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R Zahn

Publications and source records attributed to R Zahn.

At least 73 records · Page 4Linked to original sources

In-hospital mortality of elderly patients with acute myocardial infarction: data from the MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry.

BACKGROUND: Advanced age remains one of the principal determinants of mortality in patients with acute myocardial infarction (AMI). HYPOTHESIS: The aim of this study was to determine the in-hospital outcome of elderly (> 75 years) patients with AMI who were admitted to hospitals participating in the national MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry. METHODS: MITRA is a prospective, observational German multicenter registry investigating current treatment modalities for patients presenting with AMI. All patients with AMI admitted within 96 h of onset of symptoms were included in the MITRA registry. MITRA was started in June 1994 and ended in January 1997. This registry comprises 6,067 consecutive patients with a mean age of 65 +/- 12 years, of whom 1,430 (17%) were aged > 75 years. Patients were compared with respect to patient characteristics, prehospital delays, early treatment strategies, and clinical outcome. RESULTS: In the elderly patient population, the prehospital delay was 210 min, which was significantly longer than that for younger patients (155 min, p = 0.001). Although the incidence of potential contraindications for the initiation of thrombolysis was almost equally distributed between the two age groups (8.7 vs. 8.2%, p = NS), elderly patients (> 75 years) received reperfusion therapy less frequently (35.9 vs. 64.6%) than younger patients. Mortality increased with advanced age and was 26.4% for all patients aged > 75 years. If reperfusion therapy was initiated, in-hospital mortality was 21.8 versus 28.9% in patients aged > 75 years (p = 0.001) and 29.4 versus 38.5% in patients aged > 85 years (p = 0.001). CONCLUSION: In this registry, elderly patients with AMI had a much higher in-hospital mortality than that expected from randomized trials. In MITRA, the mortality reduction with reperfusion therapy was found to be highest in the very elderly patient population.

Age Factors↗

Transfer of patients with acute myocardial infarction for primary or acute angioplasty from hospitals without the facilities to perform angioplasty. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR).

In patients with acute myocardial infarction (AMI) admitted at hospitals without angioplasty facilities there are some subgroups of patients which seem to profit from a transfer to primary or acute angioplasty. However, current clinical practice at such hospitals is unknown. We analyzed the pooled data of the German acute myocardial infarction registries MITRA and the MIR. Angioplasty was not available at 221/271 hospitals (81.5%). Out of 14,487 patients with acute myocardial infarction admitted to these hospitals, 50.1% (7,259/14,487) received thrombolysis at the initial hospital and 3.6% (523/14,487) were transferred. Out of the transferred patients, 55.3% (289/523) were treated with primary angioplasty and 44.7% (234/523) received a combination of thrombolysis and angioplasty. The proportion of transferred patients increased from 1.1% in 1994 to 5.5% in 1998 (p for trend = 0.001). One hundred and four hospitals (47.1%) never transferred patients. Patients transferred for primary angioplasty (289 patients) were compared to patients treated with thrombolysis at the initial hospitals (7,259 patients). Multivariate analysis showed the following independent predictors for transfer of patients for primary angioplasty: contraindications for thrombolysis (OR = 17.9), a non-diagnostic first ECG (OR = 4.0), pre-hospital delay > 6 hours (OR = 2.5), unknown symptom onset of the acute myocardial infarction (OR = 2.0) and anterior wall acute myocardial infarction (OR = 1.6). Heart failure at admission was the only independent predictor not to transfer patients (OR = 0.40). In Germany only 47.1% of hospitals without angioplasty facilities transfer patients with acute myocardial infarction to primary or acute angioplasty. The proportion of transferred patients increased from 1.1% in 1994 to 5.5% in 1998. Contraindications for thrombolysis were the strongest predictor to transfer patients to primary angioplasty.

Aged↗

[Initial experience with an implantable loop recorder in patients with unexplained syncope].

