PubMed Health⌕ Search

Biomedical subjects

G Rodrigo

Publications and source records attributed to G Rodrigo.

At least 19 recordsLinked to original sources
PubMed2000

Efficacy of magnesium sulfate in acute adult asthma: a meta-analysis of randomized trials.

The purpose of this article was to review of the literature to determine whether MgSO4 provides an additive improvement in adults with acute asthma in the emergency department (ED). English-language published and unpublished studies (1968-1998) were retrieved using MEDLINE, SCIENCE CITATION INDEX, CURRENT CONTENTS, bibliographic reviews of primary research, review articles, consultation with experts, and the register of Medical Editors' Trial Amnesty. Meta-analysis of randomized, placebo controlled trials. The five selected trials included 374 patients with acute asthma (mean age 38.3 +/- 13.4 years, 30% men, 70% women). The main outcome measure was pulmonary function; admission rate was evaluated as a secondary goal. Individual and pooled effect sizes (ES) were determined for pulmonary function data. Binary outcome (admission rate) was combined and reported as odds ratio (OR). The overall summary ES (95% confidence interval [CI]) of the five trials satisfying all inclusion criteria, weighted by sample size was nonsignificant (ES = 0.02, -0.20 to 0.24, P = .84). This pooled ES was equivalent to 1.7%, 95% CI: -9.8 to 13.1%) greater in pulmonary function the MgSO4 compared with the control group. On the other hand, four studies addressed the effect of MgSO4 administration on hospital admissions. Pooled results revealed that MgSO4 did not decrease significantly admission rates (OR = 0.68, 95% CI: 0.41 to 1.15). The existing evidence reveals that the addition of MgSO4 to ED patients with moderate to severe asthmatic exacerbations does not alter treatment outcomes. Nevertheless, the number and size of studies being pooled remain small.

Acute Disease↗
PubMed2000

DNA replication but not nucleotide excision repair is required for UVC-induced replication protein A phosphorylation in mammalian cells.

Exposure of mammalian cells to short-wavelength light (UVC) triggers a global response which can either counteract the deleterious effect of DNA damage by enabling DNA repair or lead to apoptosis. Several stress-activated protein kinases participate in this response, making phosphorylation a strong candidate for being involved in regulating the cellular damage response. One factor that is phosphorylated in a UVC-dependent manner is the 32-kDa subunit of the single-stranded DNA-binding replication protein A (RPA32). RPA is required for major cellular processes like DNA replication, and removal of DNA damage by nucleotide excision repair (NER). In this study we examined the signal which triggers RPA32 hyperphosphorylation following UVC irradiation in human cells. Hyperphosphorylation of RPA was observed in cells from patients with either NER or transcription-coupled repair (TCR) deficiency (A, C, and G complementation groups of xeroderma pigmentosum and A and B groups of Cockayne syndrome, respectively). This exclude both NER intermediates and TCR as essential signals for RPA hyperphosphorylation. However, we have observed that UV-sensitive cells deficient in NER and TCR require lower doses of UV irradiation to induce RPA32 hyperphosphorylation than normal cells, indicating that persistent unrepaired lesions contribute to RPA phosphorylation. Finally, the results of UVC irradiation experiments on nonreplicating cells and S-phase-synchronized cells emphasize a major role for DNA replication arrest in the presence of UVC lesions in RPA UVC-induced hyperphosphorylation in mammalian cells.

Cell Line, Transformed↗
PubMed1999

A meta-analysis of the effects of ipratropium bromide in adults with acute asthma.

