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Biomedical subjects

E Raeder

Publications and source records attributed to E Raeder.

13 recordsLinked to original sources
PubMed1994

Altered surface marker expression and function of G-CSF-induced neutrophils from test subjects and patients under chemotherapy.

We have previously reported an altered surface marker expression and chemotaxis of G-CSF-induced neutrophils from patients with severe congenital neutropenia. However, effects of G-CSF and influence of the underlying disease on neutrophils could not be discerned. In this study we have evaluated the effects of G-CSF on neutrophil phenotype and function in patients under chemotherapy and in healthy test subjects. We found a significantly enhanced expression of Fc gamma RI, CD14 and CD54 and a decrease in the level of Fc gamma RIII during G-CSF treatment. In addition, motility of G-CSF-induced neutrophils was significantly decreased. The effects were seen in patients under cytotoxic chemotherapy and in healthy test subjects. Surface marker alterations and neutrophil motility were affected by G-CSF administration in a dose-dependent manner. Kinetic studies on neutrophils from healthy test subjects demonstrated that all effects could be seen after a single administration of 300 micrograms G-CSF and began to appear within 4 h. Release of partially immature neutrophils from the bone marrow and indirect activation of these cells by G-CSF are discussed as possible reasons for the findings presented. They demonstrate that G-CSF has profound effects on neutrophil phenotype and function in vivo which might have clinical implications.

Antigens, Surface↗
PubMed1994

Changes in light-scatter profile, membrane depolarization and calcium mobilization of neutrophils induced by G-CSF in vivo.

To extend our studies about phenotypical and functional alterations of G-CSF-induced neutrophils we have evaluated their light-scatter profile, mobilization of intracellular calcium ([Ca2+]i) and membrane depolarization after stimulation. A significant increase in the forward scatter signals could be demonstrated in such neutrophils from patients with neutropenias of various origin and from healthy test subjects. This increase began 4 h and returned to normal 96 h after G-CSF injection in the latter group. We found an impairment of [Ca2+]i mobilization in neutrophils from patients with glycogen storage disease type IB after stimulation of these cells with fMLP. It was even more pronounced than in severe congenital neutropenia (SCN). However, [Ca2+]i fluxes were normal when ionomycin was used. Neutrophils from patients with cyclic neutropenia (cyNP) and chemotherapy-induced neutropenia (chNP) mobilized [Ca2+]i similar to those from healthy donors. Furthermore, we found a decreased percentage of neutrophils depolarizing after stimulation with fMLP and PMA in patients with SCN, whereas membrane depolarization was normal in patients with chNP and cyNP. All the alterations found here are suggested to be caused by a partial immaturity of the neutrophils, although in vivo activation and a direct effect of G-CSF on myeloid precursors might be involved.

Calcium↗
PubMed1993

Production of oxygen radicals by fibroblasts and neutrophils from a patient with x-linked chronic granulomatous disease.

Recently, a superoxide-generating NADPH-oxidase system in human fibroblasts has been described. Therefore, we reassessed the possible use of this cell type for prenatal diagnosis of CGD patients comparing normal and CGD peripheral blood neutrophils (PMN) and skin fibroblasts in their reactive oxygen intermediate (ROI)-producing capacity. While PMN of the CGD patient showed a clearly reduced respiratory burst activity, which correlated well with the measured content of cytochrome b558, fibroblasts of the same individual showed no impaired production of superoxide anion or H2O2 upon stimulation by cytokines (TNF and IL-1) or other agents (Ca2+ ionophores and PAF, unpublished results). Furthermore, fibroblasts of the CGD patient or of normal donors could be inhibited in ROI production by diphenylene iodonium (DPI) and 2-iodobiphenyl. In contrast to PMN, no inhibition of the fibroblast NADPH-oxidase system was observed using staurosporin, an inhibitor of proteinkinase C. These data demonstrate, in contrast to previous studies, that fibroblasts are able to produce ROI. Nevertheless, since fibroblasts obtained from a CGD patient exhibited no difference in ROI production compared with fibroblasts obtained from healthy donors, they are not suitable for prenatal diagnosis of CGD.

