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Biomedical subjects

L Alvarez

Publications and source records attributed to L Alvarez.

At least 217 records · Page 12Linked to original sources

Detection of creatine kinase isoenzymes as tumoral markers of rhabdomyosarcoma.

We analyzed the expression profile of isoenzymatic fractions of creatine phosphokinase (EC 2.7.3.2) isotypes MM, MB and BB in three cell lines derived from embryonic rhabdomyosarcomas and a normal counterpart cell line. Electrophoretic data showed that the BB fraction was consistently expressed de novo, in contrast with its counterpart in normal tissue. The BB fraction may serve as new tumoral marker for the diagnosis of rhabdomyosarcoma. In addition, the appearance of macrocreatine kinase type-1 in this type of neoplasm may serve to reinforce the diagnosis when rhabdomyosarcoma is suspected.

Biomarkers, Tumor↗

Are contraction and relaxation coupled in patients with and without congestive heart failure?

BACKGROUND: Although changes in contractility are often accompanied by changes in relaxation, a mathematical model of ventricular coupling has not been described. A model we examined suggests a hyperbolic relation between measurements of contraction and relaxation. We thus tested the hypothesis that relatively load-independent measurements of contractility (end-systolic elastance [Ees]) and relaxation (the slope of the tau-to-end-systolic pressure relation [R]) were coupled. METHODS AND RESULTS: To establish the validity of the model, an assessment of Ees and R was made in 30 subjects who underwent sequential digital ventriculography and micromanometer pressure measurements during atrial pacing (93 +/- 10 min-1) before and after graded doses of nitroprusside. To establish if a cyclic AMP (cAMP)-mediated intervention alters coupling, seven of the 30 subjects were studied before and after 3 months of beta-blockade. To determine if a non-cAMP-mediated intervention alters coupling, 12 other patients were studied before and after deslanoside. Nonlinear regression analysis for the initial 30 patients suggested a hyperbolic relation: (Ees) (R) = 1.05 (r = 0.79, p less than 0.001) with an inflection point near Ees = 1.02 mm Hg/ml. Thus, with normal or near-normal contractility, relaxation is normal and not load dependent (R is close to 0). With systolic dysfunction, relaxation becomes very afterload dependent and so must be normalized for load. After long-term beta-blockade in patients with severe left ventricular dysfunction, small improvements in contractility (elastance) occurred with larger changes in relaxation, but the curve describing the relation was not displaced. Acute administration of deslanoside resulted in a large increase in elastance and a smaller change in relaxation but did not alter coupling. However, the magnitude of the change in R was dependent on the predrug R value. CONCLUSIONS: These data suggest contraction and relaxation may be physiologically coupled with relaxation relatively preserved in early heart failure and more rapid deterioration in relaxation as elastance falls under 1.02 mm Hg/ml. Both beta-blockers (which may act through cAMP) and digitalis (which is cAMP independent) improve contraction and relaxation, but both mechanisms appear to maintain coupling. The hyperbolic relation between contraction and relaxation may have important implications regarding therapeutic response and selection of patients for clinical trials in heart failure.

Adrenergic beta-Antagonists↗

Effectiveness of atenolol in the treatment of hypertension during pregnancy.

