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Biomedical subjects

R Engler

Publications and source records attributed to R Engler.

At least 37 records · Page 2Linked to original sources
PubMed1988

Late clinical outcome in patients with early ventricular fibrillation after myocardial infarction.

Whether ventricular fibrillation occurring within 48 h after acute myocardial infarction is associated with particular clinical features and poor prognosis, especially in patients with anterior myocardial infarction, is still debated. Therefore, clinical variables and in-hospital and 1 year mortality rates were analyzed in 2,088 patients, aged 18 to 95 years (mean +/- SD 64 +/- 12), admitted to the hospital with acute myocardial infarction between 1979 and mid 1984. One hundred forty-seven patients (7%) had at least one episode of ventricular fibrillation occurring within 48 h of hospital admission. Of these, 25% died during their initial hospitalization compared with 13% of patients without early ventricular fibrillation (p less than 0.001). In greater than 50% of patients with early ventricular fibrillation, the immediate cause of death was left ventricular failure or cardiogenic shock. In contrast, the 1 year mortality rate after hospital discharge was not significantly greater in patients with than in those without early ventricular fibrillation (15 versus 11%, respectively), particularly in the subgroup of patients with anterior myocardial infarction in which the mortality rate tended to be lower in patients with early ventricular fibrillation (8 versus 14%, respectively). Similar mortality results were found when only primary (not associated with left ventricular failure) ventricular fibrillation was analyzed. The left ventricular ejection fraction and the incidence of complex ventricular arrhythmias from 24 h ambulatory electrocardiographic monitoring obtained at hospital discharge were not different in survivors with or without early ventricular fibrillation (0.45 +/- 0.13 versus 0.49 +/- 0.14 and 41 versus 41%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Glycosylation of chicken haptoglobin: isolation and characterization of three molecular variants and studies of their distribution in hen plasma before and after turpentine-induced inflammation.

Chicken haptoglobin (Hp), a hemoglobin-binding protein isolated from chicken plasma, is composed of three molecular variants that react differently with concanavalin A (ConA). These glycosylation variants of chicken Hp have been isolated by affinity chromatography using Sepharose-bound ConA. They differ in their molecular weight, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Analysis of the glycopeptides obtained after pronase digestion of these variants yielded two types of structures: one, reactive with ConA, corresponded to a biantennary N-linked carbohydrate unit and one, unreactive with ConA, corresponded to a triantennary unit. The strongly ConA-reactive Hp variant bears only two biantennary units and the nonreactive Hp variant bears only two triantennary units; the weakly reactive Hp variant bears equal amounts of both units. The distribution of Hp glycosylation variant does not show any significant difference when obtained from the plasma of laying hens before and after turpentine-induced inflammation.

Animals↗
PubMed1988

[Proteins of the inflammatory reaction. Regulatory functions].

There is a very important modification of the plasma protein equilibrium during an inflammatory reaction. Most of the proteins, except the immunoglobulins, have their biosynthesis or catabolic rate modified. The plasma concentration of these proteins may be increased, decreased or equal to the normal values. Clinically, the term "Acute Phase Protein" APP is reserved for the proteins whose plasma concentration is at least 50 per cent higher than normal values. These APP are: alpha-1 acid-glycoprotein, alpha-1 proteinase inhibitor, alpha-1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A protein. Interleukin-1 induces the APP's hepatic biosynthesis. The APP and, more generally, a lot of plasma proteins play a role during inflammatory reaction. They have some real functions of metabolic regulators. The functions result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The interaction of plasma proteins and particularly the APP's with different ligands issued from the inflammatory site, is an example of physiopathological self regulation.

Acute-Phase Proteins↗
PubMed1988

Purification and characterization of two different precursor forms of the cathepsin B-like proteinase from human malignant ascitic fluid.

We have purified two different precursors of a cathepsin B-like proteinase (PCBT) from malignant ascitic fluid. The molecular mass of these proteins were 45-47 kDa and 36 kDa, respectively. This report is the first which shows cathepsin-B precursors as purified proteins. By using sheep immunoglobulins directed against denatured lysosomal cathepsin B, we have found that both precursors, together with the 33-kDa pepsin generated cathepsin B-like proteinase, reacted in immunoblotting: the three components are thus cathepsin B-related. These antibodies allow us the show that during pepsin activation the 45-47 kDa precursor is converted to the 33-kDa cathepsin B-like proteinase together with the 36-kDa PCBT. We have also prepared sheep immunoglobulins directed against the 36-kDa precursor. The generation of the cathepsin B-like proteinase by pepsin digestion of purified precursors followed a time and dose dependent process. This latter result argues for activation through peptide bond cleavages.

