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Biomedical subjects

H Drexler

Publications and source records attributed to H Drexler.

At least 217 records · Page 12Linked to original sources
PubMed1988

Transcription stimulates recombination. II. Generalized transduction of Escherichia coli by phages T1 and T4.

Phage Mu was inserted in the trpE gene of one donor Escherichia coli strain and in the lac promoter of another. Strains with Mu prophage mutations which permitted transcription of genes whose transcription had been polarly blocked by the Mu insertion were isolated and called "bypass" strains. The transducing phages T1am, and T1am,ST, and, in one instance, T4GT7 were grown on both the bypass and the original strains. After growth on the bypass strains transducing phages were able to transduce Trp+ and Lac+, respectively, to a variety of Trp- and Lac- strains more efficiently than after growth on nonbypass strains. These results support the idea that crossovers required for generalized transduction occur more efficiently if the specific region is transcribed by both interacting parental molecules.

Bacteriophages↗
PubMed1988

[Significance of atrial natriuretic peptide in heart failure: experimental findings].

We investigated the role of atrial natriuretic peptide (ANP) in a rat model of chronic heart failure (CHF) (coronary ligation) by four different studies: (1) stimulation of secretion of ANP by volume loading, (2) infusion of 1 micrograms/min of rat ANP (99-126), (3) correlations of pressure measurements of right atrium (RAP) and LVEDP versus plasma ANP levels and ANP mRNS versus infarct size, (4) blocking endogenous plasma levels of ANP with monoclonal ANP antibody. In severe CHF, volume loading did not exert a significant increase in plasma ANP, in contrast to moderate CHF or to normal animals. Infusion of ANP reduced RAP and LVEDP without significant increase in renal blood flow (radioactive microspheres) in rats with severe cardiac failure, in contrast to normal animals. A close relationship was found between LVEDP and atrial plasma levels. After injection of ANP antibody, filling pressures and systemic vascular resistance increased, indicating that removal of ANP may enhance arterial vasoconstriction or elevated endogenous ANP to exert a vasodilatory action in severe heart failure. Nevertheless, the cardiocirculatory effects, primarily on renal blood flow, appear to be limited.

Animals↗
PubMed1988

Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation.

Three cases of idiopathic myelofibrosis were screened for the presence of mutations at codon 12, 13, or 61 of the ras gene family by a rapid method based on polymerase chain reaction and hybridization to mutation-specific oligonucleotides. PB cells of one patient showed a point mutation at codon 12 of the N-ras oncogene. This molecular genetic hallmark was used to investigate the clonal relationship of different cell lineages by cell separation analysis. Presence of the N-ras 12 mutation in granulocytes, monocytes, B cells, and T lymphocytes, as well as erythroblasts, indicates that idiopathic myelofibrosis originates from a pluripotent stem cell, at least in this patient.

Clone Cells↗
PubMed1988

[Therapy of heart failure with vasodilator agents].

Vasodilation in congestive heart failure is an established therapeutic principal. The ventricular unloading improves contractile geometry and thereby improves working conditions for the contractile element: myocardial oxygen consumption falls and myocardial efficiency improves. This effect is independent from the vasodilating substance employed; it is, however, dependent on the simultaneous induction of pre- and afterload reduction. Vasodilation improves regional perfusion. Differential improvement in organ bloodflow is related to the type of vasodilator employed. It seems essential for a therapeutic benefit that renal and coronary perfusion are improved and that shunt flow, especially with steal phenomena, is avoided. Skeletal muscle bloodflow improves only slowly under ACE-inhibitor therapy. It could be shown that the immediate vasodilation due to ACE inhibition is followed by a second phase of vasodilation, which may be related to the influence of ACE inhibition of intraarterial wall angiotensin converting enzyme. Another factor possibly responsible for the delayed response to vasodilation in congestive heart failure, may be functional and structural changes in skeletal muscle. Reversal of these changes requires time. Both factors - the vessel wall related mechanism, as well as changes in parenchymal structure and function - require prolonged periods of treatment until therapeutic benefit can be seen.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Therapeutic advances in heart failure.

