Evolution of coronary artery calcification in patients with chronic kidney disease Stages 3 and 4, with and without diabetes.

BACKGROUND: The purpose of this study was to report the evolution of coronary artery calcification (CAC) in subjects with chronic kidney disease Stages 3 and 4 comparing those with and without diabetes. We previously reported prevalence in the same population. METHODS: CAC was measured using multi-slice computer tomography. We prospectively followed up 103 patients for 2 years, 49 with diabetes and 54 without diabetes. Demographic, routine biochemistry, calcification inhibitors and bone mineral density data were collected and analysed. Evolution of CAC was defined as those with a difference of ≥ 2.5 U between baseline and final square root CAC scores. RESULTS: There were more progressors in the group with diabetes, 24 compared to 12 in the group without diabetes (P= 0.004). When diabetes was present, CAC progressed equally in men and women. Risk factors for evolution of CAC included age, baseline CAC score and serum phosphate levels. Baseline CAC score, phosphate and body mass index were independent predictors for the increase of CAC score during the study period. Severity of CAC was greater in the diabetes group (median CAC score at baseline in the group with diabetes 154 increased to 258 2 years later, P < 0.001). CONCLUSIONS: Evolution of CAC is greater in older patients and those with diabetes, where the gender advantage of being female is lost. Serum phosphate level, despite being within the normal range and virtually no use of phosphate binders, was also a risk factor. Further studies are required to determine the levels of serum phosphate required to minimize cardiovascular risk.

Relationship between vitamin D status, parathyroid hormone levels and bone mineral density in patients with chronic kidney disease stages 3 and 4.

AIM: Low vitamin D status is associated with secondary hyperparathyroidism and increased bone turnover in the general population and can aggravate the hyperparathyroidism of chronic kidney disease (CKD) patients. It is also correlated to low bone mineral density (BMD), but this correlation is less clear in CKD patients. Aims of our study were to investigate these associations in CKD stages 3 and 4 patients, and to identify significant predictors of BMD in this population. METHODS: Serum 25-hydroxyvitamin D (25OHD) levels, BMD at the femur and radius, and bone mineral metabolism parameters were measured in 89 CKD stages 3 and 4 patients. Vitamin D status was defined according to the NKF/KDOQI guidelines. RESULTS: Mean 25OHD levels were 53.8+/-32.1 nmol/L and correlated to the severity of proteinuria. Thirty-five patients (39%) had vitamin D insufficiency, 29 (33%) had vitamin D deficiency and five (6%) had severe deficiency. Of the 89 patients, two had osteoporosis and 31 had osteopenia either at femur or radius. Independent predictors for the total femur BMD were the intact parathyroid hormone (iPTH) levels and the body mass index (BMI). For the total radius BMD, independent predictor was only the BMI. Serum 25OHD levels were not directly associated with BMD, but they were independent predictors of iPTH. CONCLUSION: Vitamin D insufficiency and deficiency are very common in CKD stages 3 and 4 population and may indirectly affect, via effects on iPTH, the BMD of these patients.

The effect of a single haemodialysis session on functional mobility in older adults: a pilot study.

OBJECTIVES: To undertake balance and functional mobility assessments in older maintenance haemodialysis patients before and after haemodialysis as a pilot study in order to gain initial data and to assess the feasibility and acceptability of this type of study. DESIGN: Postural sway, three-metre timed "up and go" test (TGUGT), and dynamic single leg extensor power (LEP) were measured before and after a haemodialysis session. SETTING AND SUBJECTS: Male and female maintenance haemodialysis patients aged over 60 years attending the Nottingham City Hospital. MAIN MEASURES: Objective outcome measures were postural sway number and sway path (mm) by balance performance monitor, timed three-metre "up and go" test (s), and leg extensor power (W). Blood pressure and weight reductions were also measured. Subjective assessments of practicality and acceptability were made. RESULTS: Twenty-two patients enrolled. Complete data sets were collected for 14 subjects (11 male, three female). Results were analysed using the Wilcoxon signed ranks test for nonparametric data. There was no significant difference before and after dialysis in postural sway, timed "up and go" or leg extensor power. Eight patients did not complete the study and the reasons are examined. CONCLUSIONS: There was no significant single-session effect. Results suggest that haemodialysis patients may be weaker and have reduced postural stability when compared to historical data on comparable undialysed patients. The study was logistically complex and would be difficult to expand using these methods, but the issues merit further consideration.