Patients with recurrent syncope undiagnosed after extensive noninvasive and invasive testing pose a diagnostic and therapeutic dilemma. Holter monitoring is non-diagnostic in 90% of cases. Recent developments in loop recorder technology permit longterm ECG monitoring in patients with recurrent unexplained syncope. The implantable loop recorder monitors a single lead electrogram continuously using 2 sensing electrodes on the device shell. The device was implanted in 20 patients (11 male, 9 female) with the history of recurrent syncope. During a mean follow-up of 12+/-6 months after device implantation, 11 patients (55%) experienced syncope (8 pts) or presyncope (3 pts). In the remaining 9 patients, no syncope occurred. In all 11 patients with syncope or presyncope during follow-up, loop recording definitively determined whether an arrhythmia was the cause of symptoms or not. Diagnosis included bradycardia in one patient, tachycardia in two patients, in one patient two rhythm disturbances were revealed: frequent ventricular premature beats with bigemini and atrial flutter. Two patients had a neurocardiogenic syncope. Syncope was nonarrhythmic in 5 patients. An implantable loop recorder is useful for establishing the diagnosis if symptoms are recurrent but too infrequent for conventional monitoring techniques.

Aged↗

Acute myocardial infarction occurring in versus out of the hospital: patient characteristics and clinical outcome. Maximal Individual TheRapy in Acute Myocardial Infarction (MITRA) Study Group.

OBJECTIVES: We describe the baseline characteristics and clinical course of patients who had an acute myocardial infarction (AMI) during their hospital stay. BACKGROUND: In comparison with patients who had an AMI outside of the hospital (prehospital AMI), the data on patients who had an AMI in the hospital are poorly described. METHODS: Patients with an in-hospital AMI were prospectively registered in the Southwest German Maximal Individual TheRapy in Acute myocardial infarction (MITRA) study and compared with patients with prehospital AMI. RESULTS: Of 5,888 patients with AMI, 403 patients (6.8%) had an in-hospital AMI. These patients were older, more often male and sicker as compared with the patients with a prehospital AMI. They also showed a higher prevalence of concomitant diseases, such as arterial hypertension, diabetes mellitus, renal insufficiency and contraindications for thrombolysis. There was no significant difference regarding the use of reperfusion therapy, either thrombolysis (in-hospital AMI 44.2% vs. prehospital AMI 49.1%; odds ratio [OR] 0.86, 95% confidence interval [CI] 0.70 to 1.05) or primary angioplasty (9.9% vs. 8.2%; OR 1.23, 95% CI 0.88 to 1.73), or a combination of both, between the two groups. The interval from symptom onset to the start of treatment in patients receiving reperfusion therapy was 55 min for patients with an in-hospital AMI versus 180 min for patients with a prehospital AMI (p = 0.001). In-hospital death occurred in 110 (27.3%) of 403 patients with an in-hospital versus 762 (13.9%) of 5,485 patients with a prehospital AMI (OR 2.33, 95% CI 1.85 to 2.94). This was confirmed by logistic regression analysis after adjusting for other confounding variables (OR 1.67, 95% CI 1.23 to 2.24). CONCLUSIONS: In-hospital AMI occurred in 6.8% of patients. Time to intervention was shorter; however, the use of reperfusion therapy for in-hospital AMI was not different from that for prehospital AMI. In particular, primary angioplasty seems to be underused in these patients. This, as well as the selection of patients, may result in the high hospital mortality rate of 27.3%.

Aged↗

Decreasing hospital mortality between 1994 and 1998 in patients with acute myocardial infarction treated with primary angioplasty but not in patients treated with intravenous thrombolysis. Results from the pooled data of the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Registry and the Myocardial Infarction Registry (MIR).

OBJECTIVES: We investigated changes in the clinical outcome of primary angioplasty and thrombolysis for the treatment of acute myocardial infarction (AMI) from 1994 to 1998. BACKGROUND: Primary angioplasty for the treatment of AMI is a sophisticated technical procedure that requires experienced personnel and optimized hospital logistics. Growing experience with primary angioplasty in clinical routine and new adjunctive therapies may have improved the outcome over the years. METHODS: The pooled data of two German AMI registries: the Maximal Individual Therapy in AMI (MITRA) study and the Myocardial Infarction Registry (MIR) were analyzed. RESULTS: Of 10,118 lytic eligible patients with AMI, 1,385 (13.7%) were treated with primary angioplasty, and 8,733 (86.3%) received intravenous thrombolysis. Patients characteristics were quite balanced between the two treatment groups, but there was a higher proportion of patients with a prehospital delay of >6 h in those treated with primary angioplasty. The proportion of an in-hospital delay of more than 90 min significantly decreased in patients treated with primary angioplasty over the years (p for trend = 0.015, multivariate odds ratio [OR] for each year of the observation period = 0.84, 95% confidence interval [CI]: 0.73-0.96) but did not change significantly in patients treated with thrombolysis. Hospital mortality decreased significantly in the primary angioplasty group (p = 0.003 for trend; multivariate OR for each year = 0.73, 95% CI: 0.58-0.93). However, for patients treated with thrombolysis, hospital mortality did not change significantly (p for trend 0.175, multivariate OR for each year: 1.02, 95% CI: 0.94- 1.11). CONCLUSIONS: Compared with thrombolysis the clinical results of primary angioplasty for the treatment of AMI improved from 1994 to 1998. This indicates a beneficial effect of the growing experience and optimized hospital logistics of this technique over the years.