Annual mortality from congestive heart failure ranges from 15% to 60%, depending on the severity of the left ventricular damage and underlying disease. Most controlled trials have been too small to detect any beneficial effect on survival from the newer vasodilator and inotropic drugs. However, the results of two recent studies strongly suggest that some vasodilator drugs improve prognosis. In one study, a hydralazine-nitrate combination reduced 2-year mortality by 34%, while in another study, enalapril, in addition to diuretics, digitalis, and directly acting vasodilators, reduced 1-year mortality by 31%. Thus far no large studies have been published with the new phosphodiesterase-inhibiting agents. Although preliminary reports of large-scale trials did not demonstrate changes in survival rate, they have been shown to improve well-being in class III-IV congestive heart failure patients.

Heart Failure↗
PubMed1987

[Hemodynamic effect of intravenous diltiazem and nifedipine in acute myocardial infarct. A randomized study].

In a prospective, randomized trial of 28 patients with acute myocardial infarction nifedipine or diltiazem were administered intravenously and hemodynamic parameters and drug plasma levels measured for 24 hours. Both drugs lowered arterial blood pressure and peripheral resistance. Only diltiazem reduced heart rate and the heart rate x arterial pressure product, as pointer to a reduction in myocardial oxygen consumption. On the other hand, nifedipine is more likely to cause a (reflex) increase in heart rate. In no patient was there evidence of drug-induced hemodynamic impairment. Left ventricular filling pressure was reduced in those patients in whom it had been elevated. While a steady-state plasma concentration was quickly reached with nifedipine, in some patients diltiazem infusion produced a continuous rise in plasma concentration and, in two patients with posterior-wall infarction, high-grade a-v block (reversible after discontinuation of the drug). The results indicate that under ECG control both drugs can be used intravenously without much risk. The hemodynamic profile of diltiazem (reduction in peripheral resistance and heart rate) would seem to be particularly favorable in acute infarction, while nifedipine is preferred in acute infarction plus hypertension. The possible effect on a-v conduction is to be watched on intravenous administration of diltiazem, while in normotensive patients nifedipine may cause an undesirable (reflex-mediated) sympathetic activation.

Adult↗
PubMed1987

Polyclonal activation of human peripheral blood lymphocytes by bacterial porins and defined porin fragments.

Bacterial porins were isolated from Escherichia coli B and Salmonella typhimurium S 1135. The proteins were cleaved either by cyanogen bromide treatment or by enzymatic digestion into a variety of small fragments, and the compounds were characterized by SDS-polyacrylamide gel electrophoresis. Both the porins and the porin fragments constituted potent mitogens for human peripheral blood lymphocytes, comparable to the human B-lymphocyte activator pokeweed mitogen. In the cultures, B-lymphocytes were stimulated into immunoglobulin production, as measured by ELISA. In all experiments, the activity of the mitogens extracted from S. typhimurium was superior to that of the compound isolated from E. coli B. The well-defined porins constitute valuable tools for investigating the molecular mechanism of human lymphocyte activation.

Bacterial Outer Membrane Proteins↗
PubMed1987

Central and regional vascular hemodynamics following intravenous milrinone in the conscious rat: comparison with dobutamine.

This study examined the hemodynamic and regional vascular profile of intravenous (i.v.) milrinone during increasing doses (3, 6, 12 micrograms/kg/min, n = 8) and by intraindividual comparison of milrinone and dobutamine (n = 10) in normal conscious rats. At 3 micrograms/kg/min, Milrinone increased coronary and cerebral blood flow (radioactive microspheres 15 +/- 5 microns) (7.7-9.8 and 1.05-1.27 ml/min/g respectively, both p less than 0.05) without significant changes in systemic hemodynamics. At 6 micrograms/kg/min milrinone increased skeletal muscle blood flow (0.19-0.24 ml/min/g, p less than 0.05) along with increases in cardiac output, stroke volume, and stroke work (all p less than 0.05), while systemic vascular resistance decreased (-51%, p less than 0.05). When compared with dobutamine, milrinone caused a greater increase in cardiac output (+26% vs. +17%) and a greater reduction in systemic vascular resistance. Milrinone and dobutamine increased renal, intestinal, cerebral, and coronary flow to a similar extent, but only milrinone enhanced hepatic arterial blood flow (+26%, p less than 0.05) and tended to increase flow to skeletal muscle (+35%, p = 0.07). We conclude that milrinone exerts significant regional vasodilating effects in a conscious rat model, being most prominent in the coronary and cerebral circulations at a dosage that does not alter central hemodynamics. At higher doses, milrinone causes a balanced increase in regional blood flow including enhanced flow to skeletal muscle. The hemodynamic (particularly as compared with dobutamine) and regional vascular profile of milrinone suggests a predominant vasodilating effect in the rat. Given a similar limited response of rat and diseased human myocardium to milrinone, these findings may have important clinical implications.

