Zeitschriften

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Spatial expression of IKK-alpha is associated with a differential mutational landscape and survival in primary colorectal cancer

Background To understand the relationship between key non-canonical NF-κB kinase IKK-alpha(α), tumour mutational profile and survival in primary colorectal cancer.Methods Immunohistochemical expression of IKKα was assessed in a cohort of 1030 patients who had undergone surgery for colorectal cancer using immunohistochemistry. Mutational tumour profile was examined using a customised gene panel. Immunofluorescence was used to identify the cellular location of punctate IKKα expression.Results Two patterns of IKKα expression were observed; firstly, in the tumour cell cytoplasm and secondly as discrete ‘punctate’ areas in a juxtanuclear position. Although cytoplasmic expression of IKKα was not associated with survival, high ‘punctate’ IKKα expression was associated with significantly reduced cancer-specific survival on multivariate analysis. High punctate expression of IKKα was associated with mutations in KRAS and PDGFRA. Dual immunofluorescence suggested punctate IKKα expression was co-located with the Golgi apparatus.Conclusions These results suggest the spatial expression of IKKα is a potential biomarker in colorectal cancer. This is associated with a differential mutational profile highlighting possible distinct signalling roles for IKKα in the context of colorectal cancer as well as potential implications for future treatment strategies using IKKα inhibitors.Subject terms: Prognostic markers, Colorectal cancer     

Suramin induces and enhances apoptosis in a model of hyperoxia-induced oligodendrocyte injury

Recent evidence suggests oxygen as a powerful trigger for cell death in the immature white matter, leading to periventricular leukomalacia (PVL) as a cause of adverse neurological outcome in survivors of preterm birth. This oligodendrocyte (OL) death is associated with oxidative stress, upregulation of apoptotic signaling factors (i.e., Fas, caspase-3) and decreased amounts of neurotrophins. In search of neuroprotective strategies we investigated whether the polysulfonated urea derivative suramin, recently identified as a potent inhibitor of Fas signaling, affords neuroprotection in an in vitro model of hyperoxia-induced injury to immature oligodendrocytes. Immature OLs (OLN-93) were subjected to 80% hyperoxia (48 h) in the presence or absence of suramin (0, 30, 60, 120 microM). Cell death was assessed by flow cytometry (Annexin V, caspase-3 activity assay) and immunohistochemistry for activated caspase-3. Immunoblotting for the death receptor Fas, cleaved caspase-8 and the phosphorylated isoform of the serine-threonin kinase Akt (pAkt) was performed. Suramin lead to OL apoptosis and potentiated hyperoxia-induced injury in a dose-dependent manner. Immunoblotting revealed increased Fas and caspase-8 expression by suramin treatment. This effect was significantly enhanced when suramin was combined with hyperoxia. Furthermore, pAkt levels decreased following suramin exposure, indicating interference with neurotrophin-dependent growth factor signaling. These data indicate that suramin causes apoptotic cell death and aggravates hyperoxia-induced cell death in immature OLs. Its mechanism of action includes an increase of previously described hyperoxia-induced expression of pro-apoptotic factors and deprivation of growth factor dependent signaling components.     

Gaseous distension of the urinary bag during CO2 laparoscopy in the usual operative settings: Does the CO2 diffuse into the urinary bladder or is it a sign of urinary tract injury?

ObjectiveTo compare the amounts of any clinically detectable gas passage into the urinary bag in laparoscopic and open surgeries.MethodsSeventy-nine women were allocated into two surgical groups; Group 1: carbon dioxide (CO₂) laparoscopy (n=37) and Group 2: gasless laparoscopy or laparotomy (n=42). All patients had urinary catheter during the surgeries. After checking the tightness of the connection of the urinary catheter and bag operations were performed. At the end of each surgery the urine volumes were recorded. The bags were immersed into a water containing container with a volume scale. The volume rise of the container was recorded. The valve of the outlet of the bag was turned on under the water and any leakage of air bubbles was observed. The final volume of the container was recorded once again while the bag was still in the water. The two groups were compared by using the Student's t or Mann Whitney U tests.ResultsWe did not observe and hence measure any gas accumulation in the urine bags of both groups. The women's ages, total intraoperative urine volume, urine production rate and total operative times of the groups were not significantly different. The mean operative time was (82.98±62.14) min in open surgeries and (73.46±52.74) minutes in CO₂ laparoscopic surgeries. The difference between the groups was not significant (P=0.468).ConclusionsAny gas accumulation in the urine bag during CO₂ laparoscopic surgery should raise the suspicion of urinary tract injury. Urinary catheterization helps to diagnose the unnoticed bladder injuries.     

The relationship of heel pad elasticity and plantar heel pain

Loss of heel pad elasticity has been suggested as one of the possible explanations of plantar heel pain. This hypothesis is evaluated by this blinded observer prospective study, using an age and weight matched control population. Hindfoot lateral radiographs of 73 patients with plantar heel pain, 29 of whom had bilateral involvement (102 feet), and who ranged in age from 20 to 60 years, were studied and compared with 120 healthy subjects (240 feet). Heel pad thickness and heel pad compressibility index were not significantly different in patients with plantar heel pain than in healthy subjects matched for age and weight. In patients with unilateral heel pain, heel pad thickness and heel pad compressibility index on the painful side were not significantly different from the opposite painless side. The contribution of the heel pad elasticity measured as a visual compressibility index for plantar heel pain is a matter of debate.