Überregionale Public-Health-Akteure in Deutschland – eine Bestandsaufnahme und Kategorisierung

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Akteure der öffentlichen Gesundheit (Public Health) tragen wesentlich zu Gesundheitsschutz, -förderung und...     

Cytokeratin expression in a congenital multipotential primitive neuroectodermal tumor

A case of an uncommon congenital primitive neuroectodermal cerebellar tumor (PNET) in a 5-month-old child is reported. After subtotal surgical resection, the residual tumor did not respond to radiation and chemotherapy. Histologically, the tumor was composed of small, round, undifferentiated cells and several other patterns like astrocytomatous, oligodendrogliomatous, and ependymomatous structures. Immunostaining was positive for most of the cells for vimentin and S 100, fewer were positive for glial fibrillary acid protein (GFAP) and neuron-specific enolase, and only a few for synaptophysin. Surprisingly, the tumor showed strong expression of several monoclonal cytokeratins (CK) with different molecular weights, together with epithelial membrane antigen. Furthermore, we found a coexpression of the tumor cells for CK and vimentin, while CK-GFAP and CK-S 100 were negative. Ultrastructurally, intracyto-plasmic intermediate filaments could be observed corresponding to immunohistochemical CK expression. The very strong CK and vimentin expression in this case was interpreted as a sign of the embryonic nature of the tumor.     

Isolation of a rat S100 alpha cDNA and distribution of its mRNA in rat tissues.

In order to clarify the reported discrepancies in S100 alpha protein and mRNA distribution in rat tissues, a rat S100 alpha cDNA has been isolated and this species homologous probe along with a rat S100 beta cDNA probe has been used to examine S100 mRNA expression in rat tissues. Although the rat S100 alpha cDNA was missing approximately 30 nucleotides of coding sequence, only 4 conservative changes in amino acid sequence were observed when the deduced amino acid sequence was compared to the bovine S100 alpha amino acid sequence. Thus, S100 alpha proteins, like S100 beta proteins, are highly conserved among species. All nineteen of the tissues examined (including cerebrum and cerebellum) contained S100 alpha mRNA. In addition, S100 beta mRNA was detected in thirteen of the nineteen tissues examined. These results are in agreement with previous protein distribution studies and further demonstrate that S100 proteins are not brain-specific and are expressed in a large number of tissues. Although S100 alpha and S100 beta mRNAs were detected in rat tissues which had previously been reported to contain S100 alpha and S100 beta protein, a direct correlation between the protein and mRNA levels were not observed, suggesting that different mechanisms regulate S100 expression in various tissues. S100 alpha exhibited a single similar size mRNA species (0.5 Kb) in all tissues examined, as did S100 beta (1.5 Kb), suggesting that the individual S100 proteins are expressed as single mRNA and protein products in rat tissues.     

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.     

Inspired Oxygen Fraction of 0.8 Does Not Attenuate Postoperative Nausea and Vomiting after Strabismus Surgery

Background: Postoperative nausea and vomiting (PONV) is a distressing problem after strabismus surgery. An inspired oxygen fraction has been reported to decrease PONV in patients after colon resection and to be more effective than ondansetron after gynecologic laparoscopy. Therefore, in a randomized, prospective, placebo-controlled study, the authors tested whether an inspired oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery and whether oxygen is more effective than ondansetron.

Methods: With approval of the authors' institutional review board, 210 patients were randomly assigned to receive one of three treatments: (1) 30% inspired oxygen in air plus intravenous administration of saline, (2) 80% inspired oxygen in air plus intravenous administration of saline, or (3) 30% inspired oxygen in air plus 75 [mu]g/kg ondansetron intravenously during induction. General anesthesia was standardized and included etomidate, alfentanil, and mivacurium for induction and sevoflurane for maintenance. PONV was evaluated 6 and 24 h postoperatively by an investigator unaware of treatment assignment.

Results: Overall postoperative incidence of nausea and vomiting was 41% for inspired oxygen fraction of 0.3 plus placebo, 38% for inspired oxygen fraction of 0.8 plus placebo, and 28% for inspired oxygen fraction of 0.3 plus ondansetron, respectively (P = 0.279). Therefore, there was no statistically significant difference of PONV incidence among groups.     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.     

Exogenous Modulation of TGF-β1 Influences TGF-βR-III-Associated Vascularization during Wound Healing in Irradiated Tissue

BACKGROUND AND PURPOSE: Following preoperative radiotherapy prior to ablative surgery of squamous epithelial cell carcinomas of the head and neck region, wound-healing disorders occur. Previous experimental studies showed altered expression of transforming growth factor-(TGF-)beta isoforms following surgery in irradiated graft beds. Altered levels of TGF-beta(1) are reported to promote fibrosis and to suppress vascularization during wound healing, whereas expression of TGF-beta receptor-III (TGF-betaR-III) is associated with vascularization. The aim of the study was to analyze the influence of anti-TGF-beta(1) treatment on TGF-betaR-III-associated vascularization in the transition area between irradiated graft bed and graft. MATERIAL AND METHODS: Wistar rats (male, weight 300-500 g) underwent preoperative irradiation of the head and neck region with 40 Gy (four fractions of 10 Gy each; n = 16 animals). A free myocutaneous gracilis flap taken from the groin was then transplanted to the neck in all rats. The time interval between operation and transplantation was 4 weeks. Eight animals received 1 micro g anti-TGF-beta(1) into the graft bed by intradermal injection on days 1-7 after surgery. On days 3, 7, 14, 28, 56, and 120, skin samples were taken from the transition area between transplant and graft bed and from the graft bed itself. Immunohistochemistry was performed using the ABC-POX method to analyze the TGF-betaR-III and E-selectin expression. Histomorphometry was performed to analyze the percentage and the area of positively stained vessels. RESULTS: A significantly higher expression of TGF-betaR-III was seen in the irradiated and anti-TGF-beta(1)-treated graft bed in comparison to the group receiving preoperative irradiation followed by transplantation alone. The percentage of TGF-betaR-III positively staining capillaries from the total amount of capillaries in the anti-TGF-beta(1)-treated graft bed was higher than in the group irradiated only. The total area of capillaries was also higher in the TGF-beta(1)-treated group. CONCLUSION: Neutralizing of TGF-beta(1) activity in irradiated tissue undergoing surgery leads to a higher expression of TGF-betaR-III and increased vascularization. TGF-betaR-III seems to be associated with newly formed blood vessels during neovascularization in wound healing.     

Multicenter retrospective development and validation of a clinical prediction rule for nosocomial invasive candidiasis in the intensive care setting

The study presented here was performed in order to create a rule that identifies subjects at high risk for invasive candidiasis in the intensive care setting. Retrospective review and statistical modelling were carried out on 2,890 patients who stayed at least 4 days in nine hospitals in the USA and Brazil; the overall incidence of invasive candidiasis in this group was 3% (88 cases). The best performing rule was as follows: Any systemic antibiotic (days 1–3) OR presence of a central venous catheter (days 1–3) AND at least TWO of the following—total parenteral nutrition (days 1–3), any dialysis (days 1–3), any major surgery (days −7–0), pancreatitis (days −7–0), any use of steroids (days −7–3), or use of other immunosuppressive agents (days −7–0). The rate of invasive candidiasis among patients meeting the rule was 9.9%, capturing 34% of cases in the units, with the following performance: relative risk 4.36, sensitivity 0.34, specificity 0.90, positive predictive value 0.01, and negative predictive value 0.97. The rule may identify patients at high risk of invasive candidiasis. Results of this project were partially presented at Focus on Fungal Infections 14, New Orleans, LA, USA, 2004. Abstract no. 51.