Kardiale Manifestationen der HIV-Infektion

Zusammenfassung. Die Infektion mit dem humanen Immundefizienzvirus (HIV) betrifft nicht nur das Immunsystem des menschlichen Organismus, sondern schließt vielmehr eine Reihe weiterer Organsysteme mit ein. Es wird angenommen, dass bei 5-15% der HIV-positiven Patienten kardiale Manifestationen auftreten. Zu den häufigsten HIV-assoziierten kardialen Manifestationen gehören der Perikarderguss und die chronisch aktive, fokale oder diffuse Myokarditis. Endokardiale Manifestationen bei HIV-positiven Patienten treten in Form der infektiösen Endokarditis und der nichtbakteriellen thrombotischen Endokarditis auf. In der Regel weisen HIV-assoziierte kardiale Manifestationen einen langsam progredienten Krankheitsverlauf auf. Komplikationen sind Folge eines langfristig unentdeckten Fortschreitens der Erkrankung, aber auch schnell progredienter Verlaufsformen. Aufgrund der Vielzahl HIV-assoziierter kardialer Manifestationen und deren möglicher Komplikationen ist daher neben der Früherkennung ein effektives diagnostisches und therapeutisches Vorgehen erforderlich. Seit Einführung der Proteaseinhibitoren in den 90er Jahren und der Anwendung der hochaktiven antiretroviralen Kombinationstherapie (HAART) konnten sowohl Mortalität als auch Morbidität der HIV-Infektion deutlich gesenkt werden. Die Auswirkungen der HAART auf das kardiovaskuläre System sind bisher nur in Ansätzen bekannt. Als Nebenwirkungen wurden metabolische Veränderungen in Form von Hyperlipoproteinämie und Insulinresistenz bei einer Vielzahl HIV-positiver Patienten beobachtet. Es kann davon ausgegangen werden, dass durch den Anstieg der kardiovaskulären Risikofaktoren unter der HAART in den nächsten Jahren eine erhöhte Rate kardialer Erkrankungen bei HIV-positiven Patienten auftreten wird. In dem vorliegenden Übersichtsartikel wird ein Überblick über die häufigsten kardialen Erkrankungen bei HIV-Infektionen gegeben. Zusätzlich werden Vorschläge zu Diagnostik und Therapie unterbreitet und eine Einschätzung über Veränderungen der HIV-assoziierten kardialen Manifestationen nach Einführung der HAART vorgenommen. Abstract. The human immunodeficiency virus (HIV) does not only affect the immune system. Other organs including the cardiovascular system are influenced by the HIV as well. Most common HIV-associated cardiac manifestations are pericardial effusion and chronic active, focal or diffuse myocarditis. In addition to peri- and myocardial disease, endocardiac manifestations occur as infective endocarditis and nonbacterial thrombotic endocarditis in HIV-infected patients. Although most of the cardiac manifestations associated with HIV-infection exhibit a slow progression, rapid courses may lead to fatal complications. Early screening of HIV-infected patients will identify the potentially fatal complications of HIV disease and permit efficient treatment. The use of highly active antiretroviral therapy (HAART) significantly reduced the mortality and morbidity of HIV-infected patients. However, the impact that HAART will have on the incidence and prevalence of cardiac complications in HIV-infected patients is still unknown. It can be predicted, that the long-term viral infection and the increase of cardiovascular risk factors by HAART will probably lead to an increased prevalence of HIV-infected individuals with cardiac complications in the next decade. The present review describes the most frequent HIV-associated cardiac manifestations including diagnostic and therapeutic perspectives.     

Measuring behaviour: The tools and the strategies

Animal behaviour can be viewed as a stream of elements, which, once accurately described, can be counted and timed. Data acquisition techniques and tools are reviewed, and some strategies for collection and analysis of data using PC computers are suggested. Automated instruments are not satisfactory for the study of complex behaviour and as such systemic observation remains irreplaceable. IBM PC-type computers, with a wide range of analytical software (e.g., spreadsheets, statistical packages, technical graphics), are practical for data acquisition. Several systems which can satisfy different applications are reviewed. Some systems can communicate with a videorecorder, a facility which remarkably increases the accuracy of measurement; this is essential for meaningful analyses of the internal structure of behavioural streams (sequences, time patterns) or communication processes. The power of new tools enables behavioural measurement with the necessary complexity to allow a whole new set of questions to be addressed. However, it also increases demands for meaningful content and analysis of data.     