Angioplasty, Balloon, Coronary↗

NMR experiments for resonance assignments of 13C, 15N doubly-labeled flexible polypeptides: application to the human prion protein hPrP(23-230).

A combination of three heteronuclear three-dimensional NMR experiments tailored for sequential resonance assignments in uniformly 15N, 13C-labeled flexible polypeptide chains is described. The 3D (H)N(CO-TOCSY)NH, 3D (H)CA(CO-TOCSY)NH and 3D (H)CBCA(CO-TOCSY)NH schemes make use of the favorable 15N chemical shift dispersion in unfolded polypeptides, exploit the slow transverse 15N relaxation rates of unfolded polypeptides in high resolution constant-time [1H, 15N]-correlation experiments, and use carbonyl carbon homonuclear isotropic mixing to transfer magnetization sequentially along the amino acid sequence. Practical applications are demonstrated with the 100-residue flexible tail of the recombinant human prion protein, making use of spectral resolution up to 0.6 Hz in the 15N dimension, simultaneous correlation with the two adjacent amino acid residues to overcome problems associated with spectral overlap, and the potential of the presently described experiments to establish nearest-neighbor correlations across proline residues in the amino acid sequence.

Carbon Isotopes↗

NMR analysis of the binding of a rhodanese peptide to a minichaperone in solution.

A detailed structural analysis of interactions between denatured proteins and GroEL is essential for an understanding of its mechanism. Minichaperones constitute an excellent paradigm for obtaining high-resolution structural information about the binding site and conformation of substrates bound to GroEL, and are particularly suitable for NMR studies. Here, we used transferred nuclear Overhauser effects to study the interaction in solution between minichaperone GroEL(193-335) and a synthetic peptide (Rho), corresponding to the N-terminal alpha-helix (residues 11 to 23) of the mitochondrial rhodanese, a protein whose in vitro refolding is mediated by minichaperones. Using a 60 kDa maltose-binding protein (MBP)-GroEL(193-335) fusion protein to increase the sensitivity of the transferred NOEs, we observed characteristic sequential and mid-range transferred nuclear Overhauser effects. The peptide adopts an alpha-helical conformation upon binding to the minichaperone. Thus the binding site of GroEL is compatible with binding of alpha-helices as well as extended beta-strands. To locate the peptide-binding site on GroEL(193-335), we analysed changes in its chemical shifts on adding an excess of Rho peptide. All residues with significant chemical shift differences are localised in helices H8 and H9. Non-specific interactions were not observed. This indicates that the peptide Rho binds specifically to minichaperone GroEL(193-335). The binding region identified by NMR in solution agrees with crystallographic studies with small peptides and with fluorescence quenching studies with denatured proteins.

ATP-Binding Cassette Transporters↗

Primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients not included in randomized studies. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

