PubMed Health⌕ Search

Biomedical subjects

B Alvarez

Publications and source records attributed to B Alvarez.

At least 73 records · Page 4Linked to original sources

Dissociation between positive inotropic and alkalinizing effects of angiotensin II in feline myocardium.

The present study examines the intracellular pH (pHi) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30 degrees C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pHi and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 microM). The positive inotropic effect of ANG II peaked at 9.7 +/- 0.8 min (240 +/- 57% above control) without significant changes in pHi. The increase in pHi became significant (0.05 +/- 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant pHi changes. In the presence of 5 microM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in pHi, despite which ANG II still increased contractility by 87 +/- 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a pHi change, whereas in a physiological CO2-HCO3- medium the positive inotropic effect of ANG II is independent of pHi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pHi, as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3- medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pHi.

Ammonium Chloride↗

Monoclonal antibody 2F4/11 recognizes the alpha chain of a porcine beta 2 integrin involved in adhesion and complement mediated phagocytosis.

The characterization of a new mAb, named 2F4/11, specific for porcine myelomonocytic cells is described. This mAb immunoprecipitates a non-covalently linked heterodimer of 155,000/95,000, which is expressed by granulocytes, monocytes and tissue macrophages but not by lymphocytes, erythrocytes or platelets. Immunoblot analysis localizes the 2F4/11 epitope on the largest subunit of the heterodimer. Mab 2F4/11 is able to block phagocytosis of complement-opsonized zymosan particles by PMN granulocytes and alveolar macrophages, as well as adherence to plastic surfaces of PMA-activated PMN. Together, these results suggest that mAb 2F4/11 recognizes the CD11b or alpha chain of the porcine complement type 3 receptor (CR3).

Animals↗

A predictive model for the treatment approach to community-acquired pneumonia in patients needing ICU admission.

OBJECTIVE: To create a predictive model for the treatment approach to community-acquired pneumonia (CAP) in patients needing Intensive Care Unit (ICU) admission. DESIGN: Multicenter prospective study. SETTING: Twenty-six Spanish ICUs. PATIENTS: One hundred seven patients with CAP, all of them with accurate etiological diagnosis, divided in three groups according to their etiology in typical (bacterial pneumonia), Legionella and other atypical (Mycoplasma, Chlamydia spp. and virus). For the multivariate analysis we grouped Legionella and other atypical etiologies in the same category. METHODS: We recorded 34 variables including clinical characteristics, risk factors and radiographic pattern. We used a multivariate logistic regression analysis to find out a predictive model. RESULTS: We have the complete data in 70 patients. Four variables: APACHE II, (categorized as a dummy variable) serum sodium and phosphorus and "length of symptoms" gave an accurate predictive model (c = 0.856). From the model we created a score that predicts typical pneumonia with a sensitivity of 90.2% and specificity 72.4%. CONCLUSION: Our model is an attempt to help in the treatment approach to CAP in ICU patients based on a predictive model of basic clinical and laboratory information. Further studies, including larger numbers of patients, should validate and investigate the utility of this model in different clinical settings.

APACHE↗

Peroxynitrite-dependent tryptophan nitration.

