Morphologische und funktionelle Ver?nderungen der Nasenschleimhaut nach nCPAP-Therapie

Hintergrund und Fragestellung. Der Therapieerfolg einer nCPAP-Therapie (“nasal continuous positive airway pressure”) ist einerseits abh?ngig von der Linderung der Beschwerden und andererseits von der Langzeitakzeptanz und der hiermit verbundenen Vermeidung von Komplikationen. Nasale Beschwerden sind die h?ufigsten Nebenwirkungen und neben den Maskenproblemen die wichtigste Ursache, weshalb eine nCPAP-Therapie frühzeitig unterbrochen wird.     

Potentiation of interleukin 1 alpha mediated antitumor effects by ketoconazole

In the present studies, the regulatory role of adrenal hormones on the antitumor activity of recombinant human interleukin 1 alpha (IL-1 alpha) was investigated. Ketoconazole, a potent but transient inhibitor of adrenal steroid hormone biosynthesis, inhibited IL-1 alpha induced increases in plasma corticosterone. In s.c. RIF-1 tumors (C3H/HeJ mice) ketoconazole potentiated IL-1 alpha induced hemorrhagic necrosis (59Fe labeled RBC uptake) and prolonged intervals of low tumor perfusion (86Rb+ uptake) and attendant depletion of tumor high energy phosphate reserves as determined by in vivo 31P nuclear magnetic resonance spectroscopy. In normal muscle and skin the ketoconazole-IL-1 alpha combination had no effect on RBC content and little or no effect on tissue perfusion. Ketoconazole potentiation of IL-1 alpha induced tumor pathophysiologies was accompanied by time and ketoconazole dose dependent potentiation of RIF-1 tumor clonogenic cell killing. Although ketoconazole at 40 mg/kg and IL-1 alpha at 25 micrograms/kg alone each produced approximately 50% clonogenic cell kill, a combined treatment (IL-1 alpha 1 h after ketoconazole) resulted in surviving fractions of approximately 1.5%. In vitro, ketoconazole and IL-1 alpha induced only additive clonogenic cell kill in primary RIF-1 explant cultures. The effect of elevated plasma corticosterone levels, induced by ketamine-acepromazine anesthesia, on IL-1 alpha responsiveness was also studied in the RIF-1 tumor model. In C3H/HeJ mice, anesthesia increased plasma corticosterone levels within 30 min, abrogated the IL-1 alpha effect on tumor perfusion, and prevented depletion of tumor high energy phosphate metabolite reserves. Our results are consistent with the hypothesis that IL-1 alpha mediated adrenal hormone responses exert a profound negative feedback on IL-1 alpha antitumor activities. Our data also indicate that adrenal steroid hormone biosynthetic pathways could provide a focus for modulation strategies to increase the efficacy of cytokine based therapeutic interventions.     

Bronchodilatory responses to formoterol, ipratropium, and their combination in patients with stable COPD

We studied 27 patients with stable chronic obstuctive pulmonary disease (COPD) in a randomised, single-blind, within-patient, placebo-controlled clinical study. Each patient was assigned on six separate days to receive one of the following drug regimens in random order: A. 40 micrograms ipratropium bromide (Atrovent MDI, 20 micrograms/puff) plus 2 puffs placebo; B. 12 micrograms formoterol fumarate (Foradil MDI, 12 micrograms/puff) plus 3 puffs placebo; C. 80 micrograms ipratropium; D. 24 micrograms formoterol plus 2 puffs placebo; E. 12 micrograms formoterol plus 40 micrograms ipratropium plus 1 puff placebo; F. 4 puffs placebo. On each study day, spirometric indices and vital signs were measured at 5, 10, 15 and 60 minutes, and hourly thereafter up to and including 12 hours after study drug administration. Mean peak FEV1 change (primary endpoint) was maximum with the administration of the combination of ipratropium and formoterol (335.2 ml, SE 24.6), and it differed significantly from the observed peak changes following single administration of the two tested doses of ipratropium (p < 0.05 and p < 0.05 respectively). Safety and tolerability were satisfactory throughout the study.     

Ureteral Obstruction: Is the Full Metallic Double-Pigtail Stent the Way to Go?

Background

The Resonance metallic ureteral stent (Cook Medical, Bloomington, Indiana, USA) has been introduced for the management of extrinsic-etiology ureteral obstruction for time periods up to 12 mo.

