Systematic use of a collagen-based vascular closure device immediately after cardiac catheterization procedures in 1,317 consecutive patients.

Despite recent advances in interventional cardiology, vascular access complications continue to be a significant problem. Conventional manual compression of the femoral access site is associated with prolonged immobilization and significant patient discomfort. We investigated the performance of a collagen-based closure device applied immediately after catheterization and its complication rate in 1,317 consecutive patients undergoing cardiac catheterization or coronary angioplasty. Patients undergoing coronary angioplasty (n = 644) received more heparin than patients with diagnostic cardiac catheterization (n = 673; 9,675 +/- 1,144 IU vs. 6,419 +/- 2,211 IU; P < 0.0001). Deployment success rates of the closure device were comparable for patients undergoing diagnostic vs. interventional procedures (95.8% vs. 96.7%; P = 0.46). Complete hemostasis immediately after deployment of the device was achieved in > 90% of all patients, but was lower in the interventional group (93.7% vs. 90.6%; P = 0.05). Major complications including any vascular surgery, major bleeding requiring transfusion, retroperitoneal hematoma, thrombosis or loss of distal pulses, groin infections, significant groin hematoma, and death were observed in 0.53% of all patients, with no differences between diagnostic or interventional patients (0.62% vs. 0.45%; P = 0.953). Subgroup analysis revealed female gender as a predictor of access site complications. Systematic sealing of femoral access sites after both diagnostic and interventional procedures allows for immediate sheath removal with reliable hemostasis. The use of a collagen-based closure device is associated with a low rate of clinically significant complications.     

Frequency of osteopenia in adolescents with early‐onset juvenile idiopathic arthritis: A long‐term outcome study of one hundred five patients

Objective

To determine the frequency of low bone mineral content (BMC) and low bone mineral density (BMD) as long‐term complications in adolescents with early‐onset juvenile idiopathic arthritis (JIA), and to identify disease variables, patient characteristics, and biochemical bone markers related to low bone mass.

Methods

One hundred five (87%) of 121 adolescent patients with early‐onset JIA (ages 13–19 years, 80 girls and 25 boys, mean age at onset of JIA 2.8 years), from a cohort first admitted to the hospital between 1980 and 1985, were assessed after a mean disease duration of 14.2 years. BMC and BMD of the total body, the lumbar spine at L2–L4, and the femoral neck were measured by dual‐energy x‐ray absorptiometry. Age‐ and sex‐specific reference values from a pooled, healthy reference population were used to calculate Z scores. Low bone mass was defined as a Z score less than −1 SD.

Results

Among the 103 adolescent JIA patients who underwent total‐body imaging, 41% had low total‐body BMC and 34% had low total‐body BMD. Compared with adolescent JIA patients who had normal total‐body BMC, those with low BMC had lower mean weight (P < 0.001), height (P < 0.001), lean mass (P < 0.001), and remission rates (P = 0.016), had longer duration of active disease (P = 0.013), had higher numbers of active and mobility‐restricted joints (P < 0.001 and P = 0.001, respectively), had more disability (P = 0.011), had higher frequencies of joint erosions (P < 0.001), and had higher erythrocyte sedimentation rates (P = 0.033). In multiple linear regression analyses of total‐body BMC, 88% of the variance was explained by the duration of active disease, the number of joints with restricted mobility, the bone area, urinary deoxypyridinoline values, age, weight, and height.

Conclusion

Forty‐one percent of the adolescents with early‐onset JIA had low bone mass >11 years after disease onset. The development of low total‐body BMC was related to the duration of active disease, disease severity, measures of bone resorption, weight, and height.

     

LV systolic impairment in patients with asymptomatic coronary heart disease and type 1 diabetes is related to coronary atherosclerosis, glycaemic control and advanced glycation endproducts

AIMS: To evaluate whether heart failure in type 1 diabetes is linked to poor glycaemic control, coronary atherosclerosis or advanced glycation endproducts (AGEs). METHODS: Twenty six patients with type 1 diabetes (mean duration 32+/-5 years), and 16 age matched controls were recruited. Mean HbA(1c) through 18 years (HbA(1c)18), serum levels of AGEs and coronary atherosclerotic burden (CAB) were determined by IVUS. Peak tissue velocities and strain by tissue Doppler imaging were measured in 12 LV regions as an evaluation of LV function. RESULTS: Systolic tissue velocity was inversely correlated to CAB (r=0.53, p<0.01), to HbA(1c)18 (r=0.46, p<0.05) and to the duration of diabetes (r=0.46, p<0.05). Systolic strain was inversely correlated to HbA(1c)18 (r=0.45, p<0.05), to duration of diabetes (r=0.41, p<0.05), and tended to correlate with AGEs (r=0.37, p=0.07). In multiple regression analyses, CAB and HbA(1c)18 were significant independent predictors for systolic velocity, while AGEs and duration of diabetes were significant predictors of systolic strain. CONCLUSION: LV systolic function was impaired by increasing coronary atherosclerosis and worsening of glycaemic control. AGEs might be another mechanism for the increased risk of heart failure in type 1 diabetes.     

Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly

Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin beta domain (Tbeta). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than Tbeta but binds actin with approximately 10-fold higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation.     

Cold thyroid nodules show a marked increase in proliferation markers.

Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.     

