The whole leg radiograph

The whole leg radiograph (WLR), the standard technique for determining axial alignment, is usually taken in a standing position, although some prefer the supine position. To determine the difference between these two positions, we performed a standing and a supine WLR in 20 patients with a varus alignment. We found an average of 2 degrees more varus deviation in the standing position than in the supine position.     

Sumatriptan nasal spray in the acute treatment of migraine in adolescents and children

About 4-10% of children and adolescents suffer from migraine. In the last few years, several studies have been performed to assess the efficacy and safety of triptans for the acute treatment of migraine in children and adolescents. Only sumatriptan nasal spray has been approved for the treatment of acute migraine with or without aura in adolescents aged 12-17 years in Europe. This review describes the results of the studies with sumatriptan nasal spray that have been performed in children and adolescents, including a study performed in the Netherlands.     

Dermatitis in bulb growers

A damaged skin forms a health hazard in flower-bulb growers as it enables higher permeation rates For pesticides than normal skin. Therefore, an investigation was performed into the skin condition of 103 bulb growers and 49 controls. Contact dermatitis of the hands was of the same order (11 and 10%) in both groups. However, minor signs of dermatitis were seen more often in bulb growers (30 versus 8%, p <0.05). Most growers had contact with narcissus sap during the investigation. This irritant sap, as well as many other skin contacts with irritants such as hyacinth dust and pesticides, seemed to be responsible for many skin complaints. Contact serialization was suspected in 19 growers and 3 controls. Patch tests showed that contact sensitization existed to pesticides in probably 10, and to flower-bulb extracts in 4 growers. Reactions to propachlor were not regarded as very reliable as the test concentration seemed to be marginally irritant. There were only a few allergic reactions to narcissus (3) and tulip (2) and none to hyacinth. This investigation showed that minor irritant contact dermatitis was frequent in bulb growers, and indicated that contact sensitization to pesticides and bulbs seemed to be a less frequent but important cause of dermatitis.     

Influence of CD28 co-stimulation on cytokine production is mainly regulated via interleukin-2.

Interaction of CD28 with its ligand B7 plays an important role in the initiation of immune responses. The co-stimulatory signal generated by cross-linking of CD28 molecules results in enhanced T-cell proliferation and augmentation of cytokine production. In particular, mRNA levels of T-helper 1 (Th1)-type cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are reported to be strongly increased. We investigated the effect of CD28 co-stimulation on the production of Th2-type cytokines. CD28 mAb induced a strong augmentation of IL-2 secretion in activated T-cell clones. Production of IFN-gamma was also enhanced, but the increase in IL-4 secretion was generally moderate. Augmentation of IL-4 production by CD28 was most pronounced in clones that produced low amounts of IL-2, compared to clones producing high levels of IL-2. It was found that the up-regulation of IL-4 by CD28 co-stimulation was mainly controlled indirectly via an increase of IL-2. Some clones could produce IL-4 in an IL-2-independent manner; in these situations CD28 co-stimulation had no augmenting effect on the production of IL-4. The secretion of IL-4 by peripheral blood CD4+ T cells, that were activated with B7-expressing transfectants, was also found to be dependent on IL-2. Finally, Northern blot analysis confirmed that co-stimulation of CD28 primarily affected IL-2 production, and that inhibition of IL-2/IL-2 receptor interaction abolished the augmenting action of CD28 monoclonal antibody on the production of the Th2-type cytokines IL-4, IL-5 and IL-10 and of the Th1 cytokine IFN-gamma.     

SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis

Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms.     

What triggers catch-up saccades during visual tracking?

When tracking moving visual stimuli, primates orient their visual axis by combining two kinds of eye movements, smooth pursuit and saccades, that have very different dynamics. Yet, the mechanisms that govern the decision to switch from one type of eye movement to the other are still poorly understood, even though they could bring a significant contribution to the understanding of how the CNS combines different kinds of control strategies to achieve a common motor and sensory goal. In this study, we investigated the oculomotor responses to a large range of different combinations of position error and velocity error during visual tracking of moving stimuli in humans. We found that the oculomotor system uses a prediction of the time at which the eye trajectory will cross the target, defined as the "eye crossing time" (T(XE)). The eye crossing time, which depends on both position error and velocity error, is the criterion used to switch between smooth and saccadic pursuit, i.e., to trigger catch-up saccades. On average, for T(XE) between 40 and 180 ms, no saccade is triggered and target tracking remains purely smooth. Conversely, when T(XE) becomes smaller than 40 ms or larger than 180 ms, a saccade is triggered after a short latency (around 125 ms).     

Tissue reactions of in situ formed dextran hydrogels crosslinked by stereocomplex formation after subcutaneous implantation in rats

In this study, the in vivo biocompatibility of physically crosslinked dextran hydrogels was investigated. These hydrogels were obtained by mixing aqueous solutions of dextran grafted with L-lactic acid oligomers and dextran grafted with D-lactic acid oligomers. Gelation occurs due to stereocomplex formation of the lactic acid oligomers of opposite chirality. Since gelation takes some time, in situ gel formation is possible with this system. A number of sterilization methods was evaluated for their effect on the chemical and physical properties of the hydrogel. It was shown that of the investigated options (filtration, gamma irradiation, dry-heat and autoclaving) dry-heat sterilization was the preferred method to prepare sterile gels suitable for in vivo evaluations. Two types of stereocomplex gels were prepared and implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 30 days. A mild ongoing foreign body reaction was observed characterized by infiltration of macrophages. Giant cells were only scarcely formed and the low numbers of lymphocytes showed that priming of the immune system is hardly involved. Importantly, the gels fully degraded in vivo within 15 days, which is in good agreement with the in vitro degradation behaviour of these gels. In conclusion, stereocomplexed dextran-oligolactic gels showed good biocompatibility which makes them suitable candidates for the design of controlled release devices for pharmaceutically active proteins.     

Estrogenic activity of estradiol and its metabolites in the ER-CALUX assay with human T47D breast cells

A number of metabolites of 17beta-estradiol were tested for their estrogenic activity using the ER-CA-LUX assay based on the increased expression of luciferase in exposed T47D breast cancer cells. E2beta and estrone showed similar potencies in the test, whereas E2alpha was 100 times less active. Incubation of cells with estrone (0.35 microM) resulted in the formation of E2beta, whereas the reverse reaction was observed for E2beta. The resulting equilibrium may explain the similar estrogenic potency of estrone in the test. The synthetic 17-hydroxy benzoate ester of E2beta was 3 times less active than the parent compound. The 17-hydroxy palmitate and oleate esters of E2beta, were respectively 25 and 200 times less active than the parent compound. The 2-hydroxy metabolites of E2beta and estrone showed a 5,000 to 10,000 fold lower activity. The 4-hydroxy metabolites were more potent than the 2-hydroxy metabolites, showing only a 20-200 times lower activity. The 2- and 4-methoxyesters of estrone were 700 times less active. It is concluded that the estrogenic potency of metabolites formed in cattle after treatment with E2beta, like estrone, E2alpha and especially the esters of E2beta, may be significant with respect to the potential risk of the use of estradiol for growth promotion in domestic animals in certain countries.