35 research outputs found
Serum Levels of Advanced Glycation Endproducts and Other Markers of Protein Damage in Early Diabetic Nephropathy in Type 1 Diabetes
Objective
To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed “early GFR decline”) in patients with type 1 diabetes.
Methods
From the 1st Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8–12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFRCYSTATIN C was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available.
Results
Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK) protein adduct residue and Nω-carboxymethylarginine (CMA) free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both).
Conclusions
Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early renal function decline
Food quality and motivation: A refined low-fat diet induces obesity and impairs performance on a progressive ratio schedule of instrumental lever pressing in rats
IntroductionPurified high-fat diet (HFD) feeding causes deleterious metabolic and cognitive effects when compared with unrefined low-fat diets in rodent models. These effects are often attributed to the diet's high content of fat, while less attention has been paid to other mechanisms associated with the diet's highly refined state. Although the effects of HFD feeding on cognition have been explored, little is known about the impact of refined vs. unrefined food on cognition. We tested the hypothesis that a refined low-fat diet (LFD) increases body weight and adversely affects cognition relative to an unrefined diet.Materials and methodsRats were allowed ad libitum access to unrefined rodent chow (CON, Lab Diets 5001) or a purified low-fat diet (REF, Research Diets D12450B) for 6 months, and body weight and performance on an instrumental lever pressing task were recorded.ResultsAfter six months on their respective diets, group REF gained significantly more weight than group CON. REF rats made significantly fewer lever presses and exhibited dramatically lower breaking points than CON rats for sucrose and water reinforcement, indicating a chronic reduction of motivation for instrumental performance. Switching the rats' diet for 9 days had no effect on these measures.ConclusionsDiet-induced obesity produces a substantial deficit in motivated behavior in rats, independent of dietary fat content. This holds implications for an association between obesity and motivation. Specifically, behavioral traits comorbid with obesity, such as depression and fatigue, may be effects of obesity rather than contributing causes. To the degree that refined foods contribute to obesity, as demonstrated in our study, they may play a significant contributing role to other behavioral and cognitive disorders
CryoLife-O'Brien Stentless Valve: 10-Year Results of 402 Implants
Background This truly stentless porcine valve is composite, without Dacron and implanted supra-annularly. Ten year analysis with magnetic resonance imaging is presented. Methods From 1992 to 2002, 402 patients (mean 73.5 yrs) had aortic valve replacement. Associated procedures were required in 252 patients (63%). Serial echoes provided 1340 studies. Clinical follow-up was 100%. Magnetic Resonance Imaging focused on aortic annulus extensibility. Results The 30 day mortality was 0.99% (4 deaths). Morbidity comprised (a) thromboembolism (40 patients including 18 patients with permanent strokes); (b) endocarditis (nine patients); (c) re-operation (nine patients) - peri-prosthetic leak (2), endocarditis (5), technical needle damage (1) and structural degeneration (1). Of 402 valves over 10 years, five valves were explanted, one only for structural failure. Except for endocarditis (2), no late deaths (69 pts, 1.5 months – 5.7 yrs) were valve related. Echocardiography demonstrated low gradients with good orifice areas, excellent ventricular regression (p = 0.0001 pre and post-operative comparisons) and late incompetence - mild (45 pts) and moderate (nine pts). No living patient has severe incompetence. Magnetic Resonance Imaging demonstrated the annulus ‘expanding and relaxing’ throughout the cardiac cycle, the mean increase in cross-sectional area being 37%, resembling normal aortic root dynamics. Conclusion Elderly patients received this hemodynamically acceptable valve with its simple, supra-annular implantation and satisfactory mid-term morbid-free lifestyle to 10 years maximum follow-up. With only one structural failure, restoration of valve annular extensibility may have a favourable influence on long-term durability
How to do Safe Sternal Reentry and the Risk Factors of Redo Cardiac Surgery: A 21 Year Review with Zero Major Cardiac Injury
Objectives: Resternotomy is a common part of cardiac surgical practice. Associated with resternotomy are the risks of cardiac injury and catastrophic hemorrhage and the subsequent elevated morbidity and mortality in the operating room or during the postoperative period. The technique of direct vision resternotomy is safe and has fewer, if any, serious cardiac injuries. The technique, the reduced need for groin cannulation and the overall low operative mortality and morbidity are the focus of this restrospective analysis. Methods: The records of 495 patients undergoing 546 resternotomies over a 21-year period to January 2000 were reviewed. All consecutive reoperations by the one surgeon comprised patients over the age of 20 at first resternotomy: M:F 343:203, mean age 57 years (range 20 to 85, median age 60). The mean NYHA grade was 2.3 [with 67 patients (1), 273 (11),159 (111), 43 (IV), and 4 (V classification)] with elective reoperation in 94.6%. Cardiac injury was graded into five groups and the incidence and reasons for groin cannulation estimated. The morbidity and mortality as a result of the reoperation and resternotomy were assessed. Results: The hospital/30 day mortality was 2.9% (95% Cl: 1.6%-4.4%) (16 deaths) over the 21 years. First (481), second (53), and third (12) resternotomies produced 307 uncomplicated technical reopenings, 203 slower but uncomplicated procedures, 9 minor superficial cardiac lacerations, and no moderate or severe cardiac injuries. Direct vision resternotomy is crystalized into the principle that only adhesions that are visualized from below are divided and only sternal bone that is freed of adhesions is sewn. Groin exposure was never performed prophylactically for resternotomy. Fourteen patients (2.6%) had such cannulation for aortic dissection/aneurysm (9 patients), excessive sternal adherence of cardiac structures (3 patients), presurgery cardiac arrest (1 patient), and high aortic cannulation desired and not possible (1 patient). The average postop blood loss was 594 mL (95% CI:558-631) in the first 12 hours. The need to return to the operating room for control of excessive bleeding was 2% (11 patients). Blood transfusion was given in 65% of the resternotomy procedures over the 21 years (mean 854 mL 95% Cl 765-945 mL) and 41% over the last 5 years. Conclusions: The technique of direct vision resternotomy has been associated with zero moderate or major cardiac injury/catastrophic hemorrhage at reoperation. Few patients have required groin cannulation. In the postoperative period, there was acceptable blood loss, transfusion rates, reduced morbidity, and moderate low mortality for this potentially high risk group
Perforated mitral valve annular phlegmon with ventriculo-atrial fistula
Herein we describe a case of perforated mitral valve annular abscess/phlegmon that presented as a new pan-systolic murmur in the setting of hallux osteomyelitis requiring amputation. We discuss the investigations, imaging and complex management challenges arising from this rare condition and the importance of considering a diagnosis of infective endocarditis in patients with a new cardiac murmur
Vascular remodeling in the internal mammary artery graft and association with in situ endothelin-1 and receptor expression
Background - The vasoconstricting peptide endothelin-1 (ET-1) has been associated with atherosclerotic cardiovascular disease, vascular smooth muscle cell (VSMC) growth stimulation, and intimal thickening. ET-1 binds 2 receptor subtypes, endothelin A and B, and the ETA receptor mediates vasoconstriction and VSMC growth. This study aims to quantitatively assess arterial remodeling variables and compare them with changes in ET-1, ETA, and ETB expression in the internal mammary artery (IMA)