Patients with acute myocardial infarction included in randomized trials comparing primary percutaneous transluminal coronary angioplasty (pPTCA) with thrombolysis represent a special subgroup of patients with a low event rate. Patients excluded from these trials represent a variety of different subgroups, with different patient characteristics and possibly different clinical event rates. Primary PTCA was performed in 491 consecutive patients with acute myocardial infarction in the prospective multicenter observational Maximal Individual Therapy in Acute Myocardial Infarction trial. They were divided into the following groups: group I, patients fulfilling the inclusion criteria of the randomized trials (284 of 491, 58%); group II, patients not included in these trials (207 of 491, 42%). Of group II the following subgroups were defined: group IIa, patients in cardiogenic shock (20 of 491, 4.1%); group IIb, patients with a left bundle branch block (12 of 491, 2,4%); group IIc, patients with contraindications for thrombolysis (42 of 491, 8.6%); group IId, patients with a nondiagnostic first electrocardiogram (95 of 491, 19.3%); group IIe, patients with a prehospital delay of > 12 hours (72 of 491, 14.7%); group IIf, patients with an unknown prehospital delay (30 of 491, 6.1%). A comparison of groups I and II showed similar baseline characteristics but a higher clinical event rate during hospitalization was seen in group II: combined end point of death, reinfarction, heart failure equal to or greater than NYHA class III, any stroke or postinfarction angina, 26.6% versus 18%; p = 0.022. Hospital deaths were nearly twice as high in these patients, without reaching statistical significance (10.6% vs 6%; p = 0.06). The subgroups of group II showed quite different rates of clinical events. In-hospital death rates were: IIa, 40% (8 of 20); IIb, 8% (1 of 12); IIc, 12% (5 of 42); IId, 5% (5 of 95); IIe, 6% (4 of 72); and IIf, 13% (4 of 30). The incidence of the combined end point was 60% (12 of 20) in IIa, 33% (4 of 12) in IIb, 29% (12 of 42) in IIc, 16% (15 of 95) in IId, 26% (19 of 72) in IIe, and 33% (10 of 30) in IIf. Thus, in clinical practice, about half of the patients treated with pPTCA would not have been included in randomized trials comparing pPTCA with thrombolysis. These patients represent a population at higher risk for in hospital clinical events. However, they do represent very different nonhomogenous subgroups with different clinical event rates.

Aged↗

Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases.

Bone marrow (BM) is a clinically relevant site of micrometastatic disease in patients with solid epithelial tumors. It is, therefore, important to establish suitable models that allow the in-depth characterization of disseminated tumor cells present at low frequencies of 10(-5)-10(-6) nucleated BM cells. The aim of this study was to assess common phenotypic features of nine tumor cell lines established from BM of patients with cancer of the prostate (four cell lines), breast (two cell lines), lung (two cell lines), and colon (one cell line) using immunocytochemistry, flow cytometry, and reverse transcription-PCR. All cell lines stained positive for both cytokeratins, the epithelial intermediate filaments, and the epithelial cell adhesion molecule E-cadherin, and they lacked markers of BM-derived cells. The tumor origin of the cell lines was supported by the expression of the ErbB2 oncogene (seven of nine) and MAGE mRNA (eight of eight). All cell lines coexpressed cytokeratin and vimentin, the mesenchymal intermediate filament, indicating an epithelial-mesenchymal transition of micrometastatic cells. The invasive phenotype of the immortalized cells was also reflected by the consistent expression of several metastasis-associated adhesion molecules, including alpha5 (eight of nine), alpha6 (five of nine), alphaV (nine of nine), beta1 (nine of nine), and beta3 (nine of nine) integrin subunits and the Mr 67,000 laminin receptor (seven of nine). Contrary to our expectations, metastasis-promoting CD44 variant isoforms were only detected on two lines, whereas all cell lines expressed MUC18/melanoma cell adhesion molecule and intercellular adhesion molecule-1, two members of the immunoglobulin superfamily of adhesion molecules that are not frequently found on primary carcinoma cells. The consistent expression of various epithelial and tumor-associated antigens provides evidence that the established cell lines are derived from disseminated cancer cells present in the BM. The invasive phenotype of the immortalized cells was mirrored by their epithelial-mesenchymal transition and the expression of several metastasis-associated molecules, which might be potential candidates for novel therapeutic targets.

Biomarkers, Tumor↗

Peptides and proteins in neurodegenerative disease: helix propensity of a polypeptide containing helix 1 of the mouse prion protein studied by NMR and CD spectroscopy.

Transmissible spongiform encephalopathies (TSE) or "prion diseases" have been related to the "protein-only hypothesis", which suggests that the "scrapie form (PrPSc)" of the prion protein (PrP) is the TSE infectious agent. The nmr structure of the ubiquitous benign cellular form of PrP (PrPC) consists of a globular domain of residues 126-231 with three alpha-helices and a short beta-sheet, and a flexible extended "tail" of residues 23-125. The peptide segment of helix 1 has been implicated in various stages of hypothetical pathways to prion pathology on the basis of the protein-only idea, including that it takes part in the conformation change that leads from PrPC to PrPSc. In this paper we describe solution nmr and circular dichroism studies of the synthetic hexadecapeptide mPrP(143-158), with the sequence H-NDWEDRYYRENMYRYP-NH2, where the bold letters represent the segment that forms helix 1 in murine PrPC. In both H2O and a 1:1 mixture of H2O and trifluoroethanol this polypeptide segment shows high helix propensity, which is a key issue in discussions on potential roles of this molecular region in conformational transitions of PrP.

