/- 1.4 mg/dL, including 17 subjects who underwent rejection. The 40 Group 1 patients (30 men, 10 women) with a mean overall posttransplant period of 67.6 +/- 49.9 months showed an fall in serum creatinine level to 1.4 +/- 0.5 mg/dL among only 3 patients. While 5/88 patients showed no increase in proteinuria (5.6%); 83 (94.4%) did experience it. Proteinuria increased from a mean of 192 +/- 316 to 449 +/- 422 mg/d. Only three patients displayed heavy proteinuria (>3 g/d); sirolimus was discontinued for this reason. Proteinuria was well controlled in the other patients with angiotensin-converting enzyme and/or angiotensin II receptor inhibitor agents. After sirolimus conversion, serum cholesterol levels increased from 187 +/- 42 to 214 +/- 52 mg/dL, and serum triglyceride levels increased from 161 +/- 61 to 194 +/- 102 mg/dL. All but four patients responded to statin therapy, with serum lipid levels falling to acceptable levels. Another four patients developed unilateral lower extremity edema with sirolimus discontinued for this reason. One patient displayed generalized arthralgia. CONCLUSION: Chronic allograft nephropathy or calcineurin inhibitor toxicity can lead to loss of graft kidney function. Calcineurin inhibitor toxicity can lead to chronic allograft nephropathy. Patients with a low baseline serum creatinine level who undergo sirolimus conversion showed stabilized kidney function. Late conversion of patients with a serum creatinine above 2 mg/dL face a risk of graft failure. Sirolimus displayed a limited incidence of serious adverse effects; mild or moderate adverse effects, such as hyperlipidemia and proteinuria, were easily controlled with countermeasure therapy.

Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery.

Mucosal application of a vaccine can effectively induce both systemic and mucosal immune responses. In general, mucosal applications of antigens result in poor immune responses. Therefore, adjuvant/delivery systems are required to enhance the immune response. Chitosan is a cationic biopolymer which exerts advantages as a vaccine carrier due to its immune stimulating activity and bioadhesive properties that enhance cellular uptake and permeation as well as antigen protection. Similar effects are also shown by chitosan derivatives. In this study, the nanoparticulate systems were prepared by using differently charged chitosan derivatives, N-trimethyl chitosan (TMC, polycationic), and mono-N-carboxymethyl chitosan (MCC, polyampholytic) for mucosal immunisation. The derivatives were synthesised and characterised in-house. The aqueous dispersions of the derivatives were also prepared for comparison. The cytotoxicity studies (MTT assay) on Chinese hamster ovary (CHO-K1) cell lines showed that cell viability was in the order of MCC, chitosan and TMC. Nanoparticles were prepared using ionic gelation method and loaded with tetanus toxoid (TT). Nanoparticles with high loading efficacy (>90% m/m), particle size within the range of 40-400nm, with a negative surface charge for MCC and positive surface charge for TMC and chitosan were obtained. The structural integrity of the TT in the formulations was confirmed by SDS-PAGE electrophoresis analysis. The effective uptake of the FITC-BSA loaded nanoparticles into the cells was demonstrated by cellular uptake studies using J774A.1 cells. Immune responses induced by the formulations loaded with tetanus toxoid were studied in vivo in Balb/c mice. Enhanced immune responses were obtained with intranasal (i.n.) application of nanoparticle formulations. Chitosan and TMC nanoparticles which have positively charged surfaces induced higher serum IgG titres when compared to those prepared with MCC which are negatively charged and smaller in size. Nanoparticle formulations developed in this study can be used as promising adjuvant/delivery systems for mucosal immunisation.

Comparison of tissue Doppler echocardiography parameters in patients with end-stage renal disease and renal transplant recipients.