This study assessed the effectiveness of atenolol in the treatment of moderate and severe hypertension during pregnancy. Seventy patients (mean age, 30.3 +/- 6.0 years), 35.7% primiparous, were included. Three groups were formed according to Davey and MacGillivray's classification: 1) chronic hypertension without proteinuria (12 patients), 2) gestational hypertension without proteinuria (52 patients), and 3) preeclampsia (six patients). Treatment with atenolol was started when blood pressure was 150/100 mm Hg or higher after 48 hours' rest. The treatment lasted at least 1 week; follow-up was every 2 weeks up to week 36, and from then on, weekly up to delivery. If blood pressure exceeded 160/110 mm Hg and the fetus was not yet mature, a second drug was added. A significant decrease in blood pressure was observed in the three groups (group 1: 155.8 +/- 15.0/100.8 +/- 7.6 versus 135.0 +/- 12.9/85.0 +/- 6.7 mm Hg; group 2: 154.2 +/- 13.6/104.9 +/- 9.3 versus 129.6 +/- 10.2/83.7 +/- 9.1 mm Hg; group 3: 158.3 +/- 27.1/104.1 +/- 8.0 versus 129.1 +/- 6.6/87.5 +/- 6.1 mm Hg). The doses of atenolol were 62.5 +/- 23.0 mg/day in group 1, 70.0 +/- 30.0 mg/day in group 2, and 100.0 +/- 41.0 mg/day in group 3. There was no fetal mortality. No significant difference occurred in newborn body weights. Four babies from group 2 mothers had an Apgar score of less than 7 at 1 minute, but only one remained abnormal after 5 minutes. In the same group, three cases of respiratory distress were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ictal head deviation: lateralizing significance of the pattern of head movement.

To resolve the controversy surrounding the lateralizing value of ictal head deviation, we analyzed head-turning movements in relation to the actions of the two divisions of the sternocleidomastoid muscle. In 12 (75%) of 16 patients with surgically confirmed lateralized seizure foci, the face rotated upward and contraversive to the hemisphere of seizure origin, consistent with activation of the ipsilateral sternomastoid muscle. One patient showed a sustained, downward ipsiversive head tilt consistent with the action of the ipsilateral cleidomastoid muscle, and three patients had a combined ipsiversive head tilt and contraversive face rotation. No patient exhibited ipsiversive upward face rotation or contraversive head tilting, as would be expected if the contralateral sternocleidomastoid were activated. Our findings indicate that hemispheric seizure foci activate one or both divisions of the ipsilateral sternocleidomastoid muscle. Accurate lateralization of the seizure focus is possible only when ictal head deviation is assessed in the context of the different actions of the sternomastoid and cleidomastoid muscle divisions.

Adolescent↗

Late sudden cardiac death in the follow-up of patients having a heart valve prosthesis.

Eight hundred thirty-one patients with Björk-Shiley prostheses (341 aortic, 345 mitral, and 145 double) had a mean follow-up time of 68.2 months per patient. Of these, 24 (16% of all deaths) died suddenly: six of 42 with aortic valve replacement (14.3%), 12 of 56 with mitral valve replacement (21.4%), and six of 36 with double valve replacement (16.6%). This correlated with evidence of premature ventricular complexes detected in multiple routine 12-lead follow-up electrocardiograms (p less than 0.001 for simple aortic or mitral valve replacements and p less than 0.01 for combined aortic and mitral valve replacements). Premature ventricular complexes were significantly more frequent among those who died suddenly than among survivors and those who died of other causes (p less than 0.001 in both cases); there were no significant differences between the latter two groups. The actuarial risk of sudden death was significantly greater among those patients who had premature ventricular complexes than among those who did not have this disorder (p = 0.0002). We conclude that the presence of premature ventricular complexes, as an independent variable, was correlated with the risk of sudden death.

Adult↗

The Björk-Shiley valve prosthesis. Analysis of long-term evolution.

The long-term follow-up of 831 patients who underwent valve replacement with Björk-Shiley Delrin and standard Pyrolyte prostheses (341 aortic, 345 mitral, and 145 mitroaortic) between 1971 and 1980 is reviewed. The follow-up concluded in 1985. Cumulative follow-up amounted to 4724 years, with a mean of 5.68 years per patient. Data on survival were obtained in 754 patients (complete follow-up in 90.8% of cases). Perivalvular leak was the most frequent complication in aortic valve replacement, whether isolated or combined, with values significantly higher than those registered in isolated mitral replacement (p < 0.001 in both cases). No correlation was found between this complication and valve calcification, but it was statistically correlated with the size 19 model (p < 0.05). Prosthetic stenosis was more common in mitral than in aortic replacement (p < 0.001), and of the former, size 23 was that most often affected (p < 0.001). The earliest case of mitral pannus was diagnosed 20 months postsurgery, and from 45 months on this pathology was the cause of every case of stenosis. The risk of thromboembolism was similar in aortic, mitral, and double prostheses, while it was the single most frequent complication in isolated mitral replacement. Prosthetic thrombosis was triggered in all cases in which it occurred by discontinuance of anticoagulant therapy. Anticoagulant-induced hemorrhages were more frequent in double replacement than in mitral (p < 0.05) and aortic valve replacement. Endocarditis was the complication that produced the highest mortality rate in all groups; the frequency of this infection was higher among patients with double prostheses when compared with either aortic replacement (p < 0.05) or mitral replacement (p < 0.001). The risk of suffering endocarditis was correlated with the existence of active preoperative infection in patients with mitral prostheses and double prostheses (p < 0.001 in both cases). Overall morbidity was higher in the double replacement group with respect to the mitral group (p < 0.01). The rate of mortality was also higher among the double valve replacement patients when compared with both the aortic (p = 0.0002) and mitral (p = 0.006) groups.