Peroxynitrite (ONOO-), the reaction product of superoxide (O2.-) and nitric oxide (.NO), nitrates tyrosine and other phenolics. We report herein that tryptophan is also nitrated by peroxynitrite in the absence of transition metals to one predominant isomer of nitrotryptophan, as determined from spectral characteristics and liquid chromatography-mass spectrometry analysis. At high peroxynitrite to tryptophan ratios, other oxidation products were detected as well. The amount of nitrotryptophan formed from peroxynitrite increased at acidic pH, with an apparent pKa of 7.8. High concentrations of Fe(3+)-EDTA were required to enhance peroxynitrite-induced nitrotryptophan formation, while addition of up to 15 microM Cu/Zn superoxide dismutase had a minimal effect on tryptophan nitration. Cysteine, ascorbate, and methionine decreased nitrotryptophan yield to an extent similar to that predicted by their reaction rates with ground-state peroxynitrite, and typical hydroxyl radical scavengers partially inhibited nitration. Plots of the observed rate constant of nitrotryptophan formation vs tryptophan concentration presented downward curvatures. Thus, the kinetics of metal-independent nitration reactions were interpreted in terms of two parallel mechanisms. In the first one, ground-state peroxynitrous acid nitrated tryptophan with a second-order rate constant of 184 +/- 11 M-1 s-1 at 37 degrees C. The activation enthalpy was 9.1 +/- 0.3 kcal mol-1, and the activation entropy was -19 +/- 1 cal mol-1 K-1. In the second mechanism, ONOOH*, an activated intermediate derived from trans-peroxynitrous acid formed in a steady state, was the nitrating agent.

Deferoxamine↗

Severe community-acquired pneumonia in the elderly: epidemiology and prognosis. Study Group for Severe Community-Acquired Pneumonia.

Ninety-five patients with severe community-acquired pneumonia (SCAP) who were > or = 65 years of age were studied prospectively. A definite pathogen was identified in 37 cases (38.9%) and was most commonly Streptococcus pneumoniae, Haemophilus influenzae, or another gram-negative bacillus. The overall death rate was 40%. Eighty-three patients required mechanical ventilation and 40 needed vasoactive drugs. Multivariate analysis showed that the risk of death was higher in cases involving rapid radiological spread (relative risk [RR] = 6.99; 95% confidence interval (95% CI) = 1.54-31.70), shock (RR = 6.70; 95% CI = 2.13-21.02), previous steroid treatment or immunosuppression (RR = 5.50; 95% CI = 0.77-39.10), acute renal failure (RR = 3.88; 95% CI = 1.30-11.59), or an APACHE II score of > 22 on admission (RR = 2.25; 95% CI = 0.73-6.95). We conclude that SCAP in elderly patients is associated with high mortality, but it is inappropriate to withhold intensive care on account of age. The presence of complications and the severity of illness at initial presentation were the major variables affecting outcome. Except for immunosuppression, comorbidities did not seem to influence outcome. Finally, our data reinforce the current American Thoracic Society guidelines concerning therapy for patients with SCAP.

Acute Kidney Injury↗

Mechanism of negative lusitropic effect of alpha 1-adrenoceptor stimulation in cat papillary muscles.

Experiments were performed in cat papillary muscles to explore the mechanisms by which alpha 1-adrenoceptor stimulation affects myocardial relaxation. Phenylephrine (PE; 10 microM) + atenolol (1 microM; n = 8 experiments) produced a negative lusitropic effect, i.e., a prolongation of half-relaxation time (t1/2; time to 50% relaxation) by 30 +/- 10% (P < 0.05) and a proportionally smaller increase in maximal velocity of relaxation (-T) than in maximal velocity of contraction (+T), which significantly increased the ratio +T/-T. A similar increase in contractility, produced by increasing calcium, failed to significantly change t1/2 and +T/-T. PE-induced negative lusitropic effect was significantly inhibited by two protein kinase C (PKC) inhibitors, staurosporine (0.1 microM) and chelerythrine (10 microM). PE also increased intracellular pH by 0.18 +/- 0.05 pH units (P < 0.05, n = 4), as measured by the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Intracellular alkalosis and the negative lusitropic effect of PE were prevented by the Na+/H+ exchanger inhibitor ethylisopropylamiloride (10 microM). No significant changes in calcium myofilament sensitivity and maximal tension were detected in trabeculae treated with PE either before or after chemical skinning. These results indicate that a Na+/H+ exchanger-induced intracellular alkalosis, possibly mediated by PKC activation, may fully account for the negative lusitropism of alpha 1-adrenoceptor stimulation.

Actin Cytoskeleton↗

Reaction between peroxynitrite and hydrogen peroxide: formation of oxygen and slowing of peroxynitrite decomposition.

