Clinical aspects of induced hypothermia in full term neonates with perinatal asphyxia

Moderate hypothermia is a novel neuroprotective therapy for full term neonates with severe perinatal asphyxia. Although the therapy appears to be safe, admission to a level III neonatal intensive care unit of these patients is justified. Potential complications include hypotension, tube obstruction due to sticky secretions, severe bradycardia, and thrombocytopenia. Furthermore, doses of commonly used drugs such as sedatives, anticonvulsants and antibiotics should be adjusted during hypothermia and on rewarming, and should be monitored carefully. Further studies aiming at optimizing onset, duration, and depth of hypothermia in neonates are necessary. Combination of hypothermia with drugs may further improve neuroprotection in asphyxiated full term neonates.     

Progress in therapeutic antisense applications for neuromuscular disorders

Neuromuscular disorders are a frequent cause of chronic disability in man. They often result from mutations in single genes and are thus, in principle, well suited for gene therapy. However, the tissues involved (muscle and the central nervous system) are post-mitotic, which poses a challenge for most viral vectors. In some cases, alternative approaches may use small molecules, for example, antisense oligonucleotides (AONs). These do not deliver a new gene, but rather modulate existing gene products or alter the utilization of pathways. For Duchenne muscular dystrophy, this approach is in early phase clinical trials, and for two other common neuromuscular disorders (spinal muscular atrophy and myotonic dystrophy), significant preclinical advances have recently been made.     

Rhizomelic Chondrodysplasia Punctata and cardiac pathology

Tijdschrift voor Kindergeneeskunde -     

The dialytic management of acute renal failure in the elderly

In this article the different dialysis strategies in the management of acute renal failure (ARF) in the elderly are discussed. Although peritoneal dialysis (PD) offers some theoretical advantages, there are several medical and technical reasons why it is currently less frequently used. The choice between intermittent hemodialysis (HD) and continuous renal replacement therapy (CRRT) is determined by a number of considerations, the most important ones being hemodynamic stability, the need for hyperalimentation and/or ultrafiltration, and the local experience with one or both techniques. Some recent studies with CRRT in elderly ARF patients describe favorable results. Slow extended daily dialysis (SLEDD) modalities may be particularly indicated in elderly, critically ill ARF patients because these techniques combine the advantages of both CRRT and HD. Finally, the importance of the biocompatibility of dialysis membranes is discussed. Although there are a number of theoretical arguments to use biocompatible membranes, this opinion is not always supported by the results of recent comparative studies. It is the opinion of the authors that all dialysis strategies should be mastered and utilized for appropriate indications in elderly ARF patients.     

A physiological threshold for protection against menadione toxicity by human NAD(P)H:quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells

NAD(P)H:quinone oxidoreductase 1 (NQO1) has often been suggested to be involved in cancer prevention by means of detoxification of electrophilic quinones. In the present study, a series of Chinese hamster ovary (CHO) cell lines expressing various elevated levels of human NQO1 were generated by stable transfection. The level of NQO1 over-expression ranged from 14 to 29 times the NQO1 activity in the wild-type CHO cells. This panel of cell lines, allowed investigation of the protective role of NQO1 in quinone cytotoxicity. It could be demonstrated that menadione toxicity was significantly reduced in all NQO1-transfected CHO clones compared to the wild-type cells, but the clones did not show differences in their level of protection against menadione. This observation pointed at a critical threshold concentration of NQO1 above which a further increase does not provide further protection against quinone cytotoxicity. Additional studies in which the NQO1 activity was inhibited by dicoumarol showed that only dicoumarol concentrations of about five times the EC(50) for NQO1 inhibition were able to reduce NQO1 levels below the apparent threshold, making the cells more sensitive. The level of this threshold was estimated to be in the range of base line NQO1 activities observed in several tissues and species. Thus, the results of the present study indicate that beneficial effects of NQO1 induction by, for example, cruciferous vegetables might be absent or present depending on the NQO1 activity threshold for optimal protection and the basal level of NQO1 expression in the tissue and species of interest.     

Expectations of treatment and satisfaction with dentofacial appearance in orthodontic patients.

The aim of this study was to investigate correlations between satisfaction with dental and facial appearance and expectations of orthodontic treatment. The effects of sex and age on these variables were also explored. A sample of 154 patients who applied for orthodontic treatment at the Academic Centre of Dentistry Amsterdam, The Netherlands, completed 2 questionnaires, containing 16 items on satisfaction with facial appearance and 23 items on expectations of orthodontic treatment. First, the structure of the questionnaires was analyzed. Next, correlations between patients' expectations, satisfaction with facial appearance, age, and sex were examined. A multiple regression analysis was used to estimate the effect of the initial facial satisfaction on expectations of orthodontic treatment. Principal components analysis of the questionnaire about expectations showed 4 factors with an Eigenvalue greater than 1, accounting for 72% of the total variance. These were defined as "general well-being," "self-image/appearance," "future dental health," and "oral function." We found that "satisfaction with facial appearance" could be divided into 2 factors, each with an Eigenvalue greater than 1, accounting for 64% of the total variance. These were interpreted as "general facial appearance" and "dental appearance." Significant correlations were found between satisfaction with dental appearance and patients' expectations. These correlations were invariant over gender, but not over age. It was concluded that satisfaction with dental appearance is a significant predictor of orthodontic patients' expectations of treatment.     

Regulated expression of alpha-1 adrenergic receptors in the immune system

The catecholamines norepinephrine and epinephrine are used by the sympathetic nervous system to communicate with other organ systems, including the immune system. Adrenergic receptors on target cells bind these catecholamines and modulate the activity of the target cell. The beta 2-adrenergic receptor is the most abundantly expressed and best studied adrenergic receptor in the immune system. Here, I summarize data from our own laboratory and from others on the expression and possible function of alpha 1-adrenergic receptors in the immune system. alpha 1-Adrenergic receptor expression in the immune system can be regulated by glucocorticoids, by beta 2-adrenergic agonists, and by cytokines. In addition, the possible pathophysiological implications of the expression of alpha 1-adrenergic receptors on immune cells from arthritis patients are discussed.