Amino Acid Sequence↗

Comparison of primary angioplasty with conservative therapy in patients with acute myocardial infarction and contraindications for thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

The benefit of primary angioplasty in patients with acute myocardial infarction (AMI) and contraindications for thrombolysis compared to a conservative regimen is still unclear. Out of 5,869 patients with AMI registered by the MITRA trial, 337 (5.7%) patients had at least one strong contraindication for thrombolytic therapy. Out of these 337 patients 46 (13.6%) were treated with primary angioplasty and 276 (86.4%) were treated conservatively. Patients treated conservatively were older (70 years vs. 60 years; P=0.001), had a higher rate of a history with chronic heart failure (14.8% vs. 4.4%; P=0.053), a higher heart rate at admission (86 beats/min vs. 74 beats/min; P=0.001), and a higher prevalence of diabetes mellitus (27.1% vs. 12.8%; P=0.056). Patients treated with primary angioplasty received more often aspirin (91.3% vs. 74.6%; P=0.012), beta-blockers (60.9% vs. 46.1%; P = 0.062), angiotensin converting enzyme (ACE) inhibitors (71.7% vs. 44%; P=0.001), and the so-called optimal adjunctive medication (54.4% vs. 32.3%; P=0.004). Hospital mortality was significantly lower in patients who received primary angioplasty (univariate: 2.2% vs. 24.7%; P=0.001; multivariate: OR=0.46; P=0.0230). In patients with AMI and contraindications for thrombolytic therapy, primary angioplasty was associated with a significantly lower mortality compared to conservative treatment. Therefore, hospitals without the facilities to perform primary angioplasty should try to refer such patients to centers with the facilities for such a service, if this is possible in an acceptable time.

Aged↗

Differences in patients with acute myocardial infarction treated with primary angioplasty or thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

BACKGROUND: Little is known about the differences in patients with acute myocardial infarction (AMI) treated with primary angioplasty or intravenous thrombolysis in clinical practice. METHODS: In all, 5,906 patients with AMI were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Of these, 491 (8.3%) patients were treated with primary angioplasty and 2,817 (47.7%) with intravenous thrombolysis. RESULTS: There were only minor differences in baseline characteristics between the two groups. Prehospital delay time (median) was longer in the angioplasty group than in the thrombolysis group (161 vs. 120, p = 0.001), as was door-to-treatment time (88 vs. 30 min; p = 0.001). Patients treated with primary angioplasty more often had contraindications for thrombolytic therapy (12.9 vs. 6%, p = 0.001) and received beta blockers (65 vs. 58.1%, p = 0.004), heparin (98.2 vs. 91.6%, p = 0.001), angiotensin-converting enzyme (ACE) inhibitors (64.8 vs. 50%, p = 0.001) and "optimal" concomitant medication (56.4 vs. 42.9%, p = 0.001) more often. Univariate analysis showed a significant lower incidence of heart failure (5.3 vs. 16.5%, p = 0.001), postinfarct angina (7.3 vs. 16.4%, p = 0.001), in-hospital death (7.9 vs. 11.7%, p = 0.015) and the combined end point (21.6 vs. 40.3%, p = 0.001) in these patients. Stepwise logistic regression analysis revealed optimal concomitant medication [odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-0.98) and the type of revascularization (OR = 0.65, 95% CI: 0.58-0.73) to be associated with a significant reduction in the incidence of the combined end point. Similar results were obtained in all predefined subgroups. CONCLUSIONS: In clinical practice, patients treated with primary angioplasty are more often treated with beta blockers and ACE inhibitors than patients treated with intravenous thrombolysis. Thus, the selection of patients and the type of revascularization contributes to the reduction in mortality, overt heart failure, and postinfarct angina in these patients.

Angioplasty, Balloon, Coronary↗

[Primary dilatation versus thrombolysis in patients with acute myocardial infarct, not included in randomized studies. Results of the MITRA Study. Maximal Individual Optimized Therapy for Acute Myocardial Infarct].

