Effects of ethanol on spinal cord blood flow in the rat

This study examines the effects of low and high concentrations of ethanol on spinal cord blood flow (SCBF) in the rat. SCBF was measured in the following blood pressure ranges: (a) <60 mm Hg, (b) 60-90 mm Hg, (c) 90-120 mm Hg, (d) 120-150 mm Hg, and (e) >150 mm Hg. Rats were anesthetized with 1.4% isoflurane in air and randomly assigned to the following treatment groups: group 1 (n = 12), intraperitoneal (i.p.) saline injection; group 2 (n = 10), 1 g/kg of ethanol i.p.; and group 3 (n = 14), 4 g/kg of ethanol i.p. Blood pressure was increased by intravenous phenylephrine infusion or lowered by a combination of intravenous trimethaphan and blood withdrawal. The SCBF was measured in cervical, thoracic, and lumbar segments using radioactive microspheres. The plasma ethanol concentration was 0 mg/ml for group 1, 0.64 +/- 0.06 mg/ml (mean +/- SEM) in group 2, and 4.18 +/- 0.11 mg/ml in group 3. In control rats, the cervical SCBF was higher than the thoracic or lumbar SCBF, evaluated over the entire blood pressure range (analysis of variance, p <0.05). This difference in regional SCBF was abolished by ethanol. Ethanol produced a significant decrease in cervical and lumbar SCBF (p <0.05) but not thoracic SCBF (p = 0.07). This decrease in SCBF was most pronounced at high blood pressures. These results suggest that ethanol produces vasoconstriction in the spinal cord that is countered by autoregulatory vasodilation at low blood pressures.     

Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells.

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) (Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of non-irradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h (before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose- and time-dependent manner with cancer cells having a stronger impact at low doses.     

Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies.

PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.     

Neuroprotective and symptomatological action of memantine relevant for alzheimer’s disease — a unified glutamatergic hypothesis on the mechanism of action

The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer's disease is finding increasingly more acceptance in the scientific community. Central to this hypothesis is the assumption that in particular glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner. Such continuous mild activation leads under chronic conditions to neuronal damage. Moreover, one should consider that impairment of plasticity (learning) may result not only from neuronal damage per se but also from continuous activation of NMDA receptors. To investigate this possibility we tested whether overactivation of NMDA receptors using either non-toxic doses/concentrations of a direct NMDA agonist or through an indirect approach--decrease in magnesium concentration--produces deficits in plasticity. In fact NMDA both in vivo (passive avoidance test) and in vitro (LTP in CA1 region) impaired learning and synaptic plasticity. Under these conditions memantine which is an uncompetitive NMDA receptor antagonist with features of "improved magnesium" (voltage dependence, affinity) attenuated the deficit. The more direct proof that memantine can act as a surrogate for magnesium was obtained in LTP experiments under low magnesium conditions. In this case as well, impaired LTP was restored in the presence of therapeutically relevant concentrations of memantine (1 microM). In vivo, doses leading to similar brain/serum levels produce neuroprotection in animal models relevant for neurodegeneration in Alzheimer's disease such as neurotoxicity produced by inflammation in the NBM or beta-amyloid injection to the hippocampus. Hence, we postulate that if in Alzheimer's disease overactivation of NMDA receptors occurs indeed, memantine would be expected to improve both symptoms (cognition) and slow down disease progression because it takes over the physiological function of magnesium.     

Radionuclide imaging in patients with amputations of the lower leg: typical imaging patterns in five cases

Amputation of the lower leg is not uncommon in elderly patients with chronic infections or vascular problems of the leg and foot, and most often it is performed below the knee or on the distal part of the lower leg (i.e., Syme's amputation). After operation, healing disorders with or without infection can occur, and usually structural imaging methods are performed for diagnosis. Radionuclide imaging using a combination of bone scans and infection scintigraphy can help to identify bone and soft tissue infection. Interpreting radionuclide scans is difficult, because imaging findings after amputation may depend not only on the level of resection and the disease investigated but also on the time that has elapsed since surgery. Typical imaging patterns of bone or infection scintigraphy of five patients are described     

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19–55) y, and mean body mass index was 22.43 (17.3–30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p?=?0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r?=?0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.     

Influenza and pneumococcal vaccination in patients with rheumatoid arthritis in comparison with age- and sex-matched controls: results of a claims data analysis

The aim of this study was to assess the vaccination status for influenza and pneumonia and the prevalence of hospitalised pneumonia in rheumatoid arthritis (RA) patients and population controls in Germany. Members of a large statutory health insurance fund in Germany who were continuously insured between 2009 and 2013 and had a diagnosis of RA in 2013 were age and sex matched 1:5 to members without RA. Pneumococcal and influenza vaccinations were evaluated with regard to age, sex and region of residence. Logistic regression models were used to determine predictors for influenza vaccination in RA patients. Prevalences of pneumonia that required hospitalisation were compared to regional vaccination rates. The data of 111,482 RA patients and 557,410 matched controls were available for analysis. Compared to controls, RA patients were vaccinated more frequently against influenza (40.8 vs. 32.2 %) and pneumonia (15.0 vs. 10.0 %). Vaccination rates increased with older age and differed between the federal states (highest in East Germany, lowest in South Germany). The region of residence, comorbidities, rheumatologic care and biologic treatment was associated with a higher probability of an influenza vaccination. Prevalences of pneumonia that required hospitalisation were 2–3 times higher in patients compared to controls and tended to be higher in regions with low vaccination rates. The increased pneumonia prevalence in RA patients confirms their status as a risk group. RA patients are vaccinated more frequently than controls, but vaccination rates are still low. The lower pneumonia prevalence in East Germany indicates that vaccination may help to reduce pneumonia in RA.