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Biomedical subjects

S Braun

Publications and source records attributed to S Braun.

At least 19 recordsLinked to original sources

Specific effect of corticoids on acetylcholine receptor expression in rat skeletal muscle cell cultures.

The potential effect of different classes of steroids on the expression of acetylcholine receptors (AChR) was studied in different primary cultures of newborn-rat skeletal muscle cells. Comparison among three techniques for preparing newborn skeletal muscle cells showed that these systems were equivalent to study AChR expression. Only corticoids stimulated myogenesis as a twofold increase in AChR expression indicated. Among the corticoids, the glucocorticoids were the more potent, whereas the mineralocorticoid aldosterone had less marked effect. The sex hormones progesterone and testosterone partially blocked these effects, without inducing any significant effect when given alone. The steroids tested differed in efficacy in correlation with their different chemical structures. Among the glucocorticoids a clear structure-activity relationship could be established. These results emphasize the specificity of corticoid action on muscle cells and suggest an explanation for the effects induced by glucocorticoids used in treating human muscular or neuromuscular diseases.

Adrenal Cortex Hormones

Fetal presentation of Morquio disease type A.

A fetus with mucopolysaccharidosis type IV A (Morquio type A) is described. The family had one affected child exhibiting symptoms of classical Morquio A disease, and late in the subsequent pregnancy prenatal diagnosis was requested. At 23 weeks' gestation, moderate ascites was detected by detailed ultrasound scan and keratan sulphate was found in the amniotic fluid. The pregnancy was terminated by prostaglandin induction and the diagnosis of mucopolysaccharidosis type IV A was confirmed by demonstration of a deficiency of N-acetylgalactosamine-6-sulphate (GalNac-6-S) sulphatase in cultured amniotic cells and in post-mortem fibroblast cultures. The activities of beta-galactosidase and arylsulphatase A were normal, ruling out Morquio disease type B and multiple sulphatase deficiency. These results indicate that mucopolysaccharidosis IV A (a disease that predominantly affects the skeletal system) may produce ascites in the fetus to such an extent that it can be detected by ultrasound.

Amniocentesis

Potentiation of cardiodepressive action among calcium antagonists from different classes: evidence for a mechanism at the single calcium channel level.

The ability of calcium antagonists and antiarrhythmic agents to potentiate the negative inotropic effects of calcium antagonists was investigated in guinea-pig left atria. The potency of nitrendipine was enhanced by several amphiphilic agents by one order of magnitude or more (by pretreatment with quinidine or bepridil). The effect of preincubation with bepridil was investigated for a larger number of dihydropyridines. Only some of them were potentiated like nitrendipine. There was no potentiation between any two members of the same chemical group, i.e. between two dihydropyridines or two catamphiphilic calcium antagonists. The interaction between bepridil and nitrendipine was studied in more detail. In atria, its extent was influenced by several conditions, such as the stimulus frequency, the incubation temperature, or the extracellular K+ concentration. In measurements of whole-cell calcium currents in guinea-pig myocytes, the interaction was found to take place in a quantitatively similar manner. At the single channel level, an enhancement of the effects could also be demonstrated. It appears here that both drugs interact by binding to the same channel molecule. We conclude that the interaction may be due to 1.: an amphiphilic drug (like bepridil) binding to the channel very transiently and thus briefly favouring the inactivated channel state, which means that 2.: the other drug (like nitrendipine) has a higher chance to be bound because of its high affinity towards inactivated channels. Alternative explanations are also discussed.

Animals

Risk factors for systemic embolism in patients with paroxysmal atrial fibrillation.

The purpose of this study was to define the risk factors for systemic embolism in patients with recently diagnosed paroxysmal atrial fibrillation. We therefore studied 63 consecutive patients with symptomatic nonvalvular paroxysmal atrial fibrillation and performed a clinical and noninvasive cardiac, peripheral vascular, and neurologic evaluation that included two-dimensional echocardiography, 24-hour Holter monitoring, and computed tomographic brain scan. Patients with predisposing clinical conditions for systemic embolism (valvular heart or coronary artery disease) or paroxysmal atrial fibrillation (sick sinus disease, preexcitation, or thyroid dysfunction) were excluded. At entry 34 patients had idiopathic paroxysmal atrial fibrillation and 29 had hypertension. Fourteen patients had a recent systemic embolic complication: nine had a recent occlusive nonlacunar cerebrovascular accident, two had transient ischemic attacks, and three had peripheral systemic emboli that required surgery. In addition, five patients had evidence of old cerebrovascular accident on the computed tomographic scan (group 1). Forty-four patients had no systemic embolism (group 2). Results of univariate analysis showed that patients in group 1 were older (72 +/- 9 vs 63 +/- 13 years, p less than 0.05), had a higher incidence of hypertension (70% vs 35%, p less than 0.01), and had an increased left atrial diameter (4.1 +/- 0.7 vs 3.6 +/- 0.5 cm, p less than 0.05). Multiple stepwise logistic regression analysis showed that a history of hypertension and left atrial enlargement on two-dimensional echocardiography were significant independent risk factors for systemic embolism in patients with symptomatic nonvalvular paroxysmal atrial fibrillation.