There have been some prospective randomized studies which compared primary angioplasty with intravenous thrombolysis in patients with an acute myocardial infarction (AMI). However, a substantial number of patients with AMI who would not have been included in those trials are treated with one of these two therapeutic options. To describe the proportions, characteristics, and outcome of these patients treated with primary angioplasty or thrombolysis we analyzed the data of the prospective "Maximal Individual Optimized Therapy for Acute Myocardial Infarction" (MITRA) trial. Out of 3308 patients treated with primary angioplasty or thrombolysis, 737 (22.3%) belonged to one of the following groups, not included in current randomized trials: Left bundle branch block, non-diagnostic first ECG, pre-hospital delay > 12 hours or unknown pre-hospital delay. Primary angioplasty was performed in 158/737 (21.4%) and thrombolysis received 579/737 (78.6%) of the patients. There were only minor differences regarding patients' characteristics and concomitant diseases between the two groups. Patients treated with primary angioplasty were 3 years younger (62 years median versus 65 years median (p < 0.036). They also more often showed overt heart failure at admission compared to patients treated with thrombolysis (primary angioplasty: 3.2% versus thrombolysis: 8.9%, OR = 0.34, 95% CI: 0.13-0.86). In-hospital time to intervention was 1 1/2 hours longer in patients treated with primary angioplasty (156 minutes median versus 47 minutes median, p = 0.001). beta-blockers were more often used with primary angioplasty compared to thrombolysis (70.31% versus 55.9%; OR = 1.87, 95% CI: 1.28-2.72), as well as ACE inhibitors (62% versus 49.9%; OR = 1.64, 95% CI: 1.14-2.35). Hospital mortality (8.2% versus 16.4%; OR = 0.46, 95% CI: 0.25-0.84), as well as a combined endpoint of death, reinfarction, postinfarction angina, advanced heart failure, and stroke (24.1% versus 42.3%, OR = 0.43, 95% CI: 0.29-0.64) were lower in patients treated with primary angioplasty compared to those treated with thrombolysis. Logistic regression analysis showed primary angioplasty to be independently associated with a lower rate of the combined endpoint (OR = 0.73, 95% CI: 0.59-0.91), after adjusting for confounding parameters. All subgroups showed a more favorable outcome in patients treated with primary angioplasty. In clinical practice, patients with AMI, not included in current randomized trials comparing primary angioplasty with thrombolysis, account for 22% of all patients with AMI treated with one of those two therapies. Primary angioplasty seems to be associated with a lower event rate compared to thrombolysis in these patients. This has to be confirmed by a prospective randomized trial.

Aged↗

Daytime and nighttime differences in patterns of performance of primary angioplasty in the treatment of patients with acute myocardial infarction. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

BACKGROUND: Concern exists regarding the results of primary angioplasty for acute myocardial infarction when the procedure is performed during night hours. METHODS AND RESULTS: Between June 1994 and January 1997, 491 patients with acute myocardial infarction who underwent primary angioplasty procedures were consecutive registered in the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Three hundred seventy-eight patients (77%) were treated during the day and 113 (23%) at night. Baseline characteristics showed no major differences between the 2 groups. Prehospital delay time was 60 minutes shorter during the night (median value 180 minutes for day, 120 minutes for night, P =.005), and in-hospital time to treatment was 9 minutes longer (median value 85 minutes day, 94 minutes night, P =.037). Patients treated during the night more often received angiotensin-converting enzyme blockers (61.4% day, 76.1% night, P =.004) and the so-called optimal adjunctive therapy (54% day, 64.6% night, P =.045). There were no differences concerning clinical events between the 2 groups. Hospital mortality was 8.7% during the day and 5.3% during the night (univariate analysis P =.238; logistic regression P =.653). CONCLUSIONS: In a clinical setting, primary angioplasty for acute myocardial infarction can be performed safely during the night with a clinically insignificant prolongation of in-hospital time to reperfusion compared with practice during the day.

Aged↗

Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism.