Actuarial Analysis↗

Analysis of the 5' non-coding region of rat liver S-adenosylmethionine synthetase mRNA and comparison of the Mr deduced from the cDNA sequence and the purified enzyme.

A 3 kb cDNA coding for rat liver S-adenosylmethionine (AdoMet) synthetase has been isolated. The Mr of the protein has been unequivocally determined by cDNA sequencing and enzyme purification on a thiopropyl-Sepharose column. The length of the mRNA 5' non-coding region has been defined by primer-extension analysis. The rat liver cloned cDNA has been also used to detect S-adenosylmethionine synthetase mRNA in human liver.

Animals↗

Imipramine-fentanyl antinociception in a rabbit tooth pulp model.

Antinociception of imipramine (I) and its effect in combination with fentanyl (F) was evaluated in rabbits using electrically-induced lick chew responses via tooth pulp stimulation as the model of nociception. Acute i.v. injections of I elicited a graded dose response comparable to i.v. morphine (M) with I ED 50 = 4.35 mg/kg (2.31-8.14, 95% CL) and M ED 50 = 1.81 mg/kg (1.11-3.90), with no differences in the slopes between the two curves. The lethal dose of I was 10 mg/kg. An i.v. dose of I twice the ED 50 elicited an antinociceptive effect of more than 50% maximum possible effect (MPE) for 90 minutes with peak effect of 82% MPE occurring at 15 minutes. These effects of I were not reversed by a morphine-reversal dose of naloxone (0.1 mg/kg i.v.) but were reversed with a ten fold dose of naloxone. F ED 50 values (mcg/kg) were lowered from 11.35 to 2.70, 0.74 and 0.33 with increasing pretreatment doses of I (1.0, 2.1 and 3.2 mg/kg). These magnitudes of potency increases of F were 4.2, 15.3 and 34.4 fold respectively. A single i.v. ED 50 dose of I extended the time to 50% MPE of an ED 90 dose of F from 26 minutes to 77 minutes; of a 2 X ED 50 dose of F from 17 minutes to 28 minutes. Data points for three different combinations of I and F fell significantly within the synergistic field of an ED 50 isobologram and a polynomial equation described the curve best fitting the data points. F alone (i.v. ED 50 dose) increased the PaCO2 values to 74% above controls and three different combinations with I showed no increases in PaCO2 values above controls. I alone did not significantly cause any change in PaCO2 values from controls.

Analgesics↗

Influence of fibric acid derivatives on intermediate filament proteins in myocardiocyte cultures.

We analyzed desmin and vimentin accumulation in chick myocardiocyte cultures treated with the fibric acid derivatives bezafibrate, fenofibrate and gemfibrozil. The most noteworthy finding was the 50% decrease in the cytoplasmic desmin fraction in cells treated with gemfibrozil in comparison to control cultures, and the 19% increase in the cytoskeletal fraction in cultures treated with gemfibrozil and with bezafibrate. Vimentin accumulation by cells treated with bezafibrate was similar to that in control cultures, however the cytoskeletal vimentin fraction rose by 26% after treatment with gemfibrozil, and fell 13% after treatment with fenofibrate. No vimentin was found in the cytoplasmic fraction of cell treated with bezafibrate. Given the role of intermediate filaments in heart muscle contraction, fibric acid derivative- induced changes in the cytoplasmic and cytoskeletal concentrations of intermediate filament proteins may be related with the secondary effects of these drugs on heart rate.