Detection of coronary and peripheral artery calcification in patients with chronic kidney disease stages 3 and 4, with and without diabetes.

BACKGROUND: The purpose of this study was to describe the prevalence and extent of coronary artery calcification (CAC) in subjects with chronic kidney disease (CKD) stages 3 and 4 comparing those with and without diabetes. We also wished to determine if the presence of peripheral artery calcification (PAC) would assist in identifying patients positive for CAC. METHODS: CAC was detected by multi-slice computed tomography and PAC was detected by plain foot radiography. Study population was 112 patients, 54 with diabetes and 58 without, all asymptomatic for heart disease. Demographic and laboratory data were collected and analysed. RESULTS: The prevalence of CAC in CKD patients was 76 and 46.5% with and without diabetes, respectively. Patients with diabetes had higher CAC scores with more vessels affected, and in the presence of diabetes men and women had the same risk for CAC. In patients with diabetes, age was the unique explanatory variable for detecting the presence of CAC, while age and smoking history predicted severity. In patients without diabetes, age, male gender, body mass index, estimated glomerular filtration rate and serum phosphate levels predicted the presence of CAC, while parathyroid hormone predicted severity. Prevalence of PAC was 63 and 12% in subjects with and without diabetes. PAC detected by foot radiography was not an adequate alternative-screening marker for identifying patients with CAC. CONCLUSIONS: CAC is common in CKD stages 3 and 4 patients, especially in men and women with diabetes.

Reduced bone mineral density in male renal transplant recipients: evidence for persisting hyperparathyroidism.

BACKGROUND: Osteoporosis is increasingly recognized as a major source of morbidity following renal transplantation. The aim of this cross-sectional study was to determine the prevalence of osteoporosis in a cohort of male transplant recipients and examine factors that may influence their bone loss. METHODS: Bone mineral density (BMD) and biochemical markers of bone metabolism were measured in 134 out of 154 male renal allograft recipients in our center. RESULTS: The mean age of the patients was 49.7 years (range 26-76) with a median of 6 years post-transplant. Only 17% had normal BMD, 30% were osteoporotic at either hip or spine, and this proportion rose to 41% if the ultradistal radius was included. Parathyroid hormone (PTH) was negatively correlated with BMD at all skeletal sites. In a multiple regression model, independent predictors of femoral neck BMD included body mass index (p=0.004), diabetes (p=0.025), and PTH (p=0.049). The only independent predictor of BMD at the ultradistal radius was PTH (p<0.001). Nineteen men sustained a total of 25 appendicular fractures after transplantation (median time to fracture was 3 years). Prevalent vertebral fractures were only identified in five men. PTH was elevated in 72.4% of patients (mean PTH 142 +/- 118 pg/ml). Bone resorption markers were increased in 48% of patients. PTH was positively correlated with serum carboxyterminal telopeptide of type 1 collagen (r=0.473, p<0.001) and procollagen type 1 amino terminal propeptide (r=0.419, p<0.001). CONCLUSIONS: Osteopenia and osteoporosis are common in male transplant recipients, and the hip and radius are the most severely affected sites. Elevated rates of bone resorption driven by hyperparathyroidism appear to be the most important contributing factor.

Functional significance of the ipsilateral hemisphere during movement of the affected hand after stroke.

Previous fMRI observations have suggested increased task-related activation of the ipsilateral cerebral motor cortex in patients recovering from stroke. This is generally taken to infer an increased output from this area, although the functional relevance of this has been questioned. Here, we use directed EEG coherence to reveal whether there is increased informational flow from the ipsilateral motor cortex following motor stroke, and through correlation with degree of recovery, establish that this pattern of activity is associated with limited functional improvement. Unrecovered (n = 14), recovered (n = 11) patients and healthy subjects (n = 16) performed an isometric grip task with either hand that corresponded to 25% of individual maximum force, while EEG was recorded. For unrecovered stroke patients, most task-related information flow between the sensorimotor cortices in the low beta band of the EEG came from the ipsilateral (undamaged) hemisphere during grip with the affected hand. This was not the case when they gripped with their unaffected hand, when cortical activity was driven from the contralateral sensorimotor cortex. The latter pattern was also seen in recovered patients and controls. These findings suggest a functional role for the ipsilateral hemisphere in organizing movement of the impaired limb following stroke, but only in those patients that do not make a good functional recovery. Patients making a fuller recovery organize movement-related cortical activity from the hemisphere contralateral to movement.