Aged

Different degradation rates of junctional and extrajunctional acetylcholine receptors of human muscle cultured in monolayer and innervated by fetal rat spinal cord neurons.

It is well demonstrated that in intact animals the degradation rate of the junctional acetylcholine receptor (AChR) is significantly slower than that of the extrajunctional receptor. Such data, however, are not available for human AChRs because the required experimentation cannot be performed in humans. We have now studied the degradation rate of the junctional and extrajunctional AChRs, utilizing our tissue culture model, in which well-differentiated neuromuscular junctions (NMJs) form on human muscle cultured in monolayer and innervated long-term by fetal rat spinal cord neurons. Half-life of AChRs was studied by a method utilizing the autoradiography of 125I-alpha bungarotoxin and computerized video image analysis. Extrajunctional AChRs degraded with a half-life of 1.3 days whereas junctional AChRs degraded with a half-life of 3.5 days. Our studies demonstrate for the first time that in innervated cultured human muscle: (a) the life span of human junctional AChR, is approximately 3 times longer than that of the extrajunctional AChR and (b) the stability of human AChR is neuronally regulated. This system can now be applied to evaluate the influence of pharmacologic agents on the stability of human junctional AChR, which is of potential importance in the treatment of myasthenia gravis and other diseases of the NMJ.

Animals

Nikkomycin production in pellets of Streptomyces tendae.

In previous submerged fermentation experiments mycelial suspensions of Streptomyces tendae were viscous and availability of oxygen limited the yield of nikkomycins (Nk), a complex of secondary metabolites which includes nucleoside-peptides with antibiotic activity. Increasing agitation improved oxygen transfer but consumed considerable power and shear-damaged cells. In this paper, cellular aggregates (pellets) were used to reduce viscosity and protect cells from shear. Under the conditions tested, specific productivity of S. tendae pellets increased with increasing size up to 1.4 mm diameter and then decreased. The maximal specific productivity of S. tendae pellets (44 mg Nk/g dry weight/h) occurred at a very low cell concentration. Pellet formation or high biomass concentration was required for the production of bioactive dipeptide and tripeptide Nks. It is speculated that accumulation of intermediates in large pellets activates the production of mature secondary metabolites.

Aminoglycosides

[Dissection of the ascending aorta (type A): diagnostic aspects, surgical treatment and long-term follow-up].

Aortic replacement is the treatment of choice and improves the natural history of dissections involving the ascending aorta. Forty patients (23 male), aged 49.4 years, have been operated at the hospital Clínico de la Universidad Católica. Twenty six presented with acute dissections. Angiography conformed the dissection in 63.3% and computed axial tomography in 84.6% of patients; lately, transesophageal echocardiography has become the most sensitive diagnostic method. Twenty three patients (57.5%) were subjected to emergency operations and 17 to semielective procedures. In 24 patients (60%) ascending aorta was replaced and in 16 a composite graft was used. Operative mortality was 27.5%. Univariate analysis showed that the period in which the operation was performed and the presence of limb ischemia were the only independent predictors of operative mortality. Long term follow up was achieved in 26 patients (89.6%). Actuarial 5 year survival without considering operative mortality was 87.9%. It is concluded that patients with acute dissections involving the ascending aorta should be operated as soon as the imaging diagnosis is complete and, since this is a palliative procedure, a close follow up is required for early detection of complications.

Adult

[Risk of chronic oral anticoagulant treatment in elderly patients].

To assess age-related risks of long term anticoagulation, the records of 348 patients followed up at our university hospital outpatient anticoagulation clinic during a seven year period were reviewed. There were 129 patients, under 56 years of age, 144 from 56 to 69 and 75 over 70 years old. The total observation period was 1089 patient-years (3.3 yrs per pt). 64% of the patients had adequate anticoagulation level (prothrombin time < 35%, INR 2.2-4.5) 70 to 100% of the observation period. Prothrombin time was slightly, but significantly higher in the elderly group. During this period 21 patients developed major bleeding complications (1.84/100 pt yrs), 8 of them with fatal intracranial hemorrhages, and 20 embolic complications (1.93/100 pt yrs), 3 of them fatal. No significant differences in the incidence of both bleeding and embolic complications were observed in the three groups. The results of this retrospective follow-up study suggest that long term anticoagulation can be carried out in elderly pts with risk of hemorrhagic and embolic complications similar to those observed in the general population.