BACKGROUND: Thrombolytic agents are given in massive pulmonary embolism to dissolve or reduce the clot and normalize hemodynamics. Comparative clinical studies have shown that administration of a 2-hour infusion of alteplase is more effective than urokinase over a 12-hour period. Reteplase is a new generation thrombolytic with a longer half-life that can be administered more conveniently as a double bolus. We compared efficacy and safety of reteplase with the approved regimen of alteplase in massive pulmonary embolism. METHODS: Thirty-six patients were enrolled and randomly assigned: 23 received reteplase and 13 received alteplase along with intravenous heparin. Reteplase was administered as 2 intravenous bolus injections of 10 U 30 minutes apart, and alteplase was administered as an intravenous infusion of a total dose of 100 mg over a 2-hour period, including an initial 10-mg bolus. Diagnosis of pulmonary embolism was confirmed by selective pulmonary angiography. Hemodynamic monitoring was conducted during the first 24 hours after administration. The primary end point was change in total pulmonary resistance. Secondary variables were pulmonary pressure, cardiac index, clinical parameters, and adverse events. RESULTS: The primary parameter of total pulmonary resistance showed a significant decrease after just 0.5 hours in the reteplase group and after 2 hours in the alteplase group, with a further decrease persisting for up to 24 hours in both treatment groups. A similar pattern was seen in other directly measured hemodynamic parameters, especially mean pulmonary artery pressure and cardiac index; there was no significant difference between reteplase and alteplase. There was also no apparent difference between the treatment groups with respect to safety, and no stroke or intracranial hemorrhage occurred. The rate of bleedings and the incidence of nonhemorrhagic adverse events were as expected for patients with pulmonary embolism treated with a thrombolytic agent. CONCLUSIONS: Reteplase is suitable for treatment of massive pulmonary embolism with a standard double bolus 10 + 10 U. Efficacy of reteplase appeared to be at least as good at decreasing pulmonary vascular resistance as that of the approved alteplase regimen of 100 mg infusion over a 2-hour period.

Adult↗

Unusual association of the DRB4 null allele, DRB4*0103102N, with HLA DRB1*0402 in a sample of Austrian patients.

Tissue typing for HLA class II antigens is routinely performed by serological, and/or DNA-based methods. Accuracy, absence of cross-reactivity and controllable level of resolution are striking advantages of molecular methods. However, a disadvantage of molecular typing, compared to serological methods, is the identification of unexpressed alleles. Whereas serology allows a more or less direct insight into antigen presence, molecular biology is an indirect method and results must also be interpreted by considering the biological pathways of protein expression. We believe that identification of nonexpressed MHC alleles is of importance for transplantation, since nonexpressed MHC allele positive individuals could give rise to antibody formation against the respective expressed MHC product in donor tissue. Usually, the nonexpressed DRB4*0103102N is encountered in association with DRB1*0701-DQB1*03032, which facilitates correct DNA typing. Here we describe the unusual association of this unexpressed DRB4*0103102N, with DRB1*0402-DQB1*0302 in a sample of Austrian patients.

Adult↗

Virtual DNA analysis as a platform for interlaboratory data exchange of HLA DNA typing results.

In 1998, the German DNA Exchange offered the possibility to report typing data as virtual DNA. Participating labs have been equipped with software based on the principle of Virtual DNA Analysis (VDA). This approach allows the combination of sequence-specific oligonucleotide (SSO), sequence-specific primer (SSP) and sequence-based typing (SBT) results. The use of all types of test kits has been allowed without any limitations, as long as basic sequence information on SSOs or SSPs was available, at least the sequence and the position of the detected motif on the sample DNA. Typing raw data of the actual SSO-SSP and, if performed, SBT information was collected. Participating labs received 20 DNA samples to type. Fourteen labs returned data on 1,250 single-locus testings. Reported data consisted of 317 SBT data, 452 SSO kits and 1,795 SSP kits with 43,312 single SSO/ SSP reactivities. One hundred and twenty-six different typing kits (unique laboratory-specific kits, commercial kits from 7 companies) have been used. In 30 (2.4%) single-locus testings, at least one single SSO/SSP reactivity has been false-positive or -negative, thus not leading to a valid result on primary evaluation. Eight of these 30 cases were due to the presence of a new DRB1*14 allele in sample no. 2. Thirty-five tests (2.8%) showed wrong allele assignments. This first attempt to collect raw typing data instead of typing interpretation on a larger scale shows the advantages of Virtual DNA Analysis like interlaboratory data exchange without loss of information, transparency of typing interpretation and reinterpretation of typing data with an updated allele database. The VDA format is a useful tool for workshops and bone marrow donor registries.

Alleles↗