Animals↗

Effects of fibric acid derivatives on accumulation of actin in myocardiocytes.

We used sodium dodecylsulphate polyacrylamide gel electrophoresis and immunoblotting to analyze the effects of the fibric acid derivatives bezafibrate, fenofibrate and gemfibrozil on the accumulation of actin in the cytoplasmic and cytoskeletal fraction of cultured myocardiocytes. All three drugs tested modified cellular and subcellular actin in different ways, and the findings are thought to be related with the secondary effect of arrhythmia known to be caused by these drugs. Bezafibrate and gemfibrozil more markedly affected accumulation of actin by myocytes, while fenofibrate interfered less notably with the accumulation of this protein.

Actins↗

Morphometric data on the arterial duct in the human fetal heart.

In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the ascending aorta, the descending aorta, the aortic isthmus, the right pulmonary artery, the left pulmonary artery and the arterial duct. In all, nine different parameters were measured in each specimen. The variations in the correlations between two measurable characteristics, namely body weight and each of the morphometric parameters, were analyzed. The minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. We compared statistically the diameter of the arterial duct with the diameter of the ascending and descending aorta, the aortic isthmus, the right pulmonary artery and the left pulmonary artery with one way analysis of variance, using Bonferroni's test in the pairwise comparisons. The diameter of the arterial duct was smaller than the diameter of the ascending and descending aortas, the aortic isthmus, the right pulmonary artery and the left pulmonary artery, and the diameter of the ascending aorta was larger than that of the descending aorta. These morphological data have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders.

Aorta↗

Diagnostic value of two-dimensional echocardiography in cardiac hydatid disease.

Echinococcal infection of the heart is rare. The preoperative findings, with special attention to two-dimensional echocardiography (2DE), of six patients with cardiac echinococcosis and their surgical and pathological correlations are reported. Cardiac hydatid cysts (HCs) were located in the cardiac apex in three patients, in the upper part of the interventricular septum extending towards the anterior aspect of the heart in one and in the postero-superior right atrial wall in another patient. The remaining patient had multiple intrapericardial cysts. In three patients the cysts presented as well defined, rounded, echolucent masses within the myocardial wall bulging into the cardiac chambers. In two patients, the cysts had ruptured into a cardiac chamber with loss of the characteristic 'cystic' appearance; these cysts presented as an echogenic or solid mass protruding into a cardiac chamber. Finally, another patient had one HC with echolucent appearance and another HC in a different location with echogenic appearance; this last cyst corresponded to a degenerated HC. In two cases the cyst showed a loculated internal aspect. In one patient the myocardial segment involved by the cyst had a dyskinetic movement. In all six patients, 2DE accurately demonstrated the location and morphological details of the cardiac cysts, permitted recognition of the ruptured and/or degenerated cysts and was superior to thoracic computed tomography and angiography in the preoperative assessment of these patients. Nuclear magnetic resonance imaging (one patient) gave no further information to that obtained by 2DE. We conclude that 2DE is the technique of choice for an early diagnosis of this rare entity.

Adult↗

Insulin-like effects of inositol phosphate-glycan on messenger RNA expression in rat hepatocytes.