Animals↗
PubMed1987

Blood flow distribution within skeletal muscle during exercise in the presence of chronic heart failure: effect of milrinone.

Recent studies suggest that, in the presence of heart failure, the capability of skeletal muscle to utilize delivered flow may be impaired due to maldistribution of blood flow within working muscle. Similarly, this mechanism could explain the failure of drugs to improve maximal oxygen consumption (VO2max) immediately. Accordingly, we assessed muscular blood flow distribution (ml/min/g, radioactive microspheres, 15 +/- 5 micron) among and within working muscle, VO2max, and arterial lactate in a rat preparation of myocardial infarction and heart failure (infarct size 36.0 +/- 3.3% of the left ventricle, n = 9), and in sham-operated animals (n = 11). Data were obtained at maximal treadmill exercise during alternate infusions of milrinone and saline. Total skeletal muscle blood flow during exercise was significantly lower in the infarction group (p less than .05 vs sham); reduced blood flow was primarily attributed to decreased flow to oxidative working muscle such as soleus and the red portion of gastrocnemius, whereas blood flow to glycolytic muscle portions (e.g., gastrocnemius white, vastus lateralis white) was similar in the infarction and sham-operated groups. Milrinone increased flow to the glycolytic working muscle portions in sham-operated animals (e.g., vastus lateralis white, 0.23 vs 0.29, p less than .05); by contrast, blood flow to the oxidative muscle fibers was increased in the infarction group (e.g., gastrocnemius red, 1.45 vs 1.87, p less than .05). Arterial lactate levels at similar workloads during exercise were higher in the infarction group (p less than .05). Neither lactate nor VO2max were significantly altered with milrinone in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Facilitation of ECT by caffeine pretreatment.

In this study, eight patients participated in a standardized protocol to assess the effects of caffeine on seizures in ECT. Caffeine sodium benzoate (500-2000 mg) was administered intravenously 10 minutes before ECT, and seizure duration was compared with that of a previous treatment unmodified by caffeine. Seizure duration was significantly increased during ECTs preceded by caffeine. Three other patients given caffeine when seizures of adequate duration could no longer be elicited at maximal stimulus levels experienced longer seizures. Administration of caffeine was not associated with significant cardiovascular or other (including cognitive) adverse effects.

Benzoates↗
PubMed1987

Early clinical evaluation of the intravenous treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activator complex.

50 consecutive patients with acute myocardial infarction and symptoms of less than 4 hours duration were treated with anisoylated plasminogen streptokinase activator complex (APSAC) 30U intravenously as a bolus injection over 5 minutes. An open infarct-related artery was found in 32 patients (64%) when the first coronary angiography was taken 66 +/- 21 minutes after APSAC. Complete reperfusion was subsequently seen in 10 of 18 patients with an occluded infarct-related artery 74 +/- 16 minutes after injection of APSAC. Thus, a patient infarct-related artery was seen in 42 patients (84%) within 68 +/- 20 minutes. A control coronary angiography was performed in 37 patients (74%) after 25 +/- 19 days. Reocclusion was found in 5 patients. The minimal cross-sectional area of the residual coronary stenosis increased from 1.3 +/- 0.9 mm2 to 1.8 +/- 1.9 mm2. Patients with residual thrombi after coronary thrombolysis (n = 13) demonstrated an increase of the minimal cross-sectional area of the residual stenosis from 1.2 +/- 0.8 to 2.6 +/- 2.3 mm2, whereas those without residual thrombi showed only minor changes of the minimal cross-sectional area (1.3 +/- 0.9 to 1.2 +/- 1.2 mm2). Thus, APSAC demonstrated a high patency rate and a low reocclusion rate after intravenous administration. The prolonged fibrinolytic activity of APSAC leads to a further regression of the residual coronary stenosis among patients with coronary thrombi after reperfusion.

Adult↗
PubMed1987

[Central and regional vascular hemodynamics of milrinone in experimental heart failure: comparison with captopril and dobutamine].