Clinical outcome of patients with Wegener's granulomatosis treated with plasma exchange

We report the clinical course of 29 patients with Wegener's granulomatosis (WG) treated with plasma exchange (PE) in Norway in the period from 1988 to 1999. Median follow-up was 41.5 months. The mean number of exchanges was 8.5 +/- 5.8 (range 2-32). Median serum creatinine concentration was 400 micromol/l (range 90-1,356) and 17 patients were dialysis dependent at presentation. Two- and five-year patient survival was 75 and 71%, respectively, and renal (ESRD-free) survival was 74 and 54%, respectively. Seven (50%) of the 14 patients alive in the dialysis group had discontinued dialysis within the first month, and 6 (50%) of 12 patients alive at follow-up had independent renal function. No patients, however, had normal serum creatinine concentration. Median time until development of ESRD for patients presenting with a need for dialysis was approximately 32 months. The development of ESRD in 79 patients treated with immunosuppression alone was significantly lower, but when adjusted for serum creatinine there was no difference between patients treated with or without PE. Although a considerable fraction of patients with WG and severe renal involvement regain independent renal function, few will have normal serum creatinine concentration at follow-up, despite the addition of PE as adjunctive therapy.     

Lactadherin binds to elastin--a starting point for medin amyloid formation?

Medin amyloid is found in the medial layer of the aorta in almost 100% of the Caucasian population over 50 years of age. The medin fragment is 5.5 kDa and derives from the C2-like domain of the precursor protein lactadherin. We have previously reported immunohistochemical findings showing that medin amyloid co-localizes with elastic fibers of arteries and herein we show that lactadherin also is associated with elastic structures of human aortic material. In addition, results from in vitro binding assays demonstrate that both medin and lactadherin bind to tropoelastin in a concentration-dependent fashion, suggesting that the lactadherin-tropoelastin interaction is mediated via the medin domain. It is possible that lactadherin, which is a cell adhesion protein, in this way connects smooth muscle cells to the elastic fibers of arteries. Given that both medin and lactadherin interact with elastic fibers, elastin is probably an important component in the formation of medin amyloid.     

Effect of exercise training in patients with heart failure: a pilot study on autonomic balance assessed by heart rate variability.

BACKGROUND: Heart rate variability (HRV) is decreased in patients with congestive heart failure (CHF) and is a prognostic marker in this disease. Exercise training is now regarded as an important part of the treatment of patients with CHF, but the effect on HRV and the association between this effect and the effect on neurohormones are not well assessed. METHODS: Heart rate recording was performed in 12 patients with CHF (mean age 67+/-8 years) with CHF NYHA functional class III, before and after 12 weeks of exercise training. The association with exercise capacity and serum levels of atrial natriuretic peptide was assessed. We also evaluated the correlation between HRV and survival at follow-up 87 months later. RESULTS: At baseline there was a significant correlation between mean heart rate and work performed during max cycle test (r=0.650, P=0.022) and the HRV parameter standard deviation normal to normal (SDNN) (r=0.678, P=0.015). After exercise training there was a significant increase in work performed (30.3+/-14.2 versus 38.1+/-14.1 kJ), 6-min walk test (502+/-88 versus 552+/-59 m, P=0.006) and SDNN (117.3+/-40.7 versus 128.6+/-42.3 ms, P=0.028). At 87 months of follow-up, there was a borderline significant difference between survivors and non-survivors. Only the survivors had a significant increase in SDNN after exercise training. CONCLUSION: This pilot study demonstrates an improvement with regard to parameters for HRV after exercise training in patients with CHF. The study suggests that the positive effect of exercise training in patients with CHF involves an attenuation of the reduced HRV response, and that this improvement might have prognostic significance.     

High-sensitivity C-reactive protein is only weakly related to cardiovascular damage after adjustment for traditional cardiovascular risk factors

BACKGROUND: The independent prognostic value of high-sensitivity C-reactive protein (hsCRP) has been questioned, and consequently we decided to investigate whether hsCRP was associated with subclinical cardiovascular (CV) damage independently of traditional CV risk factors. METHODS: In a population-based sample of 2028 apparently healthy individuals without prior stroke or myocardial infarction not receiving any CV, anti-diabetic or lipid-lowering treatment, aged 41, 51, 61 or 71 years, we measured in 1993 serum hsCRP, traditional CV risk factors (lifestyle, metabolic and hemodynamic) and assessed subclinical CV damage [atherosclerotic plaques in the carotid arteries, pulse wave velocity (PWV), urine albumin/creatinine ratio (UACR), left ventricular (LV) mass and ejection fraction]. RESULTS: Adjusting for age and gender in multiple regression analyses, higher log(hsCRP) was associated with higher logPWV (beta = 0.15) and log(left ventricular mass index) (LVMI) (beta = 0.09, both P < 0.001), LV relative wall thickness (beta = 0.07, P < 0.01), logUACR (beta = 0.04, P = 0.06) and more atherosclerotic plaques (beta = 0.06, P < 0.05). However, higher log(hsCRP) was only weakly associated with higher logPWV(beta = 0.06, P < 0.05) and more atherosclerotic plaques (beta = 0.04, P = 0.06) when adjusting for other significant CV risk factors, such as daily smoking (beta = 0.18), female gender (beta = -0.17), older age (beta = 0.11), lower log(high density lipoprotein cholesterol) (beta = -0.11, all P < 0.001); wider waist (beta = 0.17), higher body mass index (beta = 0.14), higher heart rate (beta = 0.06, all P < 0.01); and higher log(plasma glucose) (beta = 0.05, P < 0.05) (adj. R2 = 0.19, P < 0.001). CONCLUSION: After adjustment for traditional CV risk factors hsCRP was only associated with PWV and atherosclerotic plaques, indicating a possible effect of low-grade inflammation on macrovascular damage. The close relationship between traditional CV risk factors and hsCRP suggested that hsCRP was an integrated CV risk marker early in the development of atherosclerosis.