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Biomedical subjects

A Esteban

Publications and source records attributed to A Esteban.

At least 55 records · Page 3Linked to original sources

A randomized and controlled trial of the effect of treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock.

OBJECTIVE: To evaluate the effects of increased oxygen delivery on mortality and morbidity. DESIGN: Randomized, controlled trial. SETTING: Medical-surgical ICU of a tertiary care hospital. PATIENTS: Sixty-three patients classified according to predetermined criteria as having severe sepsis or septic shock. INTERVENTIONS: The patients were randomly assigned to one of two groups: the control group (n = 32) received conventional therapy with a normal targeted value of oxygen delivery, and the treatment group (n = 31) received therapy with a targeted oxygen delivery index (DO2I) value of > 600 mL/min/m2. The therapeutic approach to maintain BP, arterial saturation, hemoglobin concentration, and pulmonary artery occlusion pressure was similar in both groups. MEASUREMENTS AND MAIN RESULTS: The hemodynamic, oxygen transport, and gastric intramucosal pH measurements were recorded at the time of admission to the study and every 6 h for the next 96 h. The outcome measures were the rate of patient mortality and the number of organ dysfunctions occurring during the ICU stay. The study groups were similar with respect to demographics and admission hemodynamic variables, but the percentage of patients with positive blood cultures was significantly higher in the control group than in the treatment group, respectively: 34 vs 13% (p = 0.04). The average cardiac index was significantly higher in the treatment group than in the control group, respectively: 3.96 vs 3.05 L/min/m2 (p = 0.01). This factor did not significantly affect the DO2I. Nine of the 31 treatment group patients reached an average DO2I value of > 600 mL/min/m2. The rate of mortality in the control group patients up to the time of ICU discharge (66%) was similar to that seen in the treatment group (74%), respectively: 21 of 32 vs 23 of 31 (p = 0.46). The number of dysfunctional organs per patient was also similar in the control and treatment groups, respectively: 2.1+/-1.1 vs 2.6+/-1.2 (p = 0.12). CONCLUSION: Treatment aimed at maximizing oxygen delivery in patients with severe sepsis or septic shock does not reduce mortality or morbidity.

Aged↗

Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric oxide synthesis by human neutrophils.

Recent studies have suggested that the protective anti-ischemic effects of acetylsalicylic acid are stronger than the inhibition of platelet thromboxane A2 synthesis. Since ischemic events still occur in acetylsalicylic acid-treated patients, the development of new drugs with more powerful protective effects is needed. We compared the effects of a new platelet antiaggregating drug, 2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and of acetylsalicylic acid on the interaction between human neutrophils and platelets, examining the capability of neutrophils to generate nitric oxide (NO). Triflusal, in the presence of neutrophils, showed a greater antiplatelet potency than acetylsalicylic acid to inhibit thrombin-induced platelet activation. Significant stimulation of NO-mediated mechanisms in the presence of acetylsalicylic acid or triflusal was demonstrated by the following findings: (1) increased metabolism of arginine to citrulline, (2) increase of cGMP in the platelet/neutrophil system and (3) the inhibitory action of the L-arginine (L-Arg) competitive analogue, NG-nitro-L-arginine-methyl ester (L-NAME), which was reversed by L-Arg. Triflusal increased the stimulation of NO synthesis by neutrophils more than did of acetylsalicylic acid. The main metabolite of triflusal, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB), alone or in combination with acetylsalicylic acid, did not modify NO production by neutrophils. Therefore, the whole molecule of triflusal is needed to stimulate NO production by neutrophils. Our results show that, in the presence of neutrophils, triflusal exerts an antiplatelet effect greater than that of acetylsalicylic acid, demonstrating a more powerful stimulation of the NO/cGMP system. The present results indicate that it is possible to develop new and more potent acetylsalicylic acid-related antiplatelet drugs for the prevention of the myocardial ischemic/reperfusion processes.

Aspirin↗

Degree of hypercoagulability and hyperfibrinolysis is related to organ failure and prognosis after burn trauma.

