Chronische Transplantatdysfunktion

Chronic transplant dysfunction is a complex dynamic pathogenic process. Clinically, a decrease in glomerular filtration rate (GFR) becomes apparent leading to chronic renal insufficiency and dialysis or death from cardiovascular events. Chronic transplant dysfunction can develop into a chronic alIograft nephropathy (CAN) as a specific entity with dynamic progression. CAN includes a collection of immunologic and non-immunologic factors, rejection, ischemia time, donor and recipient characteristics and toxicity of calcineurin inhibitors. Despite improvements in immunosuppression, the long-range prognosis of renal allografts has not improved. Whether modern immunosuppressive concepts with reduction or avoidance of calcineurin inhibitors and a therapy based on antimetabolites, such as mycophenolate or mTOR-inhibitors could lead to a prolongation of transplant survival, remains to be seen.     

Growth of children from 0-5 years: with special reference to mother's smoking in pregnancy

A cohort of 1163 pregnant women in two small towns in South Wales, UK, was identified and followed until the children born to them were five years of age. Growth in these children is described and a number of determinants identified. Social-class differences were very small at birth but differences in height became clear by the age of two years and in head circumference before this. In height the differences were largely accounted for by greater growth in social class I, but there was a gradient in head circumference throughout all the social classes. The social class effects gradually increased as the children became older. Parity of the mothers had a small effect on size at birth but age of the mother had no effect once parity was allowed for. Data on illnesses in the children were collected but no effect on growth could be detected. By far the most important determinant of growth which could be controlled is maternal smoking. About 40% of the women smoked, about 17% heavily (15 or more cigarettes per day) and the prevalence of smoking altered little during pregnancy. There was a graded effect of smoking on growth up to a 9% deficit in birth-weight, a 2% deficit in length at birth and a 1.5% deficit in head circumference in the babies born to the mothers who smoked most heavily (25 or more cigarettes per day) compared with non-smokers. There effects decreased with age but there were still residual effects at age five years.     

Multimodal—was ist das überhaupt?

In chronic pain syndromes multimodal treatment has proved its efficacy. However, multimodal treatment does not mean randomly combining different interventions in a potpourri of methods. Multimodal treatment must closely follow a well-proved conceptual framework. Those concepts may be well illustrated by therapy of back pain. The most elaborate model for understanding the transition from acute to chronic pain is fear avoidance. Based on this model chronic pain status is understood as a learned consequence, which resulted from patients’ anxious avoidance of body movements. In these cases, treatment of a physical pathology is not the main aim of therapy but rather functional restoration. Those multimodal programs meanwhile have demonstrated their effectiveness. However, good results not only depend on recognition of imperative elements in therapy but also on adhering to essential principles (avoidance of negative anticipation, adequate information with assurance techniques, no training of avoidance, recognition of elements of fear therapy).     

Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Meningitis

The most frequent pathogens causing bacterial meningitis in Germany are Neisseria meningitidis, Streptococcus pneumoniae, Borrelia burgdorferi, Listeria monocytogenes and staphylococci. Since immunization against Haemophilus influenzae has become a routine vaccination procedure, this pathogen no longer plays a significant role in the etiology of bacterial meningitis. A number of pilot studies have indicated that selected PCR methods most probably represent the future etiological diagnosis of bacterial meningitis. The easiest and most rapid diagnostic method is, however, still a simple gram stain preparation. In fatal cases that ran a peracute course, especially in the Waterhouse-Friderichsen syndrome, only increased congestion of the surface of the brain is detectable at autopsy. In such cases, there is hardly any histological evidence of an inflammatory reaction of the leptomeninges. In cases of purulent meningitis, in addition to the typical infiltration of the subarachnoid space with abundant granulocytes, after some days of illness there is a wide-spread histomorphological picture of pathological alterations with fibrinoid vessel wall necroses, thromboses, ventriculitis, infarctions as well as venous and arterial vasculitis. The breakdown of the integrity of the blood-brain-barrier in bacterial meningitis is obviously due to a separation of intercellular tight junctions of the endothelium of the capillaries of the leptomeninges. The cause of death in meningitis, depending on the severity and duration of a concomitant sepsis, is an increase in intracranial pressure that leads to a circulus vitiosus (via a reduced central perfusion associated with metabolic acidosis) with cerebral vasodilatation. This is followed by an additional rise of intracranial pressure and finally a reduced cerebral blood supply and central dysregulation. The medico-legal expert is occasionally confronted with this topic against the background of a possible misjudgement of the disease due to insufficient diagnostics or delayed diagnosis and in the light of a posttraumatic or nosocomial origin of the illness.     

Sonographische Messung der Fruchtwassermenge

Ohne Zusammenfassung