Integrins αvβ3 and αvβ5 mediate VSMC migration and are elevated during neointima formation in the rat aorta

Neointima formation involves tissue expression of matrix proteins and growth factors. The role of α_vβ₃, but not α_vβ₅ integrin in vascular cells has been sufficiently investigated. The aim of the present study was to determine and compare the function of α_vβ₃ and α_vβ₅ integrins in rat aortic (RASMC) and human coronary vascular smooth muscle cells (HCSMC) and to characterize their expression accompanying neointima formation in vivo. RASMC and HCSMC express α_vβ₃ and α_vβ₅ integrin subunits. The α_vβ₅ integrin predominantly mediated adhesion of RASMCs to vitronectin and spreading on vitronectin via RGD-binding sequences. In contrast, the α_vβ₃ integrin did not contribute to the adhesion and spreading on fibronectin, vitronectin, gelatin or collagen I coated layers. PDGF-directed migration through gelatin coated membranes involved both α_vβ₃ and α_vβ₅ integrins. Selective blocking antibodies for α_vβ₃ and α_vβ₅ inhibited migration of RASMC and HCSMC by more than 60% (p < 0.01). Integrin expression was studied in vivo in thoracic aorta of Sprague Dawley rats before and after balloon injury. In situ hybridization demonstrated low signals for α_vβ₃ and β₅ mRNA in uninjuried aorta, which increased significantly at 14 days, localized predominantly in the neointima. Northern analysis of aorta after 14 days of injury also demonstrated an upregulation of α_vβ₃ and β₅ mRNA compared to uninjured aorta. Consistent with the increase in message levels, increased inegrin protein expression was seen in the neointima after 7 and 14 days. This study provides evidence that α_vβ₃ and α_vβ₅ are elevated during neointima formation in the rat and indicates a novel role for α_vβ₅ participating in mechanisms regulating smooth muscle cell migration. Received: 30 May 2000, Returned for revision: 10 July 2000, Revision received: 27 July 2000, Accepted: 16 August 2000     

Alignment for total knee replacement: a comparison of kinematic axis versus mechanical axis techniques. A cadaver study

Purpose

Standard instrumentation tries to reproduce mechanical axes based on mechanical alignment (MA) guides. A kinematic alignment (KA) technique derives its plan from pre-operative MRI-measurements. This matched-pair cadaveric study compared the resulting postoperative alignments.

Methods

A prospective series of 12 torsos were acquired for a total of 24 limb specimens including intact pelvises, femoral heads, knees, and ankles.The cadavers received MRI scans to manufacture the kinematic alignment cutting guides. Two investigating surgeons performed total knee arthroplasties on randomly chosen sides using MA instruments. On the contralateral sides, KA cutting guides were used. A navigation system was used to measure final alignment.

Results

The overall alignment showed no significant differences between the systems. In the MA group the differences between the planned and the final implantation regarding overall limb alignment ranged between 0.2° and 6.2°. In the KA group the differences between the planned and final implantation regarding overall limb alignment ranged between 0.3° and 9.1°. The differences of the deviation from plan for overall limb alignment showed no significant differences between the methods.

Conclusions

The different alignment strategies resulted in variations of the combinations of the three-dimensional component position on the femur and the tibia. However, the legs were aligned within comparable range for both chosen techniques.     

Emerging Concepts for Myocardial Late Gadolinium Enhancement MRI

Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments.     

Magnetic resonance imaging of aneurysms and thrombi

This is a report of the first systematic investigation of the qualitative and quantitative diagnosis of aneurysms in the regions of the left ventricle and thoracic and abdominal aorta plus proof of intracavitary thrombi in the heart and the aorta, as well as aneurysms in the superior and inferior vena cava. For diagnosis of the heart, ECG gating is an absolute necessity, but for the analysis of abdominal aortic aneurysms it only leads to a considerable improvement of the spatial resolution. For differential diagnosis of the blood flow and intracavitary clots in the heart and the aorta, use of a second or even multiple echoes is needed. Also, digital subtraction between the first and second echoes (magnetic resonance digital subtraction) can assist in assessing flow. When dissecting aortic aneurysm is suspected and in cases when risk of perforation of ventricular and aortic aneurysms is present, MR offers particular advantages, since it is noninvasive and few scans can provide all the information that is required.     

