Differential synthesis and binding of hyaluronan by human breast cancer cell lines

In the present study we investigated a panel of human breast cancer cell lines which were sensitive or resistant to the cytotoxic drug doxorubicin, for their abilities to synthesize and bind hyaluronan. We found that MDA-231 and HS-578T cells which express very low amounts of estrogen and progesterone receptors, both synthesized hyaluronan and expressed hyaluronan binding sites on the cell surface as did their doxorubicin-adapted counterparts MDA-231 Dox and HS-578T Dox. The binding was highly specific with a K-d of 0.48x10(-9) M. Most of the hyaluronan binding activity was blocked by mAbs against Hermes-l antigen indicating that the adhesion molecule CD44 is responsible for hyaluronan binding. Only 0.5% of the total amount of labeled hyaluronan added to the cultures was degraded during a period of 16 h. The hormone positive receptor cell lines, MCF-5, Zr-5-1 and Zr-5-1 Dox synthesized only minute amounts of hyaluronan and did not bind hyaluronan or express CD44 receptors. Expression of CD44-related hyaluronan receptors and synthesized hyaluronan may endow hormone receptor negative cells with a highly hydrated environment that facilitates cell motility and invasiveness. The lack of CD44 and thereby the lack of ability to bind hyaluronan in the extracellular matrix may contribute to the non-invasive behavior of hormone positive cell lines.     

Cerebral disseminated coagulation

Summary The distribution of cytarabine in the ventricular CSF was studied after lumbar intrathecal administration. In the ventricular fluid peak concentrations up to 1.5×10^–4 M (37 g/ml) were achieved 4–8 h after lumbar injection of cytarabine of 45 mg/m². The concentration of cytarabine decreased slowly with a half-time of 2.16 h thus providing therapeutic concentrations in the cerebral ventricles for more than 24 h.

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Zusammenfassung Die Verteilung von Cytosinarabinosid nach lumbaler intrathekaler Injektion im ventrikulären Liquor cerebrospinalis wurde untersucht.Nach lumbaler intrathekaler Injektion von 45 mg Cytosinarabinosid (Alexan®) pro m² Körperoberfläche wurde im ventrikulären Liquor eine Höchstkonzentration von 1,5×10^–4 M (37 g/ml) 4–8 h nach Applikation erreicht. Die Konzentration von Cytosinarabinosid im ventrikulären Liquor fiel langsam mit einer Halbwertszeit von 2,16 h ab. Bei lumbaler Applikation wurden bei dieser Untersuchung therapeutische Konzentrationen von Cytosinarabinosid in den cerebralen Ventrikeln für mehr als 24 h erreicht.

     

Acute effects of interferon beta-1a on plasma cytokine levels in patients with MS

The acute effects of a i.m. injection of interferon beta-1a on the secretion of the cytokines interleukin-6, tumor necrosis factor-alpha, soluble tumor necrosis factor receptor I, and interleukin-1 receptor antagonist and its relation to peripheral concentrations of adrenocorticotropic hormone (ACTH) and cortisol in patients with MS were investigated, as well as the influence of cotreatment with indomethacin on these parameters. After interferon beta injection we found an acute rise in plasma cytokine levels and an increase in plasma hormone concentrations, both of which were modulated by indomethacin comedication.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

An arachnoid cyst presenting as an intramedullary tumour

A case of thoracic intradural extramedullary arachnoid cyst is presented in which an intramedullary low grade glioma was suspected preoperatively. The cyst was widely fenestrated and postoperatively, the patient experienced considerable improvement in her symptoms. As postoperative MRI studies also showed resolution of the intramedullary changes we regard the intramedullary changes as a result of the cyst, without the existence of primary medullary pathology. To our knowledge an arachnoid cyst, to date, has not been described as the cause of syringomyelia. As radiological findings can be misleading, extramedullary pathology, located more cranially, should be ruled out when treating cystic medullary changes.