Severely burned patients often present a hypercoagulability situation. However, its magnitude, time course, and relationship with organ failure and outcome remains to be established. Forty-three patients were studied on the first and seventh day after burn for hypercoagulability and fibrinolysis parameters. A hypercoagulability and hyperfibrinolysis state was found the first day after burn demonstrated by high levels of activated factor VII (VIIa, p<0.01), thrombin-antithrombin III complex (TAT, p<0.01), tissue plasminogen activator (t-PA, p<0.001) and D dimer (DD, p<0.01) and low levels of antithrombin III (ATIII, p<0.01), protein C (PC, p<0.01), plasminogen (PG, p<0.001) and alpha2 antiplasmin (AP, p<0.001). A paradoxical coexisting hypofibrinolysis was found as suggested by a low global fibrinolytic activity in the euglobulin plasma fraction fibrin plate assay (FA, p<0.01) and high levels of tissue plasminogen activator inhibitor type 1 (PAI-1, p<0.01). On day 7, a less marked hypercoagulability situation was found, with low ATIII (p<0.01) and PC (p<0.01), persisting the hypofibrinolytic situation observed on the first day. Non-survivors (NS) showed higher levels of VIIa (p<0.01), TAT (p<0.05) and t-PA (p<0.05), and lower levels of ATIII (p<0.05), PC (p<0.05) and AP (p<0.001) than survivors (S) on the first day. Also, there was a positive correlation of Marshall organ failure score with ATIII, (r2=0.49, p<0.001), PC, (r2=0.14, p<0.045) and PG levels, (r2=0.41, p<0.0003). Severely burned patients show a state of transient disseminated intravascular coagulation, related to the development of organ failure and outcome.

Adult↗

Weaning from mechanical ventilation in pediatric intensive care patients.

OBJECTIVE: The development of weaning predictors in mechanically ventilated children has not been sufficiently investigated. The purpose of this study was to evaluate the accuracy of some weaning indices in predicting weaning failure. DESIGN: Prospective, interventional study. SETTING: University-affiliated children's hospital with a 19-bed intensive care unit. PATIENTS: 84 consecutive infants and children requiring mechanical ventilation for at least 48 h and judged ready to wean by their primary physicians. INTERVENTIONS: Patients who met the criteria to start weaning underwent a trial of spontaneous breathing lasting up to 2 h. Bedside measurements of respiratory function were obtained immediately before discontinuation of mechanical ventilation and within the first 5 min of spontaneous breathing. The primary physicians were blinded to those measurements, and the decision to extubate a patient at the end of the spontaneous breathing trial or reinstitute mechanical ventilation was made by them. Failure to wean was defined as the requirement for mechanical ventilation at any time during the trial of spontaneous breathing (trial failure) or needing reintubation within 48 h of extubation (extubation failure). MEASUREMENTS AND MAIN RESULTS: Seventy-five patients had neither signs of respiratory distress nor deterioration in gas exchange during the trial and were extubated. Twelve patients required reintubation within 48 h. In 9 patients, mechanical ventilation was reinstituted after a median duration of the spontaneous breathing trial of 35 min. The only independent predictor of trial failure was tidal volume indexed to body weight [odds ratio 2.60, 95 % confidence interval (CI) 1.40 to 24.9]. The only independent predictor of extubation failure was frequency-to-tidal volume ratio indexed to body weight (odds ratio 1.23, 95 % CI 1.11 to 1.36). The sensitivity, specificity, and positive and negative predictive values to predict weaning failure were calculated for each of the above variables. These values were 0.48, 0.86, 0.53, and 0.83, respectively, for a frequency-to-tidal volume ratio higher than 11 breaths/min per ml per kg and 0.43, 0.94, 0.69, and 0.83, respectively, for a tidal volume lower than 4 ml/kg. CONCLUSIONS: Three-quarters of ventilated children can be successfully weaned after a trial of spontaneous breathing lasting 2 h. Both tidal volume and frequency-to-tidal volume ratio indexed to body weight were poor predictors of weaning failure in the study population.

Body Weight↗

[Palpebral ptosis and blepharospasm secondary to hemispheric cerebral infarction].

A case that combines cerebral eyelid ptosis and blepharospasm secondary to cerebral hemisphere infarction is shown. EMG recording from the facial and eyelid muscles revealed lack of the levator palpebrae superioris, orbicularis oculi and corrugator muscles activity. Any voluntary opening attempt lead to a simultaneous contraction of the three muscles. Blink reflex responses were normal although showed facilitation features on the right side and mild inhibition characteristics from the left side. Median nerve SEP revealed a loss of precentral components (P22-N30) as well as a delay and amplitude decrease of N20. Transcranial magnetic stimulation disclosed a complete lesion of corticospinal pathway for right upper limb. In this case, a right hemisphere lesion caused an unusual eyelid motor abnormality: cerebral eyelid ptosis and blepharospasm induced by the voluntary eyelid opening.

Aged↗

[Lateral femoral cutaneous neuropathy: paresthetic meralgia. Neurophysiological diagnosis].