Calcimycin↗
PubMed1991

Effects of milrinone on left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Left ventricular remodeling after an acute myocardial infarction may result in progressive left ventricular dilation that may be associated with increased mortality. We studied the effects of the phosphodiesterase inhibitor milrinone on left ventricular remodeling after acute myocardial infarction. METHODS AND RESULTS: Rats (n = 90) were randomized to undergo either left coronary artery ligation or sham operation. Three weeks after surgery, rats received either no treatment or milrinone, which was continued until 2 days before the rats were killed. Ninety days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically. Compared with untreated infarcted rats, milrinone-treated infarcted rats had a lower left ventricular end-diastolic pressure (1.7 +/- 0.4 versus 4.3 +/- 1.4 mm Hg, p less than 0.05), a lower left ventricular volume (1.25 +/- 0.20 versus 2.37 +/- 0.30 ml/kg, p less than 0.001) and a lower left ventricular wall stress index (1.3 +/- 0.2 versus 1.7 +/- 0.1, p less than 0.05). Left ventricular chamber stiffness was higher in milrinone-treated infarcted rats than in untreated infarcted rats. Milrinone had no cardiac effect on uninfarcted animals. CONCLUSION: Chronic milrinone therapy after acute myocardial infarction improves cardiac hemodynamic indexes and attenuates progressive left ventricular dilation.

Animals↗
PubMed1988

The effect of intracoronary lidocaine on ventricular arrhythmia in the infarcted canine heart.

The efficacy of intracoronary administration of lidocaine was studied in three groups of dogs with experimental myocardial infarction induced by occlusion of the left anterior descending coronary artery (LAD). Group 1 included 14 anesthetized and group 2, 7 conscious animals to which lidocaine 1.4 micrograms/kg/minute was administered as an intracoronary infusion. Group 3 consisted of 17 anesthetized dogs that received an intracoronary bolus of lidocaine 40 micrograms/kg over 30 seconds. In group 1, lidocaine reduced ventricular arrhythmia by 59 +/- 30% (p less than 0.001), whereas systemic lidocaine achieved a reduction by 61 +/- 37% (p 0.06). In seven dogs, lidocaine blood levels were measured in the great cardiac and femoral veins. At the end of the infusion the drug concentration was 3.4 +/- 2.2 micrograms/ml in the great cardiac and 1.3 +/- 1.1 micrograms/ml in the femoral vein (p less than 0.05). The reduction in ventricular arrhythmia correlated with the great cardiac vein lidocaine concentration (r = 0.70; p less than 0.05), but not with the drug level in the femoral vein (r = 0.06; NS). In group 2, lidocaine was ineffective by both routes of administration. This may have been related to higher sympathetic activity, as suggested by an elevated heart rate in conscious compared to anesthetized animals (186 +/- 6 vs 164 +/- 21 bpm; p 0.0054). In group 3, bolus injections of lidocaine into the LAD reduced ventricular arrhythmia by 66% (p 0.001). We conclude that by perfusing the infarcted zone with lidocaine, a significant antiarrhythmic effect can be achieved with 2% of the systemic dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Safety and efficacy of encainide for malignant ventricular arrhythmias.

The antiarrhythmic effect of encainide was evaluated in 140 patients with documented symptomatic ventricular tachycardia or ventricular fibrillation refractory to conventional agents. In 102 patients with reproducible spontaneous arrhythmia, noninvasive methods, including ambulatory monitoring and exercise testing, were used to evaluate drug efficacy, while in the remaining 38 patients electrophysiologic testing was performed. Side effects necessitated drug discontinuation in 10 patients before noninvasive evaluation. Of the remaining 92 patients 44 (48%) responded to encainide. Of the 38 patients who underwent electrophysiologic study, 1 discontinued encainide because of side effects and in 4 patients the spontaneous occurrence of sustained ventricular tachycardia precluded repeat study. Of the remaining 33 patients, 10 (30%) were rendered noninducible with encainide. The drug was more effective in those with a left ventricular ejection fraction greater than 35% (p less than 0.03) and in those presenting with nonsustained ventricular tachycardia. Side effects were reported in 53 of 140 patients (38%) and were primarily nausea, vomiting, headaches and tremors. Aggravation of arrhythmia occurred in 4% of patients with a history of nonsustained arrhythmia and in 25% of those with a history of sustained ventricular tachycardia or ventricular fibrillation. Worsening of arrhythmia was not related to mean dose of drug, mean blood level or electrocardiographic changes; it was more likely to occur in patients with a markedly reduced left ventricular ejection fraction (average 32%) and in those with a history of sustained ventricular tachyarrhythmia (p less than 0.05). Long-term encainide therapy was continued in 48 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Use of nonsustained ventricular tachycardia as a guide to antiarrhythmic drug therapy in patients with malignant ventricular arrhythmia.

