Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Brain tissue microarrays in dementia research: White matter microvascular pathology in Alzheimer's disease

Tissue microarrays (TMA) consist of up to 1000 cylindrical tissue cores from different donor paraffin blocks relocated into one recipient block, allowing for efficient histopathological studies by fluorescence in situ hybridization, RNA in situ hybridization or immunohistochemistry. On the background of the increasing interest of the TMA technique in cancer research and the suggestion of its application also in studies of non‐neoplastic intracranial disorders, the technique was applied to pathologic white matter in AD brains. Eight cases with AD and concomitant white matter pathology were neuropathologically diagnosed on whole brain coronal slides. The TMA technique was used to grade severity of white matter pathology and to quantify small vessels with traditional staining and immunohistochemical markers. These measurements were compared with the whole brain neuropathological assessment. The technique produced good results with preserved tissue structures as confirmed by the whole brain evaluation. Severity of white matter pathology evaluated on the TMA cores correlated negatively with small vessel quantities, and statistically significant differences in vessel quantities paralleled different grades of white matter pathology. It is concluded that the TMA technique could be further utilized in studies of dementing disorders, and may have its advantages in large, clinically well‐characterized materials (e.g. in quantitative mapping of white matter changes).     

The effect of major railway accidents on the psychological health of train drivers—I. Acute psychological responses to accident

The acute psychological reactions of 101 train drivers to on-the-track accidents were studied by means of clinical interviews and questionnaires (Impact of Event Scale, GHQ-20 and a questionnaire addressing stress symptoms, pre-accident expectancies and worries). More than half of the train drivers reported moderate to high intrusive distress (mean 11.3) within hours to days after the accident but only 1/3 reported symptoms of acute psychophysiological arousal. Intrusive symptoms related to visual impressions were most frequently reported. Avoidance was less prevalent (mean 8.8).

Clinical interviews, relationship between pre-accident worries and severity of the acute responses and positive correlation between GHQ-scores relating to the fortnight preceding the accident and IES-intrusion scores, suggest that premorbid variables may influence the stress response. Involvement in more than two previous accidents invoked a feeling of vulnerability and produced stronger acute responses. Post-accident experiences involving various personal contacts did not correlate with the stress responses in this study and only a few drivers experienced such events in a negative way. Denial of the possibility of being involved in accidents was not associated with increased risk of strong acute responses, indicating that denial does not predict poor outcome in healthy persons exposed to situations where possibility of avoiding the event is outside the control of the person.     

Thorakale Strahlentherapie

Zusammenfassung Beim kleinzelligen Lungenkarzinom muss die Dosisintensität der zytotoxischen Behandlungsmodalitäten als wichtige therapeutische Größe angesehen werden. Dies gilt sowohl für die Chemo- als auch die Strahlentherapie in ihrer Kobination. Die Mehrheit der verfügbaren Evidenz deutet an, dass der frühe Einsatz der thorakalen Strahlentherapie, simultan mit einer platinbasierten Zweitgenerationschemotherapie, einen moderaten therapeutischen Vorteil bei Patienten im UICC-Stadium I–III bietet.     

The meaning of work after acquired brain injury.

PURPOSE: Research in the field of brain injury rehabilitation has tended to regard return to work as a measure of outcome. Researchers have not paid particular attention to the experiences of people living with a brain injury. The aim of the phenomenological study reported here was to identify and describe what characterizes the meaning of work to those with acquired brain injury. METHODS: Ten participants of working age were interviewed about the meaning of work 1-5 years after being inflicted with a brain injury. Data were analyzed and interpreted using the Empirical Phenomenological Psychological method. RESULTS: The findings revealed a meaning structure consisting of four main characteristics. Work was no longer experienced as the primary event in life and the social dimension had become more important. The perceived competence and work identity were threatened after the injury. A common theme across all interviews was the struggle to return to a state of normality, and working was considered to be evidence of success. CONCLUSION: The findings described the altered meaning of work 1-5 years after brain injury. This knowledge should lead to an increased understanding among occupational therapists engaged in work rehabilitation after brain injury and can serve as a basis for individualized intervention strategies.