The reaction of the heart to radiation. I. State of the knowledge based on animal experimental studies

The aim of curative tumor therapy is healing without complications. Therefore the avoidance of undesirable side-effects in healthy tissue becomes more important to such a degree as the lifespan can be prolonged by therapy: In this review the experiences to cardiac reactions by ionizing radiations are represented from experiments on animals. The former conception of a marked radioresistance of the heart has to be revised to the hitherto presented investigations. Acute inflammatory reactions and late, often progressive alterations can develop in the heart like in other normal tissue. These late-effects especially are reflected at pericardium, myocardium and vessel system (microvessel system and coronaries) and not rarely cause functional injuries of the tissue. Actual investigations give special attention to pathogenesis of acute radioreaction. It is supposed that their explanation gives a better understanding for the process of independence and progress and with that a possibility for prophylactic or therapeutic measures.     

Toward an implantable artificial heart. Experimental and clinical experience at The Pennsylvania State University

The number of patients who would be candidates for replacement of their failing native heart with an artificial device increases every year. A multidisciplinary group at The Pennsylvania State University is working toward the development of a reliable, totally implantable artificial heart. Initial work resulted in a pneumatic total artificial heart that has performed well in animal implants and has been used clinically in three patients as a temporary bridge to cardiac transplantation. Although pneumatic total artificial hearts have demonstrated utility as temporary mechanical circulatory support devices, attempts at permanent implantation by other groups have been fraught with complications. Because of the suboptimal performance of the pneumatic devices used for permanent implantation, the authors' groups at Penn State is developing n electric motor-driven total artificial heart with encouraging results in calf implants. This artificial heart of the future will use a transcutaneous energy transmission system that will obviate the need for percutaneous lines. Thus, the patient will be provided with as near a normal life-style as possible. At present the technology is at hand to implant an electric blood pump system that should provide a reasonable life-style and function reliably with minimal care. Ongoing cooperative experimental efforts will help to provide the answers necessary to make this system ready for clinical use.     

Radiotracers for cardiac sympathetic innervation: Transport kinetics and binding affinities for the human norepinephrine transporter

IntroductionMost radiotracers for imaging of cardiac sympathetic innervation are substrates of the norepinephrine transporter (NET). The goal of this study was to characterize the NET transport kinetics and binding affinities of several sympathetic nerve radiotracers, including [¹¹C]-(?)-meta-hydroxyephedrine, [¹¹C]-(?)-epinephrine, and a series of [¹¹C]-labeled phenethylguanidines under development in our laboratory. For comparison, the NET transport kinetics and binding affinities of some [³H]-labeled biogenic amines were also determined.MethodsTransport kinetics studies were performed using rat C6 glioma cells stably transfected with the human norepinephrine transporter (C6-hNET cells). For each radiolabeled NET substrate, saturation transport assays with C6-hNET cells measured the Michaelis–Menten transport constants K_m and V_max for NET transport. Competitive inhibition binding assays with homogenized C6-hNET cells and [³H]mazindol provided estimates of binding affinities (K_I) for NET.ResultsK_m, V_max and K_I values were determined for each NET substrate with a high degree of reproducibility. Interestingly, C6-hNET transport rates for ‘tracer concentrations’ of substrate, given by the ratio V_max/K_m, were found to be highly correlated with neuronal transport rates measured previously in isolated rat hearts (r² = 0.96). This suggests that the transport constants K_m and V_max measured using the C6-hNET cells accurately reflect in vivo transport kinetics.ConclusionThe results of these studies show how structural changes in NET substrates influence NET binding and transport constants, providing valuable insights that can be used in the design of new tracers with more optimal kinetics for quantifying regional sympathetic nerve density.     

Quantitative Molecular Imaging of Neuronal Nicotinic Acetylcholine Receptors in the Human Brain with A-85380 Radiotracers

Neuronal nicotinic acetylcholine receptors (nAChRs) have been implicated in a spectrum of cognitive functions as well as psychiatric and neurodegenerative disorders, including tobacco addiction and Alzheimer's Disease. The examination of neuronal nAChRs in living humans is a relatively new field. Researchers have developed brain-imaging radiotracers for nAChRs, with radiolabeled A-85380 compounds having the most widespread use. We provide a brief background on nAChRs, followed by a discussion of the development and application of A-85380 radiotracers in human imaging studies. We describe potential future studies using nicotinic receptor radioligands for the study of tobacco addiction, including the mechanism of action of the smoking-cessation therapy varenicline. Throughout this review, we focus on the significant potential that resides in the identification and quantification of nAChRs in the living human brain.     