INTRODUCTION: The neurophysiological approach to meralgia paresthetica (MP) deals with the possible abnormalities demonstrated in the peripheral nerve conduction and/or somatosensory evoked potentials (SEP) of the lateral femoral cutaneous nerve (LFCN). MATERIAL AND METHODS: To ascertain the diagnostic value of these methods, a group of 23 patients with unilateral MP symptoms has been studied; SEP of LFCN was also evaluated in a series of normal people. RESULTS: LFCN conduction was abnormal on the symptomatic side in 47.6% of the cases and nerve potential was absent on both sides in all the rest. SEPLFCN showed some impairment in 91% of the cases on the symptomatic side and responses were obtained on the asymptomatic side in every case; the most common abnormality was the delay of the response followed by its followed by its absence. In the normal group, the amplitude of potentials registered on the contralateral scalp to the stimulated side was usually higher than that registered on the median line, where they eventually lacked. Methodologically, this fact supports the need of a multiple recording of the SEPLFCN on the scalp. CONCLUSIONS: The SEPLFCN should be considered as the main technique for the objective diagnosis of MP and although LFCN conduction can supply useful information in individual cases, its exclusive use may lead to rather many positive false results.

Evoked Potentials, Somatosensory↗

Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. The Spanish Lung Failure Collaborative Group.

A 2-h T-tube trial of spontaneous breathing was used in selecting patients ready for extubation and discontinuation of mechanical ventilation. However, some doubt remains as to whether it is the most appropriate method of performing a spontaneous breathing trial. We carried out a prospective, randomized, multicenter study involving patients who had received mechanical ventilation for more than 48 h and who were considered by their physicians to be ready for weaning according to clinical criteria and standard weaning parameters. Patients were randomly assigned to undergo a 2-h trial of spontaneous breathing in one of two ways: with a T-tube system or with pressure support ventilation of 7 cm H2O. If a patient had signs of poor tolerance at any time during the trial, mechanical ventilation was reinstituted. Patients without these features at the end of the trial were extubated. Of the 246 patients assigned to the T-tube group, 192 successfully completed the trial and were extubated; 36 of them required reintubation. Of the 238 patients in the group receiving pressure support ventilation, 205 were extubated and 38 of them required reintubation. The percentage of patients who remained extubated after 48 h was not different between the two groups (63% T-tube, 70% pressure support ventilation, p = 0.14). The percentage of patients falling the trial was significantly higher when the T-tube was used (22 versus 14%, p = 0.03). Clinical evolution during the trial was not different in patients reintubated and successfully extubated. ICU mortality among reintubated patients was significantly higher than in successfully extubated patients (27 versus 2.6%, p < 0.001). Spontaneous breathing trials with pressure support or T-tube are suitable methods for successful discontinuation of ventilator support in patients without problems to resume spontaneous breathing.

Aged↗

Abnormalities in the metabolism of acetaminophen in patients infected with the human immunodeficiency virus (HIV).

The urinary concentration of acetaminophen and its glucuronide, sulphate, cysteine, and mercapturate conjugates was measured by high-performance liquid chromatography in 32 healthy volunteers, 9 untreated symptom-free HIV-seropositive subjects, and 19 patients with AIDS after a single oral dose of 1.5 g of acetaminophen. The concentration of the glucuronide conjugate was significantly lower in AIDS patients when simultaneously compared with concentrations found in healthy individuals and symptoms-free HIV-seropositive subjects. Differences between healthy volunteers and symptom-free HIV seropositives were not encountered. By contrast, urinary concentrations of sulphate and oxidation pathway-derived metabolites were significantly higher in AIDS patients as compared with the other two groups. When AIDS patients treated with zidovudine were compared with those not given this medication, differences in the urinary excretion of acetaminophen and its metabolites were not observed. However, the urinary concentration of mercapturic acid was significantly higher in those given enzyme inducers, such as rifampicin or phenytoin, than in AIDS patients not treated with these drugs. In summary, patients with advanced HIV infection showed reduced acetaminophen glucuronidation and increased formation of the hepatotoxic oxidation metabolites, which was independent of zidovudine therapy.

Acetaminophen↗

Selective allergic reaction to oral cloxacillin.

