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...     

Physiologic mechanism and preoperative prediction of new-onset dysphagia after laparoscopic Nissen fundoplication

The aim of this study was to determine whether preoperative physiologic factors can account for and be used to predict the development of postoperative dysphagia after laparoscopic Nissen fundoplication. One hundred sixty-three patients with gastroesophageal reflux disease underwent laparoscopic Nissen fundoplication with a median follow-up of 14 months (range 6 to 81 months). Preoperative dysphagia was present in 37% (60 of 163) and was relieved in all but five patients (92%). Female sex (P = 0.01) and the presence of a stricture (P = 0.02) were the only preoperative variables associated with the presence of preoperative dysphagia. Eight percent (8 of 103) of patients without preoperative dysphagia developed new-onset dysphagia, and of these 63% (5 of 8) had a normal lower esophageal sphincter (LES) (pressure >6 mm Hg; length >2 cm; abdominal length >1 cm). New-onset dysphagia was significantly more common in patients with a normal LES (22% [5 of 23] vs. 4% [3 of 80], P = 001). Patients with a normal LES had almost a sixfold increase in the risk of developing dysphagia as those with an abnormal LES (relative risk = 5.8). Only a preoperative normal LES (P = 0.02) or mean LES pressures (P = 0.04) were positively associated with the development of postoperative dysphagia. The severity of this dysphagia also showed a strong positive trend of increasing with mean preoperative LES pressures (P = 0.07). Finally, preoperative LES pressure significantly correlated with postoperative LES pressure (r = 0.48, P = 0.01) and with mean residual LES (nadir) pressure (r = 0.33, P = 0.05) offering insight into the mechanism of this dysphagia. In conclusion, preoperative LES parameters play a role in the development of dysphagia after laparoscopic Nissen fundoplication. Patients with a normal LES or high mean LES pressures are at increased risk for developing this complication and should be informed of this before laparoscopic Nissen fundoplication. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Ga., May 20–23, 2001.     

Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

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.     

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.     

Acoustic rhinometry in nasal provocation test in perennial allergic rhinitis

Acoustic rhinometry is one method to evaluate nasal geometry by an acoustic reflection technique. The aim of this study was to investigate the changes in acoustic rhinometry after nasal provocation in patients with exclusively perennial allergic rhinitis. In 19 patients, acoustic rhinometry and active anterior rhinomanometry were performed before and after nasal provocation test. There was a statistically significant nasal flow reduction measured by active anterior rhinomanometry after nasal provocation (p < 0.05) and a median symptom score of four points, both indicating a positive response to nasal provocation. On the other hand, there was no statistically significant change in the values of acoustic rhinometry after nasal provocation (p > 0.05). In patients with exclusively perennial allergic rhinitis, acoustic rhinometry does not seem to significantly change after nasal provocation. In contrast, active anterior rhinomanometry values decreased significantly after nasal provocation. The presented results indicate that acoustic rhinometry does not seem to be a diagnostic method superior to active anterior rhinomanometry in this context.     

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).