BACKGROUND: Tissue Doppler echocardiography has been introduced as a useful tool to assess systolic myocardial function. In this study we sought to compare patients with end-stage renal disease (ESRD), with renal transplantations and control subjects with regard to tissue Doppler parameters. METHODS: Thirty recipients with functional grafts of overall mean age 36 +/- 7 years included 24 men. An equal number of patients with ESRD of overall mean age 35 +/- 7 years included 20 men. A third cohort was comprised of 20 age- and gender matched control subjects. Tissue Doppler imaging from the septal and lateral mitral annulus of the left ventricle and free wall of the right ventricle was performed from a 4-chamber view. RESULTS: Mean systolic and diastolic blood pressures were similar among the groups during imaging. Peak systolic velocity (S wave) at the septal annulus was similar in control subjects and recipients. S waves were significantly lower among ESRD patients compared with recipients (10.3 +/- 2.1 vs 12.0 +/- 2.5 cm/s, P = .04, respectively). Isovolumic contraction velocity of the septum and the right ventricular wall were significantly lower in ESRD patients than recipients or controls: 10.2 +/- 2.6 vs 12.5 +/- 2.8 vs 11.4 +/- 1.8 cm/s for septal wall (P = .008) and 13.9 +/- 3.6 vs 17.9 +/- 5.1 vs 16.8 +/- 5.8, for right ventricle (P = .01). CONCLUSION: Systolic indices of tissue Doppler echocardiography in recipients demonstrated similar values as control subjects and increased values compared with ESRD patients. These results suggested improvement in systolic myocardial function following renal transplantation.

Ultrasonography and fluoroscopy-guided insertion of chest ports.

AIMS: To evaluate the results of ultrasonography and fluoroscopy-guided percutaneous placement of internal jugular vein catheters and subcutaneous chest port system in patients with carcinoma. METHODS: The data of 1418 patients in whom the devices were implanted from 2003 to 2007 in interventional radiology unit were evaluated prospectively. RESULTS: The median age was 45 years (range 23-70), 658 were women and 760 were men. Technical success in implanting the devices was 100%. No instances of major complications such as pneumothorax, hemothorax, catheter tip malposition, air embolism were seen. The overall complication rate was 5%. Overall follow-up of patients was 699 074 catheter days with the mean function time of 493 (range 130-1215) days. CONCLUSIONS: With the benefit of ultrasonography and fluoroscopy guidance, chest port systems can be implanted by interventional radiologists without major insertion complications and with a higher success rate than those reported in surgical placements.

Risk factors for osteoporosis in young renal transplant recipients.

Osteoporosis is a frequent complication after renal transplantation. Although several risk factors have been defined in its pathogenesis, the parameters influencing this complication in young patients with functioning grafts have not been well defined. We sought to determine the possible risk factors for osteoporosis among 55 male and 27 female renal transplant patients of mean age 35.5 +/- 11.7 years with 68.8% recipients of living-related grafts. Bone mineral densitometry was performed in all patients at 1 year after transplantation. The study utilized the World Health Organization recommendations that define normal (group 1, n = 19), osteopenic (group 2, n = 24), or osteoporotic (group 3, n = 39) patients according to T-score values. Pre- and posttransplant data included gender, age at dialysis onset; age at transplantation; pretransplant dialysis duration; body mass index (BMI); serum calcium, albumin, phosphorus, parathyroid hormone (PTH), and C-reactive protein levels; lipid profile, cumulative doses of immunosuppressive drugs, and pulse steroid dose. Differences between groups 1 and 3 showed that patients with osteoporosis were younger (P < .003) and had started dialysis and underwent transplantation at a younger age than those without osteoporosis (P < .01, P < .003). In addition, pretransplant body weight (P < .02), posttransplant BMI (P < .01), and pretransplant PTH (P < .04), posttransplant total cholesterol, and high-density lipoprotein cholesterol levels were lower among group 3 (P < .004, P < .003). Young adults who started dialysis and underwent transplantation at a younger age were prone to osteoporosis. Additionally, high BMI and cholesterol levels seemed to be preventative for bone loss after transplantation.