BACKGROUND: Previous observations indicate that in some instances subjects allergic to penicillins may experience an allergic reaction after taking the drug by one route but have good tolerance after being administered the same drug by a different route. OBJECTIVE: The purpose was to establish if cloxacillin (CLX) induced a selective response only after oral route administration in a suspected case and to study if there were differences between the oral and parenteral formulations. METHODS: Skin tests were carried out using benzylpenicillin (BP) conjugated to poly-L-lysine (BPO-PLL), minor determinant mixture of benzylpenicillin (MDM), ampicillin (AMP), amoxicillin (AX) and cloxacillin (CLX). Radioallergosorbent assay (RAST) was carried out using BPO-PLL, AX-PLL and CLX-PLL sensitized discs. In the case the skin tests and RAST were negative, a controlled challenge administering the drug by both oral and parenteral route was made. Urine samples were taken at prechallenge (basal levels) and at three periods after challenge (1-3, 3-6 and 6-9 h). Analysis of oral and parenteral formulations was made by HPLC chromatography. RESULTS: All skin tests and RASTs were negative. With the challenge tests the patient tolerated parenteral BP and oral phenoxymethyl penicillin (PV) and oral and parenteral AMP up to therapeutic concentrations. Parenteral CLX (500 mg) was also tolerated but 30 min after administering 50 mg by the oral route progressive generalized erythema with pruritus, facial angioedema and tachycardia developed. Urine samples taken during the challenge tests showed an increased excretion of N-methyl histamine (N-MH) 3 h after challenge with oral CLX but no change in N-MH levels after challenge with parenteral CLX or the other penicillins, indicating that histamine was released during the allergic episode with oral CLX. HPLC analysis of the oral and parenteral CLX formulations indicated that there were no differences and that neither polymers no other contaminant materials were present. CONCLUSION: Although the nature of the allergenic determinant involved in the induction of the reaction is not yet known, the oral route may have favoured the production of a metabolite not generated by the parenteral route.

Administration, Oral↗

Effects of aspirin on platelet-neutrophil interactions. Role of nitric oxide and endothelin-1.

BACKGROUND: In recent studies, the hypothesis has been raised that the mechanisms by which aspirin acts as a protective anti-ischemic agent exceed the inhibition of platelet thromboxane A2 synthesis. Recently, new data have been obtained disclosing a platelet-antiaggregating effect by neutrophils, which occurs through a nitric oxide (NO)/cGMP-dependent pathway. METHODS AND RESULTS: The present study, using platelets and neutrophils from normal subjects, was undertaken to assess the putative effect of aspirin on the neutrophil-mediated, platelet-inactivating effect. Aspirin facilitated the inhibitory effect of neutrophils on platelet activation by thrombin, ADP, or epinephrine. This effect was equally evident in vitro and in blood samples of normal individuals taking aspirin. A significant stimulation of NO-mediated mechanisms in the presence of aspirin was disclosed by different methods, as follows: (1) the increased metabolism of arginine to citrulline, (2) the increase of cGMP in the platelet/neutrophil system, and (3) the inhibitory action of the L-arginine (L-Arg)-competitive analogue L-NMMA, which was reversed by L-Arg. The effect of aspirin appeared to be related to cyclooxygenase inhibition, since it was reproduced by using indomethacin. The vasoconstricting peptide endothelin-1 (ET-1) reversed the effect of aspirin through the endogenous production of platelet-activating factor (PAF) by neutrophils, as judged by the marked inhibitory effect of the PAF antagonist BN-52021. CONCLUSIONS: Our results show that a significant part of the effect of aspirin on platelet activation involves a neutrophil-mediated, NO/cGMP-dependent mechanism. The presence of ET-1 counterbalances these effects of neutrophils on platelet activation, therefore acting as an indirect proactivating agent. These results add new elements for interpreting the effects of aspirin on the interactions between blood cells, with special reference to high endothelin states (for example, ischemia/reperfusion processes).

Animals↗

A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group.

