Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Immediate-early gene expression in cerebral cortex following exposure to chronic-intermittent hypoxia

Chronic-intermittent hypoxia (CIH) was postulated to evoke c-fos expression in cortical regions that modulate sympathetic discharge. Animals exposed to CIH for 30 days exhibited c-fos labeling in medial prefrontal, cingulate, retrosplenial, and insular cortices. Our findings strongly suggest activation of cortical circuits that adaptively regulate sympathetic and cardiovascular activities.     

Proxy decision in health questions and advance designations by patients. A practice-oriented review of the legal and ethical problems in treating the incompetent patient

Except in emergencies, the medical treatment of incompetent patients also has to be based upon an informed consent between the physician and a legitimate legal representative (durable power of attorney). Consequently, the German 'Betreuungsrecht' advices persons to designate in advance such a proxy or surrogate. However, an additional court-decision is demanded, if a medical measure poses significant risks for the future health or the life of the incompetent patient. On the base of the available epidemiologic data we illustrate that neither our medical nor our legal system could realistically cope with the practical consequences of this legislation: The vast majority of our present decisions in such cases is not covered by a legally valid informed consent, which implies possible forensic consequences. This article provides relevant clinical and legal advice on how to protect the legitimate interests of all concerned within the present framework, which should urgently be revised.     

A noninvasive objective measure of sunscreen use and reapplication.

OBJECTIVES: To study whether a noninvasive swabbing technique can detect sunscreen use for up to 6 hours, and whether the technique can detect reapplication of sunscreen. METHODS: Thirty volunteer office workers were randomly assigned to have one of a variety of sunscreens applied using recommended application techniques, and half were randomly assigned to have sunscreen reapplied after 3 hours. Alcohol-based swabs were used to obtain a sample from participants' arm at 20 minutes, and hourly from 1 to 6 hours post-application. Absorption readings were analyzed using an UV-visible spectrophotometer. RESULTS: The swabbing technique was consistently able to distinguish the sunscreen from control swabs for up to 6 hours. The absorption readings between 20 minutes and 6 hours were significantly higher than control swabs. There were no differences between the group that had sunscreen reapplied and the group that did not. CONCLUSION: The sunscreen swabbing technique is an effective noninvasive method for detecting a variety of sunscreen products in adults over a 6-hour period. No differences in absorption readings were found with sunscreen reapplication. This procedure will be a useful adjunct to other objective measures of sun protection and UV radiation exposure, resulting in a more accurate picture of the sun protection habits of individuals.