Peroxynitrite, the reaction product of nitric oxide and superoxide, is a potent and versatile oxidant that can attack a wide range of targets. In this work, we studied the oxidation of hydrogen peroxide by peroxynitrite, which led to oxygen evolution. Oxygen yields increased at alkaline pH with an apparent pKa of 7.05 +/- 0.04. The maximum yields were 16% and 32% of added peroxynitrite at pH 5.9 and 7.4, respectively, assuming that two molecules of peroxynitrite are needed to produce one of oxygen. Hydroxyl radical scavengers (dimethyl sulfoxide, mannitol, ethanol, formate, and acetate) inhibited oxygen evolution to a similar extent to that predicted from their rate constants with hydroxyl radical. The apparent rate constant of peroxynitrite decomposition was zero-order in hydrogen peroxide at acidic pH. At neutral and alkaline pH, the rate of peroxynitrite disappearance decreased in the presence of millimolar concentrations of hydrogen peroxide by up to 50%. The apparent activation enthalpy and entropy for peroxynitrite decomposition increased by 1.7 kcal mol-1 and 4.7 cal mol-1 K-1, respectively, in the presence of hydrogen peroxide. We propose that an activated intermediate of peroxynitrous acid is responsible for hydrogen peroxide oxidation at acidic pH, while at more alkaline pH the formation of a stabilizing complex between hydrogen peroxide and transperoxynitrite anion is involved.

Hydrogen Peroxide↗

[Radiofrequency ablation of the slow nodal pathway in cases of paroxysmal nodal reentry tachycardia].

INTRODUCTION: We describe our experience in the treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of the slow pathway. PATIENTS AND METHODS: Thirty-four patients (mean age 52 +/- 13 years) with recurrent drug refractory atrioventricular nodal reentrant tachycardia underwent radiofrequency catheter ablation of slow-pathway as the first procedure. Maximal energy used was 28 +/- 8 W, mean time was 4.4 +/- 2.8 min, and a mean number of 13 +/- 9 discharges per patient. RESULTS: Of the 34 patients 14 were successfully treated (no slow-pathway conduction, no AV nodal reentrant echo complexes, no inducible tachycardia), 11 were considered as partially successful (no inducible tachycardia, with slow-pathway conduction or echoes) and 9 patients were unsuccessfully treated (all of them underwent fast-pathway ablation with a successful outcome). Eight recurrences were observed during a mean follow-up period of 7 +/- 4 months: One in a patient with previously successful ablation (remained asymptomatic while taking beta-blockers), 6 in patients with first procedure partially successful (all of them underwent effective second slow-pathway ablation) and 1 in a patient with an unsuccessful procedure that underwent fast pathway ablation. A repeated procedure was successful in ablating the slow pathway. None of our patients developed complete atrio-ventricular block. One patient developed cardiac tamponade that needed surgical drainage. At last follow-up all patients are free from tachycardias. CONCLUSION: Slow pathway ablation is an effective method of treatment in patients with atrio-ventricular nodal reentrant tachycardia. Long term success is related to complete abolition of slow pathway conduction.

Adolescent↗

Can selective digestive decontamination avoid the endotoxemia and cytokine activation promoted by cardiopulmonary bypass?

