Domestic allergens and endotoxin in three hospitals offering in-patient rehabilitation for allergic diseases in the alpine mountain climate of Bavaria - The AURA study.

Endotoxins and allergens represent the major relevant contents of the atmospheric bioaerosol with regard to the triggering and exacerbation of allergic diseases. In this study, mattress concentrations of endotoxin and indoor allergens were measured in three hospitals in the alpine climate of Bavaria and in adjacent homes. Dust was collected from each of 10 mattresses according to a standardized protocol, and endotoxin was analyzed with the Limulus Amebocyte Lysate (LAL) test, indoor allergens Der p 1, Der f 1 and Fel d 1 were analyzed by ELISAs. The concentration of endotoxin in the mattresses did not differ significantly between different cities. The percentiles of endotoxin were significantly higher in hospitals than in homes. The concentrations of mite allergens (Der p 1 and Der f 1) in the dust were significantly lower in all hospitals than in homes. There was no significant difference of mite allergens between different time points. The concentrations of Fel d 1 were significantly higher in the autumn than in the summer (median: 1376 vs. 478ng/g). No significant differences of Fel d 1 were found between hospitals and homes or between different hospitals. As Fel d 1 concentrations reached levels at which cat allergic patients can experience symptoms, efforts had to be made to reduce the concentrations of Fel d 1 especially in hospitals. In contrast, mite allergens were low in hospitals, which can be clinically beneficial for patients with mite allergies.

Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin.

Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators-Slug and E12/E47-in primary human gastric carcinomas and to compare this with the expression of E-cadherin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p<0.0001). Twenty-one cases (36%) showed E12/E47 up-regulation that was not significantly associated with E-cadherin down-regulation (p=0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p=0.0029) and with advanced pTNM stages (p=0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p=0.0014) and Snail in diffuse (p=0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators.

MRI lesions after invasive therapy of carotid artery stenosis: a risk-modeling analysis.

BACKGROUND: Diffusion-weighted imaging (DWI) abnormalities can frequently be detected after carotid endarterectomy (CEA) and carotid angioplasty with stent placement (CAS) of the carotid arteries. We looked for possible predictors for the development of DWI lesions during the intervention. METHODS: We investigated 41 patients who underwent CAS without protection devices and 93 patients who underwent CEA. DWI studies were performed 1 day before and after the intervention. RESULTS: Ischemic complications consisted of two strokes (2.2%) in the CEA group and one stroke (2.4%) in the CAS group. DWI lesions were detected in 28.0% of all patients after intervention. Using a multivariate regression analysis, diabetes mellitus (DM), hyperlipidemia, symptomatic stenosis, age and CAS were found to be significant predictors for the occurrence of DWI lesions. CONCLUSIONS: DWI is an objective and highly sensitive method for monitoring interventions of the carotid arteries. Our results point to an increased risk of patients with diabetes and hyperlipidemia to develop DWI lesions during invasive therapy of the ICA.

[Is there an association between the sleep apnea syndrome and the circadian peak of myocardial infarction in the morning hours?]. / Besteht ein Zusammenhang zwischen dem Schlafapnoesyndrom und der zirkadianen Häufung von Myokardinfarkten in den Morgenstunden?

OBJECTIVE: To determine whether there is a relationship between the circadian rhythm of acute myocardial infarction (AMI) in the morning hours and the sleep apnea syndrome (SAS). PATIENTS AND METHODS: 203 patients who had sustained an AMI were examined 7-14 days later for sleep-associated breathing disorders using a 5-channel recording system. The diagnostic criterion for SAS was > 10 episodes of apnea and hypopnea per hour (AHI >10). 76 % of all patients were male, mean age 62 years. RESULTS: SAS was diagnosed in 91 of the 203 patients (44.8 %). Compared to the 112 patients without SAS there were significantly more AMI in the morning hours (6:00 am to 12:00 am) in the SAS-group (49.5 %) than in the non-SAS-group (21.4 %). The two groups differed with regard to the symptoms of day-time sleepiness (29.7 % vs 17.0 %), age (mean 64.6 years vs 60.2 years), gender (83.5 % vs 69.9 % male) and smoking (33.0 % vs 51.8 %). There were no significant differences in Body mass index, hypertension, hyperlipoproteinemia, diabetes mellitus, family history, history of cardiovascular disease and taking of sedatives. CONCLUSION: The strong association between SAS and morning onset of AMI found in this study could be the result of a sympathetic stress reaction to the breathing disorder.