Ascitic Fluid↗
PubMed1988

Alpha-1-acid glycoprotein concentrations and protein binding of propranolol in Sprague-Dawley and Dark Agouti rat strains treated by phenobarbital.

Propranolol binding to rat serum samples was studied after 7 days of phenobarbital (PB) administration to induce alpha-1-acid glycoprotein (AAG). In male Sprague-Dawley rats, serum AAG concentrations and the bound/free propranolol ratio (B/F) were increased slightly after enzyme-inducing drug administration (mean +/- S.D.): from 0.30 +/- 0.04 to 0.49 +/- 0.05 g/l for AAG and from 6.79 +/- 1.24 to 8.81 to 1.31 for B/F. In male DA (Dark Agouti) rats, the same parameters increased greatly: from 0.20 +/- 0.01 to 1.38 +/- 0.13 g/l for AAF and from 8.75 +/- 1.01 to 27.15 +/- 3.28 for B/F. PB concentrations determined on the same serum samples were similar in both rat strains. Female DA rats also were responsive to PB administration. Propranolol binding to DA rat serum from the treated group was characterized by an increase in high-affinity binding site concentrations. The binding of propranolol to isolated rat AAG at various concentrations (0.2-1 g/l), alone or associated with rat serum albumin at a constant concentration (36 g/l), also was studied. Propranolol binding capacities to rat AAG were increased 2.4 times by the presence of albumin and consequently B/F values for both proteins agreed with values obtained with serum samples. These results indicate that increased propranolol binding to rat serum induced by PB administration is probably a direct consequence of increased concentrations of AAG. The high sensitivity of DA rats to PB suggests that this strain should be used preferentially for the study of the effect of cytochrome P-450 inducers on AAG metabolism and cationic drug binding.

Animals↗
PubMed1987

Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia.

During acute myocardial ischemia, granulocytes accumulate and obstruct the microcirculation. Granulocytes remain plugged in individual myocardial capillaries on reperfusion and are the major cause of the no-reflow phenomenon. During 3 h of ischemia, the granulocyte content of myocardium measured by 111In labeling increases from 1.0 X 10(6) to 1.5 X 10(6) cells/g, and after 5 min of reperfusion increases to 2.4 X 10(6) cells/g. The effects of granulocytes during 1 h of acute ischemia were determined by comparing agranulocytic to whole blood perfusion. With whole blood collateral flow decreased, water content increased (edema), ventricular fibrillation was common, and 27% of capillaries had no-reflow, whereas in the absence of granulocytes, collateral flow increased, there was no edema, arrhythmias were rare, and the no-reflow phenomenon was completely prevented. It is unfortunate that the inflammatory signals triggered by ischemia remain active on acute reperfusion, limit tissue salvage, and perhaps cause reperfusion injury. Several activating stimuli for granulocytes are known, but what inhibits them? Adenosine is known to inhibit superoxide radical formation by granulocytes, and 5-amino-4-imidazole carboxamide-riboside (AICA-riboside) augments adenosine release from energy-deprived cells. In dogs subjected to 1 h of ischemia, AICA-riboside pretreatment augmented adenosine release by nearly 10-fold, which was accompanied by a significant increase in collateral blood flow and decreased arrhythmias. We propose a new hypothesis: adenosine acts as a natural antiinflammatory autacoid during transient injury linking the ability to catabolize ATP (an indicator of viability) to granulocyte inhibition, thus preventing premature activation of the inflammatory response to cell death. Granulocytes are active participants in acute myocardial ischemia and means to prevent their activation, remove them from the reperfusate, or inhibit them will be necessary for optimum reperfusion salvage.

Adenosine↗
PubMed1987

Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.

Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.

Agranulocytosis↗
PubMed1986

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

Adrenergic beta-Antagonists↗
PubMed1986

Inhibition of the cathepsin B like proteinase by a low molecular weight cysteine-proteinase inhibitor from ascitic fluid and plasma alpha 2 macroglobulin.

The cathepsin B like proteinase present in ascitic fluid of a patient with neoplasia has been purified and characterized after pepsin activation. From this fluid we have prepared the low molecular weight (LMW) cysteine-proteinase inhibitors. Three major inhibitor forms were found with isoelectric points of 7.4, 5.4, and 5.1, respectively. The interaction of the enzyme with the former inhibitor was studied because this inhibitor was the most abundant. The Ki value was found to be 4.3 X 10(-8) M. Two molecules of this proteinase were bound by one molecule of plasma alpha 2 macroglobulin (alpha 2M). The LMW inhibitor was able to bind to the enzyme entrapped in alpha 2M and reduced its endopeptidase activity on benzyloxycarbonyl-L-phenylalanyl-L-arginine-4-methyl-7-coumarylamide. These results may have a physiological significance in the regulation of the enzyme which, among other extracellular hydrolases, probably plays an important role in tumor invasion.