OBJECTIVE: To evaluate the effect of selective digestive decontamination on endotoxemia and cytokine activation during the ischemic phase of cardiopulmonary bypass surgery. DESIGN: Prospective, open, randomized, controlled trial. SETTING: Two multidisciplinary intensive care units in tertiary care hospitals. PATIENTS: Eighty consecutive patients randomly allocated to two groups: selective digestive decontamination (group 1, n = 40) and controls (group 2, n = 40). INTERVENTIONS: Preoperative administration of oral antibiotics (polymyxin E, tobramycin, and amphotericin B) vs. untreated controls. MEASUREMENTS AND MAIN RESULTS: Assessment of decontamination by bacteriologic evaluation of rectal swabs (colony-forming units [cfu]/mL) were made in each group, along with circulating endotoxin, tumor necrosis factor and interleukin-6 (IL-6) determinations before surgery, during ischemic and reperfusion phases of bypass, and at 4 hrs and at 24 hrs after surgery. Group 1 patients showed that rectal bacteria decreased ten-fold after treatment for 24 hrs, thousand-fold after 48 hrs, and registered 0 cfu/mL after digestive decontamination was administered for > 72 hrs. Endotoxin and IL-6 assays showed significantly lower values in this latter group vs. those circulating concentrations of control patients. On the other hand, both endotoxin and IL-6 concentrations correlated positively with the duration of surgical ischemia. CONCLUSIONS: Selective digestive decontamination reduces the gut content of enterobacteria, with complete elimination after 3 days of treatment. This fact could explain the lower endotoxin and cytokine concentrations found in the blood samples of patients who had been fully decontaminated. Duration of aortic cross-clamping is an important factor in generating endotoxemia and in the activation of cytokines.

Adult↗

The delayed sleep phase syndrome: clinical and investigative findings in 14 subjects.

Fourteen subjects are described in whom a clinical diagnosis of the delayed sleep phase syndrome was made. The condition is multi-factorial, dependent on lifestyle, mood and personality, as well as on familial factors but no single factor in isolation is sufficient to explain the delay in sleep timing. Refusal to attend school may be important in some instances but will not explain cases with delayed age of onset. In half the subjects the delay in sleep phase started in childhood or adolescence. The syndrome causes severe disruption to education, work and family life. Polysomnography, motor activity monitoring of rest-activity cycles, plasma melatonin profiles and urinary melatonin metabolite excretion are normal. Different patterns of sleep phase delay seen in the syndrome include stable, progressive, irregular and non-24 hour sleep-wake cycles. These patterns may result from different social and other Zeitgebers ("time-markers", for example sunrise, sunset) in the normal environment. Treatment by forced sleep-wake phase advance or with melatonin resulted in a partial sleep-phase advance but this was not maintained on stopping treatment.

Adolescent↗

Delayed sleep phase syndrome response to melatonin.

The actions of melatonin on the sleep-wake cycle were investigated by means of a randomised, double-blind, placebo-controlled trial in 8 subjects with a delayed sleep phase syndrome attending a sleep disorders clinic. In randomised order the subjects received placebo or melatonin 5 mg daily for 4 weeks with a 1 week washout period between the treatments. Drug or placebo was given at 2200 h, 5 h before the mean time of sleep onset determined by pretrial sleep logs. In all 8 subjects sleep onset time (mean advance 82 [range 19-124] min; p less than 0.01) and wake time (117 [10-187] min; p less than 0.01) were significantly earlier during melatonin treatment than during placebo. Mean total sleep time was slightly less on melatonin (8 h 12 min) than on placebo (8 h 46 min). Alertness acrophase calculated from the subjects' ratings of alertness made every 2 h while awake was unaltered. Melatonin may act as a phase-setter for sleep-wake cycles in subjects with a delayed sleep phase syndrome.

Administration, Oral↗

ICU pneumonias: a multi-institutional study.

We conducted a prospective multi-institutional study of nosocomial and community-acquired pneumonias in 1378 patients admitted to the ICUs of six hospitals. We also investigated 1005 of these patients who were intubated and mechanically ventilated for a reason other than pneumonia, the risk of developing pneumonia, and the relationship between the incidence of pneumonia and the length of time during which the patients were mechanically ventilated. A bacteriologic diagnosis was made in 38% of the nosocomial and 21% of the community-acquired pneumonias. The total mortality rate was 40%; 47% of the patients with nosocomial and 17% of the patients with community-acquired pneumonias died. Because it was difficult to make an etiologic diagnosis in two-thirds of the cases, the treatment had to be based on an assumed causative organism.

Adult↗