Anticipatory cortico-cortical interactions: switching the task configuration between effectors.

Cognitive regulation enables a subject to plan actions according to context and to respond in a flexible manner to environmental conditions. This implies that foreknowledge about a change in system configuration will trigger preparatory activity in anticipation of the impending transformation. In the present study, we evaluate a unimanual task under two performance conditions that affected the cognitive context, and examine modulations in cortico-cortical interactions as determined by EEG coherence. The right hand movement was performed in an experimental paradigm that necessitated in some trials a voluntary and predictable switch towards a left hand movement, whereas in other trials no switch was required and movement of the right hand continued. The data showed that execution of the right hand movement was associated with an increased degree of task-related coherence in the alpha frequency band (8-12 Hz) in the switching as compared to the no switching condition, and this was most apparent for fronto-parietal connections of the movement-driving (left) as well as for the primed (right) hemisphere. For the primed hemisphere, we observed that the information flow was driven from the F4 electrode overlying the prefrontal area, which suggests that anticipatory preplanning occurred. These data indicate that higher-order cognitive operations bias cortico-cortical interactions in respect of an upcoming switch of the task settings between effectors by recruiting neural resources proactively. Dynamic adjustments in the alpha band suggest that low frequency activity is a characteristic of distributed information processing related to movement planning.

The importance of the dominant hemisphere in the organization of bimanual movements.

The successful control of upper limb movements is an essential skill of the human motor system. Yet, the neural organization of bimanual actions remains an issue of debate. Their control can be directed from both hemispheres, or, coordinated motion might be organized from the dominant (left) hemisphere. In order to unravel the neural mechanisms of bimanual behavior, we analyzed the standard task-related and directed coherence between EEG signals picked up over the primary sensorimotor cortices in right-handed subjects during unimanual as well as bimanual in-phase (symmetrical) and anti-phase (asymmetrical) movements. The interhemispheric coherence in the beta frequency band (>13-30 Hz) was increased in both unimanual and bimanual patterns, compared to rest. During unimanual actions, the drive in the beta band from one primary sensorimotor cortex to the other was greater during movement of the contralateral as opposed to ipsilateral hand. In contrast, during bimanual actions, the drive from the dominant to the non-dominant primary sensorimotor cortex prevailed, unless task constraints induced by an external perturbation resulted in a substantial uncoupling of the hand movements, when interhemispheric coherence would also drop. Together, these results suggest that the contralateral hemisphere predominantly organizes unimanual movements, whereas coupled bimanual movements are mainly controlled from the dominant hemisphere. The close association between changes in interhemispheric coupling and behavioral performance indicates that synchronization of neural activity in the beta band is exploited for the control of goal-directed movement.

Total hip bone mass predicts survival in chronic hemodialysis patients.

BACKGROUND: Bone mass measurements are widely used to diagnose osteoporosis and identify patients at risk for fractures. Recent studies have shown that reduced bone mass is also predictive of all-cause and cardiovascular mortality in healthy postmenopausal women. Among chronic hemodialysis patients reduced bone mass resulting from the combined effects of age-related factors and renal osteodystrophy has been associated with vascular calcification. In this prospective study, we investigated the ability of bone mass measurements to predict mortality in chronic hemodialysis patients. METHODS: Eighty eight patients underwent hip bone mass measurements by dual energy x-ray absorptiometry (DEXA) and were followed up for a mean of 3.5 years. Eleven patients received renal transplants and were therefore excluded. Forty of the remaining patients died, predominantly due to cardiovascular causes (43%). RESULT: Cox regression analysis showed patient age, osteoporosis or osteopenia, and baseline average calcium x phosphate product (Ca x P) to be independently predictive of increased mortality. Patients with osteopenia or osteoporosis had a 3.3- and 4.3-fold increased risk of death, respectively. A Ca x P of >or=5.0 mmol2/L2 predicted a threefold increased risk of death. Previous renal transplantation predicted a lower mortality. CONCLUSIONS: This study has shown for the first time that reduced total hip bone mass is an independent predictor of all-cause mortality among chronic hemodialysis patients. Our findings suggest that reduced bone mass and elevated Ca x P may be involved in the pathogenesis of cardiovascular disease in these patients but further research is required to investigate the possible mechanisms for these associations.