The present study was designed to evaluate the regional vascular profile of milrinone in the setting of experimental heart failure. Utilizing the rat model of myocardial infarction and failure (average infarct size 28%), we measured cardiac output (CO), arterial pressure (MAP), LVEDP, heart rate and systemic vascular resistance, as well as regional blood flow (radioactive microspheres 15 +/- 5 microns) before and after milrinone i.v. (20 microns/kg bolus, 3 micrograms/kg/min infusion) in the conscious state (LVEDP 22 mm Hg versus 10 mm Hg in the sham-operated group, p less than 0.01). Similarly, central hemodynamics and regional blood flow were determined before and after dobutamine or captopril, administering equipotent doses. Milrinone reduced LVEDP more than dobutamine, both more than captopril; MAP was decreased by captopril only. Although all three drugs reduced SVR to a similar extent and increased CO, a quite different blood flow distribution occurred. Improvement in flow to skeletal muscle and splanchnic circulatory bed was exerted by milrinone only. Thus, milrinone attenuated the vasoconstriction in those circulations known to be impaired in heart failure. In contrast to captopril, the effects of milrinone on renal perfusion were modest. These results demonstrate the potent vasodilator activity of milrinone, which is independent of its direct-positive inotropic effects, being most prominent in the splanchnic, coronary and skeletal muscle circulation. The latter might have clinical relevance since improved muscular flow during exercise is likely to improve exercise capacity in heart failure after long-term treatment.

Animals↗
PubMed1987

Acute regional vascular effects of intravenous captopril in a rat model of myocardial infarction and failure.

The effects of i.v. captopril on regional blood flow (radioactive microspheres, 15 +/- 5 micron), hemodynamics and maximal oxygen consumption were evaluated in conscious rats with congestive heart failure due to large myocardial infarction (n = 9, infarct size 39.5 +/- 2% of left ventricle) and compared to data obtained from rats subjected to sham surgical procedures (n = 8). In both groups data were obtained at rest and during submaximal treadmill exercise during alternate infusion of captopril and saline. In the congestive heart failure group captopril reduced systemic vascular resistance, mean arterial pressure and left ventricular systolic pressure (P less than .05 each). Blood flow to the renal, gastrointestinal and coronary circulations was reduced in the heart failure group treated with saline vehicle. Flow to the renal and gastrointestinal beds of heart failure animals was enhanced to values similar to those observed in sham animals during captopril treatment. Left ventricular coronary flow was also increased significantly by captopril in both sham and heart failure animals. The most prominent effects of captopril occurred in the renal circulation of the heart failure group in which blood flow increased by 55%. Blood flow to skeletal muscle and skin was unchanged by captopril both in sham and heart failure animals at rest and during exercise. Maximal oxygen consumption was not affected by captopril treatment. Thus, captopril induced a differential pattern of vasodilation with the greatest effect in the renal bed and a less intensive effect in the gastrointestinal and coronary beds. The unchanged flow to skeletal muscle may explain the failure of captopril to improve exercise capacity after short-term administration.

Animals↗
PubMed1986

[Calcium antagonists in heart failure?].

Although beneficial acute hemodynamic effects of calcium antagonists in heart failure have been reported, their use in this setting is still controversial because of the negative inotropic effects produced by these agents. The direct actions of calcium antagonists, that is direct depression of myocardial contractility and coronary and peripheral vasodilation, are modulated by systemic hypotension-induced baroreceptor activation of autonomic reflexes. Thus, at clinically relevant dosages, the baroreceptor-mediated cardiac stimulatory effects may counterbalance or override the direct negative-inotropic effects, as usually observed with nifedipine or diltiazem. By contrast, with verapamil significant depression of contractility may occur. Newer calcium antagonists with higher vasoselectivity such as nisoldipine or felodipine may be particularly interesting in the setting of congestive heart failure because of pronounced arterial vasodilatation and their additional effects on coronary blood flow, LV-regional wall motion and diastolic function and peripheral blood flow distribution with negligible myocardial effects. Due to their marked vasodilatating properties, newer derivatives may be advantageous in the treatment of heart failure due to coronary artery disease and hypertension. Although limited data concerning long-term efficacy are available, preliminary studies suggest long-term benefit in selected patients. It appears that verapamil should not be used for vasodilator therapy of severe heart failure, since deterioration of LV function may occur.

Calcium Channel Blockers↗