Sprains--residual instability of subtalar, Lisfranc joints, and turf toe

Sprains of the hindfoot, midfoot and forefoot are being diagnosed with more regularity in athletes. Each of these injuries can go on to develop chronic instability with associated disability. With early diagnosis and appropriate treatment significant morbidity and loss of playing time can be avoided. Knowledge of the relevant anatomy, mechanism of injury, and available diagnostic tools is essential for making the proper diagnosis. Once the correct diagnosis is made, proper treatment can be implemented to avoid long term complications of instability.     

Calcification of the heart and great vessels.

Calcification of the heart and great vessels is secondary to those diseases which cause a significant alteration of tissue matrix. Metabolic derangements can cause microscopic calcification of heart muscle, but this has not been demonstrated conclusively roentgenographically. The deposition of calcium may follow a single event or be the result of a longstanding process. The etiology and roentgen appearance of calcium deposition in the various tissues which comprise the heart and great vessels are reveiwed. The common as well as the rare cases are considered; if possible, each entity is demonstrated roentgenographically. In addition, an attempt is made to reciew various points of view, which at times are conflicting. The prognostic importance of cardiac, aortic, or pulmonary arterial calcification is underscored whenever possible.     

PET and PET-CT. State of the art and future prospects

Fluoro-deoxyglucose positron emission tomography (FDG PET) enables the in vivo study of tissue metabolism, and thus is able to identify malignant tumours as hypermetabolic lesions by an increase in tracer uptake. Many papers have demonstrated both the relevant impact of FDG PET on staging of many cancers and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation and relapse identification. In particular PET was found useful in identifying lymph nodal and metastatic spread, thus altering patient management in more than 30% of cases. PET images, however, provide limited anatomical data, which in regions such as the head and neck, mediastinum and pelvic cavity is a significant drawback. The exact localization of lesions may also be difficult in some cases on the basis of PET images alone. The introduction of combined PET-computed tomography (PET-CT) scanners enables the almost simultaneous acquisition of transmission and emission images, thus obtaining optimal fusion images in a very short time. PET-CT fusion images enable lesions to be located, reducing false positive studies and increasing accuracy; the overall duration of the examination may also be reduced. On the basis of both literature data and our experience we established the clinical indications when PET-CT may be particularly useful, in comparison with PET alone. It should also be underlined that the use of PET-CT is almost mandatory for new tracers such as 11C-choline and 11C-methionine; these new tracers may be applied for studying tumours not assessable with FDG, such as prostate cancer. In conclusion PET-CT is at present the most advanced method for metabolic imaging, and is capable of precisely localizing and assessing tumours; fusion images reduce false positive and inconclusive studies, thus increasing diagnostic accuracy.     

Computed tomography of the heart.

In an attempt to evaluate the possible usefulness of transmission computed tomography, CT scans of the chest of a series of dead dogs were obtained by means of an EMI body scanner. The sections thus obtained with and without the injection of contrast material reveal a great deal of cardiac morphology. Infarcts of the heart produced prior to scanning were imaged as regions of lower x-ray attenuation. The hearts of a series of live dogs following infarction were imaged by means of a positron emission transverse tomomograph (PETT) following administration of C-palmitate. The images permitted assessment of the relative size of the infarct. The relative advantages of transmission and emission tomography in cardiac visualization are discussed.     

Comparison of in-shoe foot loading patterns on natural grass and synthetic turf

Synthetic playing surfaces with rubber or sand infill are now used on many athletic fields such as soccer, football and rugby. Although these surfaces may come closer to the mechanical characteristics of a true grass playing surface than the older turf designs, their potential effects on lower extremity biomechanics and related injury rates necessitate further study. The purpose of this study was to examine the effects of two surfaces (natural grass versus turf) on in-shoe foot loading patterns during cutting. Seventeen male football players were tested on a slalom course. An in-shoe pressure distribution measurement insole was used in the right shoe (14 stud, molded cleat) of each athlete. Individual cutting steps were extracted from each slalom trial and peak pressure and relative load calculated in nine distinct plantar regions of the foot. The turf condition had significantly higher peak pressures within the central forefoot (turf: 646.6 ± 172.6 kPa, grass: 533.3 ± 143.4 kPa, P = 0.017) and lesser toes (turf: 429.3 ± 200.9 kPa, grass: 348.1 ± 119.0 kPa, P = 0.043) compared to grass. In contrast, the relative load within the medial forefoot (turf: 27.2 ± 5.3%, grass: 30.2 ± 6.6%, P = 0.031) and lateral midfoot (turf: 3.4 ± 1.8%, grass: 4.1 ± 2.3%, P = 0.029) were higher during the grass condition. No differences between the grass and turf were found in maximal effort sprint times performed prior to the testing trials. This study demonstrates that playing surface significantly affects plantar loading during sport related activities. Further epidemiological investigation is warranted to determine the effects of playing surfaces on sport specific injury mechanisms.