Ascites↗
PubMed1985

Malaria, cause of ahaptoglobinaemia in Africans.

The lack of serum haptoglobin in Africans has been investigated in the Congo, Central Africa, where HpO prevalence is about 30%. This study shows that it is possible to suppress ahaptoglobinaemia within a few weeks by antimalarial chemoprophylaxis, that it does not occur in protected individuals, that ahaptoglobinaemia reappears at its original incidence levels after interruption of chemoprophylaxis, and that some individuals are more susceptible in relation to Hp2 gene. Malaria is the only significant cause of ahaptoglobinaemia in subjects both with and without detectable parasitaemia. The possible mechanisms involved are discussed.

Amodiaquine↗
PubMed1985

[Regulation of neoplasm-specific cathepsin B by cysteine-protease inhibitors present in cancerous exudates].

The Cathepsin B-like proteinase, a secretory form of lysosomal cathepsin B, is present in some cancerous exudates (i.e. pleural and ascitic fluids). It has been suggested that this enzyme may be involved in the invasive process, one of the most important aspects of cancer pathology. In the same fluids, two kinds of cysteine-proteinase inhibitors (C.P.I.'s) are found- HMr-CPI (90,000 daltons) and LMr-CPI's (11,000-13,000 daltons). The Cathepsin B-like enzyme is more strongly inhibited by the LMr-CPI's than by the HMr-CPI, the Ki values are 4.0 X 10(-9) M and 1.2 X 10(-7) M respectively. Theses results underline the similarity between this enzyme and the lysosomal Cathepsin B. On the other hand, the inhibitors could play a protective role against tumor invasion.

Ascitic Fluid↗
PubMed1979

Is immunochemical determination of haptoglobin phenotype dependent?

Immunochemical methods have been used to determine the concentration of haptoglobins. The dependence on the phenotype was tested with highly purified Hp 2-1, Hp 2-2 and Hp 1-1, by immunonephelometry and radial immunodiffusion (RID). Measurements with three different instruments: automated immunonephelometer (AIP, Technicon), laser nephelometer (LN, Behring) and immunochemistry system (ICS, Beckman) were performed. For each type of apparatus antisera against a pool of haptoglobins were provided by the respective manufacturers. Some experiments were done with an antiserum to the haptoglobin heavy chain prepared in the laboratory. This study shows that haptoglobin determination depends neither on the physical geometry of the instruments or on the type of antiserum used in this work. In contrast, the data display a dependence on haptoglobin phenotype. When Hp 2-1, the most common phenotype, is taken as a standard, thd values obtained for Hp 2-2 are in good agreement with those obtained for Hp 2-1. However, the values obtained for Hp 1-1 are overestimated unless they are corrected by an experimental factor which has been determined in this study.

Haptoglobins↗
PubMed1979

Efficacy of a new oral agent (tocainide) in the acute treatment of refractory ventricular arrhythmias.

To assess the efficacy of tocainide, a new oral analog of lidocaine, 30 patients with ventricular arrhythmias refractory to quinidine, procainamide and propranolol were treated with this agent. The dose of tocainide ranged from 400 to 800 mg every 8 hours. Peak tocainide blood levels 1 to 4 hours after administration ranged from 5.0 to 15.0 microgram/ml (mean 10.3). The suppression of ventricular premature beats by 75 percent or more was arbitrarily used as a measure of drug efficacy. In 13 patients who met this criterion, ventricular premature complexes, assessed with 24 hour ambulatory tape monitoring, decreased by an average of 88 percent. In 8 of 11 patients, repeated symptomatic bouts of ventricular tachycardia were completely suppressed. Considering both the response of ventricular premature complexes and the abolition of ventricular tachycardia, 18 patients (60 percent) responded to tocainide. Twenty-one patients (70 percent) had initial gastrointestinal and central nervous system side effects; most of these were transient or responded to a reduction in dose. In two patients disorientation and a skin rash required withdrawal of tocainide. These adverse effects did not appear to be due to the interaction of tocainide with other antiarrhythmic agents. It is concluded that tocainide is an effective oral agent for the therapy of potentially lethal ventricular arrhythmias refractory to other medication.

Administration, Oral↗