Acenocoumarol

Properties of trypsin and of acid phosphatase immobilized in sol-gel glass matrices.

Trypsin and acid phosphatase-containing silica sol-gel glasses were obtained by mixing a solution of an enzyme with polyethylene glycol (PEG) 6000 and tetramethoxy orthosilicate at room temperature, followed by gelation and drying. Activity of the immobilized trypsin toward small substrates, such as N-benzoyl-L-arginine-4-nitroanilide at its Km, for the best preparations equaled that of the soluble enzyme. Polylysine (M(r) less than or equal to 13,000) and aprotinin (M(r) = 6,500) inhibited this activity. Larger polylysines as well as soybean trypsin inhibitor (M(r) = 20,100) were ineffective. The sol-gel-entrapped trypsin activity was stable when sol-gel glasses were incubated at ambient temperature (pH 7.5) for several months. In comparison, trypsin, immobilized in sol-gel glass by surface adsorption and incubated under the same conditions overnight, was completely autodigested. The firm interaction between the protein molecules and the silica matrix stabilized the enzymes. Thus, the half-life of sol-gel-entrapped acid phosphatase at 70 degrees C (pH 8.0) was two orders of magnitude larger than that of the enzyme in solution. Transparent, mechanically and chemically stable bioactive sol-gel glasses may be used for the development of robust on-line biochemical photodetection sensors and for the purposes of chemical catalysis.

Acid Phosphatase

[Interventricular rupture following myocardial infarction. Surgical treatment and long-term follow-up].

The natural course of post myocardial infarction ventricular septal defect is towards cardiogenic shock and death. 50% in the first week, over 90% a year latter. Between 1973-1989, 28 patients where operated on. Before surgery 14 patients (53%) where in Killip IV, 5 patients (19%) in III, 5 patients (19%) in II and 2 patients in I. The repair was accomplished under hypothermia and cardioplegia, with the insertion of a Teflon patch to close the defect in 20 patients (70%). Complementary procedures (CABG, Pacemaker, repair of dissections) were performed in 12 patients (47%). Three patients (10%) could not be weaned from the pump; another 10 (36%) died before discharge: 2 with multisystem failure and sepsis, the other 8 with cardiogenic shock (4 with residual VSD). The only independent predictor of operative mortality, by univariate analysis, was preoperatory cardiogenic shock. All 15 survivors (100%) where followed between 5 months and 14.5 years (mean 104.5 months). Two patients died at 4 years, one at 10, another at 10.5 years. The actuarial probability of being alive after discharge was 100% at 4 years, 75% at 5, and 50% at 10 years. At last follow up only 2 patients had mild dyspnea, the remaining where asymptomatic. Surgical treatment provides an opportunity to improve this otherwise dismal survival and offers a surprising good long term result. An early diagnosis and efficient repair, before the onset of cardiogenic shock, should provide better results.

Actuarial Analysis

Hemodynamic changes in underweight pregnant women.

Twelve normal-weight and 12 underweight women were compared to test whether fetal growth retardation in underweight gravidas is related to inadequate maternal hemodynamic adjustments. Plasma volume (+/- standard error) was 3227 +/- 103 mL in normal-weight and 2731 +/- 84 mL in underweight women (P less than .002). Cardiac output was 6340 +/- 167 mL/minute in controls and 5689 +/- 213 mL/minute in underweight women (P less than .03). Total peripheral vascular resistance was lower in controls than in underweight subjects (1025 +/- 31 versus 1198 +/- 58 dyne/second/cm5). Mean birth weight was 2837 +/- 125 g in underweight women and 3362 +/- 106 g in controls (P less than .005). Similarly, placental weight was reduced in the underweight group. All infants delivered by control mothers had a normal birth weight, whereas six infants from underweight gravidas were growth-retarded. In all cases combined, maternal plasma volume correlated significantly with both birth weight (r = 0.6, P less than .002) and placental weight (r = 0.56, P less than .01); total peripheral vascular resistance also correlated significantly and inversely with newborn weight and placental weight. Cardiac output correlated only with placental weight (r = 0.54, P less than .02). These results are consistent with the hypothesis that underweight mothers are at higher risk of fetal growth retardation because of a smaller plasma volume and lower cardiac output.

Adolescent

[Tendinitis of the foot].