Transneuronal degeneration of thalamic neurons following deafferentation: quantitative studies using [3H]thymidine autoradiography.

Transneuronal degeneration of thalamic neurons following partial deafferentation was studied using [3H]thymidine autoradiography. Timed-pregnant female Sprague-Dawley rats received systemic injections of [3H]thymidine on embryonic day (E) 13, 14 and/or 15. On the day of birth, pups were anesthetized by hypothermia and subjected to unilateral enucleation, unilateral removal of the inferior colliculus or sham lesion. Animals were sacrificed on postnatal day 10 or 30 and the brains processed for autoradiography. Material from sham-lesioned animals demonstrates that neurons destined for the dorsal lateral geniculate nucleus (LGd) undergo final mitoses on E13, 14 and 15. Neurons in the ventral medial geniculate nucleus (MGv) undergo final mitoses on E13 and 14. Thirty days following neonatal unilateral eye removal, the contralateral LGd displays a loss of approximately 30-35% of [3H]thymidine labeled neurons. Neonatal unilateral removal of the inferior colliculus results in a loss of approximately 30-40% of labeled neurons in MGv. For both LGd and MGv, shorter survival times reveal less severe cell loss. Late generated (E15) LGd neurons show less severe loss following enucleation than do earlier generated neurons. These results document the degree of cell loss in sensory thalamic nuclei following deafferentation and demonstrate that [3H]thymidine autoradiography provides a useful quantitative method for assessing anterograde transneuronal cell loss in targeted populations of neurons in the developing central nervous system.     

Wall-thickness and midwall-radius variations in ventricular mechanics.

A fluid-fiber-collagen stress tensor is used to describe the rheology of the left ventricle of the heart. Linear theory is used to find the equilibrium solutions for the end-diastolic and end-systolic states of general axisymmetric shapes that are small perturbations of a thick-walled finite cylinder. The general problem can be studied by superposing the effects of variable midwall radius but constant wall thickness with those of variable wall thickness but constant midwall radius. A Fourier series representation is used to describe the midwall radius and thickness functions. Numerical calculations are performed to determine the deformed geometry and spatial distributions of tissue pressure, stresses, and fiber strains. The calculations proved to be highly accurate when compared to an analytical solution obtained for the special case of no fibers. The results show significant longitudinal differences when compared to results for the cylindrical geometry, with more sensitivity to variation in wall thickness than to variation in midwall radius.     

Ultrastructural observations of organelle accumulation in the equine recurrent laryngeal nerve

Summary The left recurrent laryngeal nerves from five horses with sub-clinical neuropathy were examined by light and electron microscopy in a study designed to examine accumulation of axonal organelles at paranodal and internodal locations. Transverse sections of the nerve showed scattered fibres with split myelin sheaths and axonal accumulation of organelles. On longitudinal sections these collections were seen to result from an axonal outpouching in which dense lamellar bodies and mitochondria had accumulated. These paranodal collections, which could be found on both sides of the node, were often associated with infoldings of the terminal loops of myelin and with occasional paranodal demyelination. The fact that many of the organelles in the outpouches were lysosomal in nature was confirmed by their positive staining for cathepsin D activity. Longitudinal sections demonstrated a number of axons which were swollen over a long distance and which contained focal accumulations of similar organelles. In places, however, there was a clear separation between these organelles and the cytoskeletal proteins. In each case these swollen axons were surrounded by Schwann cell nuclei and their processes, forming well-ordered onion bulbs. The possibility that these two types of changes, i.e. the paranodal accumulations and the axonal swellings could result from a disturbance in axonal transport in this distal axonopathy is discussed.