BACKGROUND: Weaning patients from mechanical ventilation is an important problem in intensive care units. Weaning is usually conducted in an empirical manner, and a standardized approach has not been developed. METHODS: We carried out a prospective, randomized, multicenter study involving 546 patients who had received mechanical ventilation for a mean (+/- SD) of 7.5 +/- 6.1 days and who were considered by their physicians to be ready for weaning. One hundred thirty patients had respiratory distress during a two-hour trial of spontaneous breathing. These patients were randomly assigned to undergo one of four weaning techniques: intermittent mandatory ventilation, in which the ventilator rate was initially set at a mean (+/- SD) of 10.0 +/- 2.2 breaths per minute and then decreased, if possible, at least twice a day, usually by 2 to 4 breaths per minute (29 patients); pressure-support ventilation, in which pressure support was initially set at 18.0 +/- 6.1 cm of water and then reduced, if possible, by 2 to 4 cm of water at least twice a day (37 patients); intermittent trials of spontaneous breathing, conducted two or more times a day if possible (33 patients); or a once-daily trail of spontaneous breathing (31 patients). Standardized protocols were followed for each technique. RESULTS: The median duration of weaning was 5 days for intermittent mandatory ventilation (first quartile, 3 days; third quartile, 11 days), 4 days for pressure-support ventilation (2 and 12 days, respectively), 3 days for intermittent (multiple) trials of spontaneous breathing (2 and 6 days, respectively), and 3 days for a once-daily trial of spontaneous breathing (1 and 6 days, respectively). After adjustment for other covariates, the rate of successful weaning was higher with a once-daily trial of spontaneous breathing than with intermittent mandatory ventilation (rate ratio, 2.83; 95 percent confidence interval, 1.36 to 5.89; P < 0.006) or pressure-support ventilation (rate ratio, 2.05; 95 percent confidence interval, 1.04 to 4.04; P < 0.04). There was no significant difference in the rate of success between once-daily trials and multiple trials of spontaneous breathing. CONCLUSIONS: A once-daily trial of spontaneous breathing led to extubation about three times more quickly than intermittent mandatory ventilation and about twice as quickly as pressure-support ventilation. Multiple daily trials of spontaneous breathing were equally successful.

Acute Disease↗

Protective effect of diltiazem against acetaminophen hepatotoxicity in mice.

There is evidence that an increase in cytosolic Ca++ concentration is a terminal event in the progression to cell death in toxic liver injury. We have compared the hepatoprotective effects of N-acetylcysteine (1 g/kg) and the calcium channel blocking agent, diltiazem (24 mg/kg), when given at 30 min, 3 h and 6 h after single intraperitoneal overdoses of acetaminophen (500 mg/kg) in mice. Overall beneficial effects on mortality, liver necrosis score, and plasma alanine aminotransferase (ALT) activity were found in diltiazem-treated mice 24 h after acetaminophen overdose. However, the most marked effects were obtained when diltiazem was given 6 h after acetaminophen. N-acetylcysteine was more effective than diltiazem at 30 min and 3 h, although it was less effective at 6 h. Mean plasma concentrations of the mercapturate metabolite (hepatic oxidative metabolism) were not significantly different among animals receiving acetaminophen alone or in combination with diltiazem, which suggests that the hepatoprotective effects of diltiazem are not exerted by inhibition of drug metabolic enzymes.

Acetaminophen↗

[Dermatomal somatosensory evoked potentials in the diagnosis of focal lesions of the spinal cord].

We studied 13 patients suffering from localized spinal cord lesions by means of somatosensory evoked potentials obtained by electrical stimulation at various dermatome levels (SEPD). The results were compared to those of somatosensory evoked potentials obtained by stimulation of the posterior tibial nerve (SEPpt), as well as to clinical and radiologic data. Structural lesions could be demonstrated in 8 patients; in 5 patients, however, X-rays were normal and/or incompatible with symptoms. We found clear correlations among clinical or radiologic data and the level of lesion indicated by SEPD in all 13 patients. In one case SEPD were abnormal 6 months in advance of the first alteration in magnetic resonance imaging. Abnormal SEPD and SEPpt results were consistent, suggesting the existence of a common central pathway to carry stimuli. SEPD should be considered a useful, reliable technique for assessing spinal cord function, especially when no structural lesion can be demonstrated or when spinal injury is doubtful or when several segments are involved.

Adolescent↗

[Plasma levels of alanine aminotransferase in experimental liver necrosis induced by overdosage of paracetamol in mice].

OBJECTIVE: To investigate the correlation between the hepatocellular damage and ALT plasma level after paracetamol overdosage in mice. EXPERIMENTAL DESIGN: A total of 30 female, 16 week-old mice (Souris OF1 strain), weighing 25-30 g were used. After 18 hours fast period, single doses of 500 mg/kg of paracetamol were administered intraperitoneally. The animals were killed by decapitation 24 hours after paracetamol injection, fasting being continued, although free access to water was allowed. ALT plasma levels were determined. The hepatocellular damage was graded from 0-4 (+). Plasma levels of mercapturate conjugate were measured by HPLC. RESULTS: The study showed a statistically significant correlation (r = 0.8, p = 0.00001) between ALT plasma levels and the degree of hepatocellular damage but not with concentrations of mercapturate conjugate. CONCLUSIONS: These findings suggest that ALT plasma levels give a reliable indication of the severity of hepatic necrosis, after experimental paracetamol overdosage in mice.

Acetaminophen↗