Tendinitis in the ankle and foot is frequent. It is due to overwork, relative senescence or rheumatoid inflammation. Damages are graded from isolated lesions of the sheath to rupture of the tendon. The diagnosis, at least anatomical, is facilitated by the superficiality of the tendons and by good anatomico-functional knowledge. Treatment rules cannot really be established. Surgery should remain wide open. The foot should always be the best static and dynamic conditions, and this can be achieved by possible plantar ortheses and by the quality of footwear.

Foot

[High spontaneous variability of ventricular arrhythmias limits the evidence gained by long-term ECG studies].

The spontaneous variability of ventricular arrhythmias was investigated in 8 patients with chronic coronary heart disease. In each patient 6 eight-hour long-term ambulatory ECG recordings were made. During the first three periods patients were without medication and during the following three periods they received a placebo b.i.d. Hour to hour variability was high in all patients. When compared with the first hour of an eight-hour period the number of ventricular premature beats (VPB) per hour in four patients declined by more than 90%, in two patients by more than 70% and in only two by less than 50%. On the other hand, increments of several hundred percent were often observed. Day to day variability of VPBs was also high. When compared with the first documented eight-hour period VPBs either decreased or increased substantially (-84% to +940%). A spontaneous reduction of VPB's for several hours may simulate an antiarrhythmic drug effect. For the group as a whole placebo had a significant effect on the number of VPBs (p less than 0.001). Beside variations of quantity, the complexity of ventricular arrhythmias (Lown classification) spontaneously changed several classes in one patient. Therefore, high spontaneous variability renders it very difficult to estimate the behaviour of ventricular arrhythmias in the individual patient with the Holter-ECG.

Arrhythmias, Cardiac

Adenosine receptor permanently coupled to turkey erythrocyte adenylate cyclase.

The mode of coupling of the adenosine receptor to adenylate cyclase in turkey erythrocyte membranes was probed by two independent approaches. The progressive inactivation of the adenosine receptor by an adenosine receptor affinity label resulted in the proportional reduction in the adenosine plus GppNHp dependent specific activity. In contrast, the intrinsic rate constant (k3), characterizing the process of adenylate cyclase activation by the adenosine-adenosine receptor complex, is independent of the extent of receptor inactivation. This behavior favors the precoupled mechanism, A + R.E: formula: (see text), where the receptor R and the enzyme E are permanently coupled to each other and the adenosine A binds to the receptor and induces the first-order process of cyclase activation to its active form ARE'. The finding that adenosine receptor is permanently coupled to the cyclase catalytic unit is corroborated by the observation that the progressive increase in membrane fluidity has no effect on the rate constant (k3) of adenylate cyclase activation by the adenosine-adenosine receptor complex and that the dose-response curve for adenosine is noncooperative.

Adenosine

Acute and chronic pulmonary function changes in allergic bronchopulmonary aspergillosis.

Pulmonary functions of patients with allergic bronchopulmonary aspergillosis were studied during an acute episode (n = 6); during a mean follow-up period of 44 months (range four months--14.8 years) (n = 16); and for any correlation between duration of ABPA and asthma with the total lung capacity (helium dilution), 1 second forced expiratory volume (FEV1), vital capacity, 1 second forced expiratory volume-forced vital capacity ratio (FEV1:FVC per cent) and diffusing capacity of carbon monoxide (DL:CO) (single breath) for the entire group (n = 22). All patients were treated with corticosteroids (intermittent or continuous) and bronchodilators. For the 16 patients, slopes using linear regression analysis were determined from the function as per cent predicted versus time in months from diagnosis and then analyzed for significance. Significant functional loss was shown in three of 16 patients for FEV1, two of 16 patients for vital capacity, one of 16 patients for FEV1:FVC per cent, none of 10 patients for DL:CO and one of 10 patients for total lung cital capacity, FEV1:FVC per cent and the duration of asthma or allergic bronchopulmonary aspergillosis was found by multiple regression analysis correcting for age and smoking (mean 4.24 years; range 0.3 to 14.8 years). Roentgenographic criteria and blood eosinophilia were used to define a "flare" of allergic bronchopulmonary aspergillosis. The six patients during a flare showed a significant reduction in total lung capacity (P less than 0.001), vital capacity (P less than 0.05), FEV1 (P less than 0.01) and DL:CO (P less than 0.001) which uniformly returned to baseline values during steroid therapy. The FEV1:FVC per cent remained unaltered. These findings, contrary to suggestions in the literature, indicate that in the majority of our patients there was no significant progressive functional deterioration after diagnosis. However, during acute episodes of allergic bronchopulmonary aspergillosis, transient reduction of volumes and DL:CO were uniformly present.

Adolescent