Objective

The current study aims to determine short- and medium-term effectiveness of the Resonance stent in malignant and benign ureteral obstruction.

Design, setting, and participants

In total, 50 patients with extrinsic malignant obstruction (n = 25), benign ureteral obstruction (n = 18), and previously obstructed mesh metal stents (n = 7) were prospectively evaluated.

Intervention

All patients were treated by Resonance stent insertion. Twenty stents were inserted in antegrade fashion, and the remaining stents were inserted in a retrograde approach. No patient dropped out of the study. The follow-up evaluation included biochemical and imaging modalities.

Measurements

We evaluated the technical success rate, stricture patency rate, complications, and the presence and type of encrustation.

Results and limitations

The technical success rate of transversal and stenting of the strictures was 100%. In 19 patients, balloon dilatation was performed prior to stenting. The mean follow-up period was 8.5 mo. The stricture patency rate in patients with extrinsic malignant ureteral obstruction was 100% and in patients with benign ureteral obstruction 44%. Failure of Resonance stents in all cases of obstructed metal stents was observed shortly after the procedure (2–12 d). In nine cases, stent exchange was demanding. Encrustation was present in 12 out of 54 stents.

Conclusions

The Resonance stent provides safe and sufficient management of malignant extrinsic ureteral obstruction. Resonance stent use in benign disease needs further evaluation, considering the untoward results of the present study.     

Does Re-operation have an Effect on Outcome Following Heart Transplantation?

OBJECTIVE: Previous cardiac operation has traditionally been considered as a potential risk factor for patients undergoing heart transplantation. This study aimed to evaluate the outcome of patients undergoing heart transplantation as a second cardiac procedure and compare it with primary heart transplantation, using meta-analytical methodology. METHODS: A literature search was undertaken to identify relevant comparative studies. Outcomes of interest were classified into four categories: (a) intra-operative times; (b) post-operative outcomes; (c) resources; (d) actuarial outcomes. RESULTS: Seven studies matched the selection criteria, reporting on 1004 patients. Six hundred and twenty-three had transplantation as primary operation and 381 as re-operation. The 1-year, 2-year, and 5-year mortality were similar for the two groups (HR=0.85, p=0.54; HR=0.97, p=0.88; and HR=1.04, p=0.92, respectively). Total operative, cold-ischaemic, by-pass, and cross-clamp times were significantly longer for the re-operation group by 59.44 (p<0.001), 14.62 (p=0.05), 25.24 (p<0.001), and 7.93 (p<0.001)min, respectively. Both ICU and hospital stay were longer for the re-operation group but only the former was statistically significant (WMD=1.37; p=0.02). Post-operative complications were similar, except re-exploration rate and blood transfusion requirement, which were higher in the re-operation group (OR=3.51; p<0.001 and WMD=2.21; p<0.001, respectively). CONCLUSIONS: Heart transplantation following previous cardiac operation is technically demanding requiring longer operative times compared to primary heart transplantation. It does not, however, add a significant risk to the survival of the patient, and associated morbidity is not significantly compromised.     

An early transient 40 Hz activity discriminates a following pro-saccade from a no-move and anti-saccade choice

We studied the oscillatory activity of the scalp-recorded EEG in healthy humans performing a task that required a particular eye-movement response choice according to the shape of a visual target. We observed a significant stimulus-aligned activity at the 40 Hz frequency band 100 ms after the appearance of the target only when that target was the end point for the subsequent eye movement (pro-saccade). This activity was most prominent over the central-parietal area of the right hemisphere. When the target indicated a movement to the opposite direction (anti-saccade) or indicated that no movement was required (no-move), this 40 Hz activity was nearly absent. This difference in activity between the pro-saccade and the other two tasks was evident in the single subject ERPs for four of the six subjects studied. In contrast, the movement-aligned 40 Hz activity for the pro-saccade and anti-saccade was almost identical. We speculate that this early stimulus-aligned 40 Hz activity might reflect a fast transformation of a visual stimulus to a motor response (eye movement) that can be performed for the pro-saccade task where stimulus-response compatibility is strong compared to the anti-saccade and no-move tasks. The movement-aligned 40 Hz activity might be related to the motor response preparation per se. We conclude that this task specific transient oscillatory activity could be used as a probe in the study of the temporal dynamics of visuomotor transformations.