Fruktose vs. Glukose in der total parenteralen Ernährung kritisch kranker Patienten

Parenteral nutrition required following surgery or injury should not only meet post-aggression caloric requirements but also match the specific metabolic needs so as not to worsen the metabolic disruptions already present in this situation. The primary objective of parenteral nutrition is body protein maintenance or restoration by reduction of protein catabolism or promotion of protein synthesis or both. Whether all parenteral energy donors, i.e., glucose, fructose, other polyols, and lipid emulsions, are equally capable of achieving this objective continues to be a controversial issue. The objective of the present study was to answer the following questions: (1) Do glucose and fructose differ in their effects on the metabolic changes seen following surgery or injury, the changes in glucose metabolism in particular? (2) Can the observation of poorer glucose utilization in the presence of lipids be confirmed in ICU patients? Patients, materials and methods. A prospective, randomized clinical trial has been conducted in 20 aseptic surgical ICU patients to generate an objective database along these lines by performing a detailed analysis of the metabolic responses to different parenteral nutrition protocols. The effects of a glucose solution+lipid emulsion regimen vs fructose solution+lipid emulsion regimen on a number of carbohydrate and lipid metabolism variables were evaluated for an isocaloric (carbohydrates: 0.25?g/kg body weight/h; lipids: 0.166?g/kg body weight/h) and isonitrogenous (amino acids: 0.0625?g/kg body weight/h) total nutrient supply over a 10-h study period. Results. A significantly smaller rise in blood glucose concentrations (increase from baseline: glucose+lipids P<0.001 vs fructose+lipids n.s.) suggested that fructose had a small effect, if any at all, on glucose metabolism. Serum insulin activity showed significant differences as a function of carbohydrate regimen, i.e. infusion of fructose instead of glucose produced a less pronounced increase in insulin activity (increase from baseline: glucose+lipids P<0.001 vs fructose+lipids P<0.01). Impairment of glucose utilization by concomitant administration of lipids was observed neither in patients who first received glucose nor in those who first received fructose. Conclusions. As demonstrated, parenteral fructose, unlike parenteral glucose, has a significantly less adverse impact than glucose on the glucose balance, which is disrupted initially in the post-aggression state. In addition, the less pronounced increase in insulin activity during fructose infusion than during glucose infusion can be assumed to facilitate mobilization of endogenous lipid stores and lipid oxidation. Earlier workers pointed out that any rise in free fatty acid and ketone body concentrations in the serum produces inhibition of muscular glucose uptake and oxidation, and of glycolysis. These findings were recorded in a rat model and could not be confirmed in our post-aggression state patients receiving lipid doses commensurate with the usual clinical infusion rates. The serious complications that can result from hereditary fructose intolerance are completely avoidable if a careful patient history is taken before the first parenteral use of fructose. If the patient or family members and close friends, are simply asked whether he/she can tolerate fruit and sweet dishes, hereditary fructose intolerance can be ruled out beyond all reasonable doubt. Only in the extremely rare situations in which it is not possible to question either the patient or any significant other, a test dose will have to be administered to exclude fructose intolerance. The benefits of fructose-specific metabolic effects reported in the literature and corroborated by the results of our own study suggest that fructose is an important nutrient that contributes to metabolic stabilization, especially in the post-aggression phase and in septic patients. Hyperglycaemic states are largely prevented, and fewer patients require exogenous insulin, thus avoiding the frequently underestimated risk of hypoglycaemic states.     

Quantification of focal dystonia in pianists using scale analysis.

Focal dystonia in pianists is a task-specific movement disorder that causes loss of pianistic skills and provokes irregularities in playing. So far, no method has been available for objective quantification of the disorder. Eight professional pianists with focal dystonia and eight healthy professional pianists matched by age, gender, and handedness were examined, using a newly developed MIDI-based Scale Analysis as well as the Arm Dystonia Disability Scale (ADDS). Key velocities and timing parameters were analyzed. In 5 pianists with dystonia, follow-up examinations were carried out after treatment with botulinum toxin-A. In affected hands, significantly higher mean standard deviations of timing parameters were seen compared with healthy reference hands. After treatment with botulinum toxin-A, significant improvements in performance parameters were monitored by Scale Analysis. Mean standard deviations of inter-onset intervals correlated with ADDS scores. We conclude that Scale Analysis is an effective and precise tool for quantification of focal dystonia in pianists and provides fine resolution. It is independent of rating methods and allows reliable follow-up examinations during treatment.