From a population of 260 patients with malignant ventricular arrhythmia (ventricular fibrillation or ventricular tachycardia with syncope) we identified 52 (20%) who had infrequent ventricular premature beats during exercise testing and 48 hours of ambulatory monitoring. These patients underwent invasive electrophysiologic study utilizing programmed premature stimulation with up to three extrastimuli at currents of twice and three times middiastolic threshold. The end point for testing was nonsustained ventricular tachycardia (NSVT), defined as 3 to 20 propagated responses resulting from the last premature stimulus. A multiple response was obtained in 45 patients consisting of reproducible NSVT in 36 and sustained ventricular tachycardia in nine. The 36 patients with NSVT underwent 540 electrophysiologic tests with 18 antiarrhythmic agents. Suppression of the repetitive response was achieved in 31 of the 36 patients (86.1%). After an average follow-up of 21 months, one of 31 patients in whom the repetitive response had been abolished had recurrent arrhythmia. This contrasted with recurrence in two of the five patients in whom NSVT was still provoked. During the extensive testing, ventricular fibrillation was not induced. Sustained ventricular tachycardia occurred in 27 of the 540 tests (5.0%), but cardioversion was required in only 12 (2.2%). We conclude that NSVT constitutes a safe electrophysiologic end point for selecting an effective antiarrhythmic program in patients who have experienced malignant ventricular arrhythmia but in whom monitoring and exercise testing are inadequate to guide therapy.

Adolescent↗
PubMed1978

Cardiovascular effects of tricyclic and tetracyclic antidepressants.

Cardiovascular effects of therapeutic doses of tricyclic or tetracyclic antidepressants (TCA) were examined in 66 patients. After three weeks of therapy, heart rate and PR interval were increased (P less than .02, P less than .05), while prolongation of the QTc time and the QRS interval did not reach significant levels. We observed significant flattening of T waves (P less than .05), which was not associated with changes in the serum potassium level. These changes were reversible after treatment was discontinued. When therapy was maintained for 13 months, only the heart rate continued to be increased, whereas all other ECG values had returned to normal. The TCA therapy led to a significant prolongation of the preejection period (P less than .01) and slight shortening of the left ventricular ejection time, indicating a decrease in myocardial contractility. There was no difference of effects on the values studied between tricyclic and tetracyclic antidepressants.

Adult↗
PubMed1977

Anti-arrhythmic properties of acebutolol (Bay c 7705), a new cardioselective beta-adrenergic blocking agent: a preliminary report.

A study was carried out in 20 ambulatory patients with various heart diseases and different forms of cardiac arrhythmias to evaluate the anti-arrhythmic effect of acebutolol when given orally(400 mg/day). Long-term(4 hour) ECGs were monitored before and after 3 days of treatment. The results showed that after acebutolol treatment 60% of all the arrhythmias were prevented or abolised, 16% were improved, and only 24% persisted unchanged.

Acebutolol↗
PubMed1977

What does the symptom "palpitation" mean? - Correlation between symptoms and the presence of cardiac arrhythmias in the ambulatory Ecg.

The correlation between palpitations and arrhythmias was examined using 319 long term Ecgs of 167 patients. Furthermore, we attempted to determine the shortest possible recording time permitting the correct diagnosis of an arrhythmia and ST-segment changes. 31 arrhythmias (9.7%) were correctly identified by our patients; On the other hand, while there were 20 palpitations (39%) that could not be related to an arrhythmia we recorded 39 instances in which these same patients missed an arrhythmia. Tachycardias and multiple ventricular extrasystoles were most likely identified. Most of the rhythm disturbances (89%) appeared during the first 12 hours and all of the ST-segment changes eventually seen (100%) occurred until the end of 8 hours of recording. This study shows that ths symptom "palpitation" is a poor indicator of underlying rhythm disturbances. In the documentation of arrhythmias and/or ischemic ST-segment changes 8 to 12 hours of recording should usually be sufficient.

Arrhythmias, Cardiac↗
PubMed1976

[The systolic time intervals in functional disorders of the thyroid: a simple and fast screening test].

The systolic time intervals (LVET, PEP, and ratio LVET/PEP) were determined in 53 patients presenting with signs or symptoms of thyroid dysfunction. Patients with clinical evidence of congestive heart failure, with arterial hypertension or old myocardial infarction, and patients receiving cardioactive drugs, were excluded from the study. Thyroid function was evaluated by means of T3-RIA, serum thyroxin and TRH stimulation test.

Adult↗