Effectiveness of 4 pulpotomy techniques--randomized controlled trial.

Pulpotomy is the accepted therapy for the management of cariously exposed pulps in symptom-free primary molars; however, evidence is lacking about the most appropriate technique. The aim of this study was to compare the relative effectiveness of the Er:YAG laser, calcium hydroxide, and ferric sulfate techniques with that of dilute formocresol in retaining such molars symptom-free. Two hundred primary molars in 107 healthy children were included and randomly allocated to one of the techniques. The treated teeth were blindly re-evaluated after 6, 12, 18, and 24 months. Descriptive data analysis and logistic regression analysis, accounting for each patient's effect by a generalized estimating equation (GEE), were used. After 24 months, the following total and clinical success rates were determined (%): formocresol 85 (96), laser 78 (93), calcium hydroxide 53 (87), and ferric sulfate 86 (100). Only calcium hydroxide performed significantly worse than formocresol (p = 0.001, odds ratio = 5.6, 95% confidence interval 2.0-15.5). In conclusion, calcium hydroxide is less appropriate for pulpotomies than is formocresol.

Cardiac magnetic resonance imaging: long term reproducibility of the late enhancement signal in patients with chronic coronary artery disease.

OBJECTIVE: To determine long term reproducibility of the late enhancement (LE) signal in contrast enhanced magnetic resonance imaging (MRI) and potential changes of the signal after revascularisation. METHODS: 33 patients (29 men, mean (SD) 61 (11) years) with coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30 (7)%) underwent two contrast enhanced MRI procedures within 9 (3) months. Fifteen patients (group A: 14 men, 59 (12) years) had no interventions between the two studies. Eighteen patients underwent revascularisation after MRI 1 (group B: 15 men, 62 (9) years). Changes in the LE signal between the first and second MRIs were investigated in both groups as well as intraobserver and interobserver variabilities for delineation of the signal. RESULTS: The LE signal was highly reproducible in groups A and B for segmental analysis (concordance 86% v 82%, respectively; kappa = 0.70 v 0.67) and summed scores (group A: r = 0.97, p < 0.001; group B: r = 0.93, p < 0.001). The LE signal was quantified as 27 (27) cm3 in group A versus 30 (16) cm3 in group B in the first MRI and 26 (25) cm3 versus 30 (15) cm3, respectively, for the second MRI (both not significant). Moreover, low intraobserver and interobserver variabilities were observed in segmental analysis (kappa = 0.86 and 0.74, respectively, for group A, and kappa = 0.87 and 0.82, respectively, for group B). CONCLUSION: In patients with chronic CAD, the LE signal in contrast enhanced MRI is very stable over an extended time period. These results further characterise contrast enhanced MRI as a useful tool for myocardial viability assessment. Low intraobserver and interobserver variabilities promise robustness of the method for clinical application.

[MS registry in Germany--design and first results of the pilot phase]. / MS-Register in Deutschland -- Design und erste Ergebnisse der Pilotphase.

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS

Long-term effects of hypothermia on neuronal cell death and the concentration of apoptotic proteins after incomplete cerebral ischemia and reperfusion in rats.

