Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence- activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis.     

Effect of adding albumin to solutions of somatostatin on inhibiting pentagastrin-stimulated acid secretion in dogs

In five conscious dogs with chronic gastric fistulas we studied the effect of somatostatin solutions on pentagastrin-stimulated acid secretion. Somatostatin was dissolved in 0.154 M NaCl alone or in the same amount of saline to which dog albumin had been added to give a 0.5% solution. Somatostatin produced a dose-dependent inhibition of pentagastrin-stimulated gastric secretion. However, the inhibition was significantly less when somatostatin was dissolved in saline as compared to saline plus albumin. This study suggests that albumin should be added to somatostatin solutions to preserve biological activity, and it confirms previous reports indicating that, without albumin, basic peptides have a tendency to stick to infusion systems.     

Too little aspirin for secondary prevention after acute myocardial infarction in patients at high risk for cardiovascular events: Results from the MITRA study

Background

A meta-analysis of randomized trials has shown a significant reduction of mortality rate in patients receiving aspirin for secondary prevention after acute myocardial infarction (AMI). However, a significant number of patients do not receive aspirin after AMI. Little is known about why aspirin is withheld or the long-term outcome of these patients today.

Methods

The Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) registry is a multicenter registry of patients with AMI in Germany.

Results

Of 4902 patients, 509 (10%) did not receive aspirin at the time of discharge from the hospital. The mean follow-up period for these patients was 17 months. Relative contraindications to aspirin were significantly associated with the withholding of aspirin (in-hospital bleeding: odds ratio [OR], 3.56; 95% CI, 1.86-6.80; history of peptic ulcer: OR, 2.49; 95% CI, 1.62-3.83). Absolute contraindications to aspirin were rare (2.2%). Other medications of proven benefit were also given less often in these patients (β-blockers: 49.0% vs 61.9%, P <.001; angiotensin-converting enzyme inhibitors: 65.6% vs 70.2%, P = .06; statins: 12.2% vs 15.1%, P = .10). Patients who were not given aspirin were at high risk for vascular events. They were more likely to have a history of prior AMI (OR, 1.34; 95% CI, 1.02-1.79), were in critical clinical condition at admission more often (cardiogenic shock: OR, 1.98; 95% CI, 1.09-3.56; overt heart failure: OR, 1.6; 95% CI, 1.05-2.3), and received acute revascularization less often (OR, 1.32; 95% CI, 1.05-1.67). The 1-year mortality was 2-times higher in patients who did not receive aspirin than in patients who did receive aspirin (16.5% vs 8.3%, P <.001). A significant association of withheld aspirin at discharge with a higher long-term mortality rate was confirmed with multivariate analysis (OR, 1.62; 95% CI, 1.15-2.29).

Conclusions

Ten percent of patients who sustained an AMI did not receive aspirin at the time of hospital discharge. Most of these patients were at high risk for cardiovascular events. Withheld aspirin was significantly associated with higher mortality rate during follow up.     

Insufficient tissue ablation by rotational atherectomy leads to worse long-term results in comparison with balloon angioplasty alone for the treatment of diffuse in-stent restenosis: insights from the intravascular ultrasound substudy of the ARTIST randomized multicenter trial.

The ARTIST trial demonstrated a worse outcome for patients with in-stent restenosis (ISR) treated with rotational atherectomy (RA) and adjunctive balloon angioplasty (PTCA) as compared to PTCA alone. This intravascular ultrasound (IVUS) substudy compares effects of lumen enlargement and examines reasons for failure of RA in this setting. IVUS (n = 56) was performed after each interventional step and at follow-up. Volumetric lumen gain measured 79 +/- 68 mm(3) after PTCA (13 +/- 4 atm) as compared to 44 +/- 26 mm(3) after RA and adjunctive PTCA (7 +/- 3 atm; P < 0.0001). RA itself enlarged lumen by only 19 +/- 17 mm(3) and stent volume was 47% smaller as compared to high-pressure PTCA. Low-pressure strategy after RA did not prevent tissue growth during follow-up (19 +/- 25 vs. 36 +/- 38 mm(3); RA vs. PTCA; P = 0.09). Consequently, net lumen gain after PTCA was 82% higher compared to RA (46 +/- 54 vs. 25 +/- 24 mm(3); P = 0.09). Further stent expansion is the key mechanism to achieve luminal gain by PTCA of ISR. Neointimal ablation by RA has only minor effects. Low-pressure PTCA does not prevent recurrent tissue growth and failed for treatment of ISR due to insufficient stent expansion.     