The ability of an inositol phosphate-glycan (IPG) to mimic the effects of insulin on regulation of the expression of specific mRNAs was studied in isolated hepatocytes from normal and diabetic rats. Incubation of normal liver cells with IPG (10 microM) during 90 min produced a 5-fold decrease in phosphoenolpyruvate carboxykinase (PEPCK) mRNA levels, which had been previously increased about 10-fold by incubation with 8-bromo-cAMP (0.1 mM). The effect of IPG was dose dependent and could not be reproduced by galactose, glucosamine, or myo-inositol. IPG reduction of PEPCK mRNA is primarily due to a decrease in the rate of transcription of the gene, as judged by nuclear run-on transcription experiments performed in rat hepatoma H4IIE cells. In hepatocytes isolated from diabetic rats, treatment with 5 microM IPG for 15 min caused a 4-fold induction in the expression of alpha 2-microglobulin mRNA concomitantly with a 2.5-fold decrease in the level of PEPCK mRNA. Cleavage of IPG with nitrous acid abolished both the increase and the decrease in specific mRNAs levels. Glycosyl-phosphatidylinositol, the lipid precursor of IPG, did not modify either PEPCK or alpha 2-microglobulin mRNA levels. These data indicate that both positive and negative effects of insulin on the regulation of gene expression are mimicked by IPG.

8-Bromo Cyclic Adenosine Monophosphate↗

Morphometric data concerning the great arterial trunks and their branches.

In a total of 496 fetuses and newborns ranging in body weight from 60 to 5000 g, we performed a morphometric study of the vascular complex, that is the orifices of the great arterial trunks, ascending aorta, aortic arch, vessels branching from the aortic arch, the aortic isthmus, descending aorta, pulmonary trunk, orifices of the pulmonary arteries and arterial duct. In all, 17 different parameters were measured in each specimen, using several new parameters in addition to the measurements classically used in the aortic isthmus, arterial duct and pulmonary trunk. Anatomo-geometric models of these structures were developed, and stereometric formulas used to calculate the real volumes of the aortic isthmus, arterial duct and pulmonary trunk. The variations in the correlations between two measurable characteristics, that is, body weight and each of the morphometric parameters were analyzed, and the minimum, normal and maximum patterns of normality for each parameter were obtained with regression equations. The results show that the volume of the aortic isthmus increases by 0.03 ml for each millilitre increase in left ventricular volume. The isthmic volume increases by 0.32 ml for each millilitre increase in volume of the arterial duct and the volume of the pulmonary trunk increases by 6.4 ml for each increase of 1 millilitre in the volume of the aortic isthmus. The inner circumference of the aortic isthmus is greater than that of the arterial duct, whereas the former vessel is always shorter than the latter. We believe that these morphological data, when appropriately interpreted, have immediate clinical and surgical applications in the treatment of fetal and perinatal cardiovascular disorders.

Aorta↗

Electrophysiology of heterotopic heart transplant: experimental study in dogs.

Electrophysiological properties were studied in a heterotopic heart transplant model developed in 44 dogs (Group I). Cycle length was 359.5 +/- 55.2 ms in the recipient heart and 500.9 +/- 77.9 ms in the donor heart (P less than 0.001). Sinoatrial conduction time was 38.6 +/- 13.6 ms in the recipient heart and 38.6 +/- 10.4 ms in that of the donor (not significant). The Wenckebach point was 175.4 +/- 31.1 ms in the recipient organ and 214.3 +/- 42.6 ms in the donor heart (P less than 0.001). The retrograde block point was 271.6 +/- 48.0 ms in the recipient heart and 353.6 +/- 47.3 ms in that of the donor (P less than 0.01). The effective antegrade refractory period was 133.4 +/- 28.7 ms in the recipient heart and 167.3 +/- 46.3 ms in the donor organ (P less than 0.001). An epicardial atrial cartography was performed at 44 preset points in both hearts, revealing a normal activation sequence and delays of 36-98 ms (mean 58 ms) in the recipient heart and from 39 to 59 ms (mean 50 ms) in the donor heart (not significant). In another 11 dogs (Group II), the same electrophysiological study was carried out under basal conditions and after pharmacological blockade of the autonomic nervous system with atropine (0.04 mg (kg body weight)-1) and propranolol (0.2 mg (kg body weight)-1). No significant differences were found in any of the parameters studied upon comparison of Group II animals in basal conditions with Group I recipients, and Group II dogs after blockade with Group I donors. These results demonstrate that the differences in automatism, conduction and refractoriness between the donor and recipient hearts are not attributable to differences in the haemodynamic situation or in the anaesthetic technique, but to denervation.

Animals↗