Bayesian nonstationary autoregressive models for biomedical signal analysis.

We describe a variational Bayesian algorithm for the estimation of a multivariate autoregressive model with time-varying coefficients that adapt according to a linear dynamical system. The algorithm allows for time and frequency domain characterization of nonstationary multivariate signals and is especially suited to the analysis of event-related data. Results are presented on synthetic data and real electroencephalogram data recorded in event-related desynchronization and photic synchronization scenarios.

Treatment of chest pain in patients with noncardiac, nonreflux, nonachalasia spastic esophageal motor disorders using botulinum toxin injection into the gastroesophageal junction.

OBJECTIVE: The aim of this study was to determine if botulinum toxin injection in the gastroesophageal junction improves symptoms in patients with noncardiac chest pain with a spastic esophageal motility disorder. METHODS: Twenty-nine noncardiac chest pain patients with nonachalasia, nonreflux-related spastic esophageal motility disorders were enrolled in this open label trial of botulinum toxin injection at the gastroesophageal junction. Chest pain was the major complaint in all patients. Symptoms of chest pain, dysphagia, regurgitation, and heartburn were scored before and 1 month after botulinum toxin injection. A response to botulinum toxin was defined as at least a 50% reduction in the symptom score with a possible total chest pain score of 4. The duration of response was defined as the time period, between the time of injection and the point in time, at which the severity of the symptoms returned to the preinjection score. RESULTS: Seventy-two percent of the patients responded with at least 50% reduction in chest pain. In these responders, there was a 79% reduction in the mean chest pain score from a preinjection score of 3.7 to a postinjection score of 0.78 (p < 0.0001). The mean duration of the response for chest pain in these patients was 7.3+/-4.1 months (range 1-18 months). There was also a significant reduction in the mean regurgitation score, dysphagia score, and total symptom score (p < 0.0001). CONCLUSIONS: Botulinum toxin injection at the gastroesophageal junction leads to significant symptomatic improvement in patients with spastic esophageal motility disorders whose major complaint is chest pain.

Comparison of intact and 'whole molecule' parathyroid hormone assays in patients with histologically confirmed post-renal transplant osteodystrophy.

BACKGROUND: Fragments of parathyroid hormone (PTH) have been identified (amino acids 7-84) which may interfere with commercially available 'intact molecule' PTH assays. Novel assays which employ an antibody directed to the first seven amino acids of the N-terminus of PTH are thought to be free from cross-reactivity with the 7-84 fragments, and therefore measure true 'whole molecule' PTH. Transplant recipients (as well as those in end-stage renal failure) have been reported to have elevated levels of 'intact' in comparison with 'whole molecule' PTH. METHODS: PTH concentrations were assessed in serum samples obtained from female renal transplant recipients previously classified as either having hyperparathyroid (n = 14) or adynamic bone disease (n = 14) by transiliac crest bone biopsy. PTH was measured as 'whole molecule' (Scantibodies 'whole molecule' PTH) and 'intact' (DPC Immulite 2000 intact PTH and Scantibodies total PTH). RESULTS: Scantibodies 'whole molecule' PTH (all-subject mean 48.7 ng/L, +/- 53.0) were significantly lower than DPC intact (83.5 ng/L, +/- 88.1; P < or = 0.0001) and Scantibodies total PTH (80.5 ng/L, +/- 92.4; P < or = 0.0001). However, the differences between the 'whole molecule' and 'intact' measurements were similar across the two patient groups, and reflected the lower reference range employed by the 'whole molecule' assay. CONCLUSION: The 'whole molecule' PTH assay was unable to discriminate between the two patient populations and provided very little additional clinical information to that obtained from the intact PTH assays.