Early time course of neointima formation and vascular remodelling following percutaneous coronary intervention and vascular brachytherapy of in-stent restenotic lesions as assessed by intravascular ultrasound analysis

Summary In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up.By QCA the acute lumen gain measured 2.2±0.8 mm, the late lumen loss at 3 months was 0.1±0.5 mm and at 6 months 0.4±0.7 mm. By IVUS luminal cross-sectional area increased from 1.5±1.2 mm² to 7.9±1.9 mm² (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2±1.0 mm² (p=0.191), but increased to 0.7±0.6 mm² (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1±1.7 mm². Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3±1.9 mm² (p<0.001), and showed a further increase by 0.7±2.9 mm² at 6 months. Positive remodelling could be demonstrated also at the reference segment.In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.Diese Publikation enthält die Ergebnisse der Promotionsarbeit von Frau Andrea Zimmermann     

Impact of ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation acute myocardial infarction

We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27).     

Prehospital delay-not just a question of patient knowledge

Patients with acute myocardial infarction reaching the hospital within the first hour after symptom onset preserve their chances for an optimal treatment. But only about one fifth of them actually reach the hospital within this "golden hour". Information of the public to reduce time from symptom onset to medical service call have shown success only during the time the continuous publicity was maintained. Soon after the end of such activities the prehospital delay again reached the initial duration. Because of restricted resources, prehospital thrombolysis as another means of reducing time to treatment is as yet only used for a very small proportion of patients. Reduction of door-to-balloon and -treatment time seems to have reached its limit in recent years. In patients with delayed hospital admission, the use of PTCA interventions seems to result in better outcome data compared to thrombolysis.     

Measuring pressure-derived fractional flow reserve through four French diagnostic catheters

Measurement of fractional flow reserve (FFR) with a pressure wire is used to discriminate between patients with and without functionally significant lesions. FFR can be assessed through a conventional 4Fr diagnostic catheter, which is a more convenient method of assessment. The aim of this study was to assess the feasibility, safety, repeatability, and reliability of routine FFR measurements through 4Fr diagnostic catheters. From a single-center prospective registry, results of FFR assessment through a 4Fr catheter were used to determine: (1) feasibility and safety, by the procedural success rate and immediate and 30-day clinical outcome; (2) repeatability, by the intraclass correlation coefficient and comparison of the difference (means +/- 2 SDs); and (3) reliability, by comparison of results obtained using 4Fr versus 7Fr guiding catheters. During the study period, FFR was measured in 190 patients, in 122 using a diagnostic 4Fr catheter (study population) and in 68 using a 7Fr guiding catheter. Measurement of FFR wa successful in 115 of 122 patients (94%). No complications related to the use of the 4Fr catheter occurred. Repeatability was determined from 108 repeated measurements: the intraclass correlation coefficient was 0.942 and the mean difference between repeated FFR measurements was -0.001 +/- 0.038. Reliability was determined from 15 unselected patients; there was no systematic error and only 1 value was out of the range of 2 SDs of the mean difference. Using a threshold value of 0.75, the Kappa coefficient for the qualitative agreement was 0.84. Thus, pressure-derived FFR assessment can safely be performed through 4Fr diagnostic catheters, with similar repeatability and reliability as 7Fr guiding catheters, resulting in a simplification of the measurement procedure.     

Small differences in non-fatal in-hospital reinfarctions complicating acute myocardial infarction as observed in current randomised controlled trials will not essentially influence long-term mortality. Results from the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry

BACKGROUND: Recent randomized controlled trials (RCT) comparing different nonmechanical reperfusion strategies in patients with acute ST elevation myocardial infarction (AMI) (The GUSTO V, the ASSENT 3 and the HERO 2 trials) reported no differences in mortality, but lower nonfatal reinfarction rates in each best treatment arm during the hospital stay. METHODS: We analyzed the prospective observational Maximal Individual The rapy in Acute Myocardial Infarction (MITRA) data base selecting AMI patients similar to the RCT patients, to determine whether the observed differences in reinfarction rates will have an influence on longterm mortality. RESULTS: Out of 6737 patients included in MITRA between 1994 and 2000, 2109 (31%) fulfilled the selection criteria simulating the RCTs and were followed up for a median of 18 (quartiles: 16/22) months. Mortality at 1-year after discharge was 6.8% (95%CI: 2.3-11.3%) in patients with versus 4.4% (95%CI: 3.5-5.3%) in patients without a non-fatal reinfarction (absolute difference 2.4%, p = 0.04 by log rank test). Transferred to the results of the RCTs, this difference would require more than 1 million patients in each treatment arm of the RCTs to show significant differences in long-term mortality. CONCLUSION: Non-fatal in-hospital reinfarctions were associated with a higher mortality during the 18 month follow-up in MITRA. However, because the observed differences in the rates of non-fatal in hospital reinfarctions between the treatment arms in the GUSTO V, the ASSENT 3 and the HERO 2 trials were very small, our data make it very improbable that they will result in lower 1-year mortality rates.