BACKGROUND: The present study investigates the long-term effects of postischemic hypothermia on neuronal cell damage and concentration changes of apoptotic proteins after cerebral ischemia. METHODS: Sixty-four Sprague-Dawley rats were anesthetized, intubated and ventilated with 2.0 Vol% isoflurane and 70% N2O/O2. After preparation the animals were randomly assigned to the following groups: group 1 (n = 32, fentanyl-N2O/normothermia 37.5 degrees C), and group 2 (n = 32, fentanyl-N2O/hypothermia 34.0 degrees C. Ischemia (45 min) was induced by common carotid artery occlusion plus hemorrhagic hypotension (MAP = 40 mmHg). Arterial blood gases and pH were maintained constant. After 1, 3, 7, or 28 days (each n = 8) the brains were removed, frozen and cut. Neuronal damage was assessed by analyzing Bax, Bcl-2, p53, and Mdm-2 proteins, activated caspases-3-positive and eosinophilic cells. A third group (n = 8) of untreated animals served as naive controls. RESULTS: In hypothermic animals, Bax concentration was decreased by 50-70% over time compared to normothermia. On days 1 and 3, Bcl-2 was increased by 50% with hypothermia. The amount of activated caspase-3-positive cells in the ischemic hemisphere was 0.5% in the hypothermic and 1-2% in the normothermic animals. Of the hippocampal cells, 10-25% were eosinophilic in both groups over time. CONCLUSION: The present data show that hypothermia prevents an ischemia-induced increase of the pro-apoptotic protein Bax for as long as 28 days and increases the concentration of the antiapoptotic protein Bcl-2 up to 3 days compared to normothermic animals. Therefore, after cerebral ischemia, hypothermia has the sustained neuroprotective potential to shift apoptosis-related proteins towards neuronal cell survival.

Tryptase inhibits motility of human spermatozoa mainly by activation of the mitogen-activated protein kinase pathway.

BACKGROUND: We previously localized protease-activated receptor 2 (PAR-2) on human spermatozoa and demonstrated that activation of PAR-2 by the mast cell (MC) product tryptase inhibits sperm motility. Importantly, tryptase-secreting MCs are encountered in the male and female genital tract, implying that MC-spermatozoa interactions may be as yet unrecognized factors affecting sperm fertilizing ability. In order to elucidate how tryptase via activation of PAR-2 acts in human spermatozoa, we studied intracellular signal transduction events. METHODS AND RESULTS: Impairment of sperm motility by tryptase was not dependent on the presence of extracellular Ca2+ and tryptase did not alter intracellular Ca2+ levels. Pre-incubation with pertussis toxin (PTX) failed to prevent tryptase effects on sperm motility. Western blot analyses revealed that tryptase increased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2, an effect which was blocked by the MAPK pathway inhibitor PD98059. Pre-treatment of spermatozoa with this inhibitor also blocked the inhibtion of sperm motility evoked by tryptase. CONCLUSIONS: These results indicate that tryptase acts via the ERK1/2 pathway to inhibit motility of human spermatozoa.

Treatment of HCC with pravastatin, octreotide, or gemcitabine--a critical evaluation.

BACKGROUND/AIMS: New perspectives in the treatment of advanced hepatocellular carcinomas have recently been inaugurated with the application of hydroxymethylglutaryl coenzyme A reductase inhibitors i.e. pravastatin, the somatostatin analogue octreotide, or the cytidine analogue gemcitabine. The present study aimed to evaluate these substances in patients with progressive tumor growth. METHODOLOGY: A total of 58 patients either received 3 x 200 microg/day octreotide for 2 months followed by 20mg octreotide LAR every 4 weeks (n=30) or 40-80 mg pravastatin (n=20) or 80-90 mg/m2 gemcitabine over 24 hours weekly in cycles of 4 weeks (n=8). Kaplan-Meier survival curves and the log-rank test were used for univariate comparison of sur vival. RESULTS: The median overall survival of patients receiving octreotide was 5 months, of patients receiving pravastatin 7.2 months and of patients receiving gemcitabine 3.5 months. The difference between the pravastatin and the gemcitabine groups was significant. No WHO grade 3 or 4 side effects were seen in either group of patients. CONCLUSIONS: These results do not confirm those of former studies. Neither pravastatin, nor octreotide, nor gemcitabine did prolong the patients' median overall survival as compared to control groups reported by other authors. New therapeutic strategies have to be found for patients with advanced hepatocellular carcinomas.