PURPOSE: To review the literature to determine whether inhaled ipratropium bromide provides additive benefits to adults with acute asthma who are being treated with beta-agonists in an emergency department. SUBJECTS AND METHODS: English-language studies, both published (1978 to 1999) and unpublished, were retrieved using Medline, Science Citation Index, Current Contents, bibliographic reviews of primary research, review articles, consultation with experts, and the register of Medical Editors' Trial Amnesty. Only randomized, double-blind, controlled trials that enrolled patients having an exacerbation of asthma were included. The main outcome measure was pulmonary function; hospital admission rate was also evaluated. RESULTS: Ten studies including 1,483 adults with acute asthma were selected (mean age 32 +/- 13 years, 36% men). The overall effect size in SD units of pulmonary function showed a significant benefit from ipratropium (effect size 0.14, 95% confidence interval [CI]: 0.04 to 0.24, P = 0.008). Study-specific effect sizes ranged from 0.03 to 0.63. This pooled effect size was equivalent to a 10% (95% CI: 2% to 18%) increase in forced expiratory volume in 1 second (FEV1) or peak expiratory flow in the ipratropium group compared with the control group. Analysis of the four studies that included patients with extreme obstruction (FEV1 or peak flow <35% of predicted at presentation) showed substantial improvement with ipratropium therapy (effect size 0.38, 95% CI: 0.09 to 0.67). In the five trials (1,186 patients) that studied the effect of ipratropium administration on hospital admissions, pooled results revealed that ipratropium reduced admission rates significantly (odds ratio 0.62, 95% CI: 0.44 to 0.88, P = 0.007). CONCLUSIONS: The addition of ipratropium to beta-agonist therapy offers a statistically significant, albeit modest, improvement in pulmonary function, as well as a reduction in the rate of hospital admissions.

Acute Disease↗
PubMed1999

Subarachnoid hemorrhage following permissive hypercapnia in a patient with severe acute asthma.

In this article, we describe a case of a subarachnoid hemorrhage (SAH) in an acute severe asthma patient following mechanical hypoventilation. A 49-year-old man was admitted to an Intensive Care Unit with an acute exacerbation of asthma. After 3 days of mechanical ventilation (hypercapnia and normoxaemia), it was noted that his right pupil was fixed, dilated, and unreactive to light. Computed tomography (CT) scan showed localized SAH within the basilar cisterns and diffuse cerebral swelling. On the fourth day, a new CT scan showed hemorrhage resorption and a cerebral swelling decrease. In the following days, the patient's condition continued improving with no detectable neurological deficits. A review of similar published reports showed that all patients performed respiratory acidosis, normoxaemia, and hypercapnia. The most frequent neurological sign was mydriasis, and all subjects showed cerebral edema. Since normoxaemic hypercapnia has been associated with absence, or less cerebral edema, we considered additional factors to explain cerebral edema and intracranial hypertension causes. Thus, intrathoracic pressures due to patient's efforts by forcibly exhaling, or during mechanical ventilation, would further increase intracranial pressure by limiting cerebral venous drainage. This case emphasizes the fact that patients with acute severe asthma who have developed profoundly hypercarbic without hypoxia before or during mechanical ventilation, may have raised critical intracranial pressure.

Acute Disease↗
PubMed1999

Corticosteroids in the emergency department therapy of acute adult asthma: an evidence-based evaluation.

OBJECTIVE: To review the literature to determine the benefits of corticosteroids (CCSs) (oral, IM, IV, or inhaled) in the treatment of adult patients with acute asthma presenting at an acute-care setting. SEARCH STRATEGY: A MEDLINE search was conducted using the following terms: (1) Asthma OR Wheez, AND (2) Glucocorticoids OR Steroids, AND (3) Acute OR Emerg. Other sources were the CURRENT CONTENTS database, review articles, reference sections of located studies, and a manual search of the top 15 journals for respiratory and emergency medicine. SELECTION CRITERIA: Patients were selected for the study by the following criteria: (1) English language; (2) adult patients with asthma whose acute exacerbations were the primary reason for assessment; (3) involvement in randomized, controlled trials conducted in an emergency care setting; (4) patients had participated in a study investigating a primary research question involving treatment with CCSs; and (5) outcomes based on results of pulmonary function tests and on hospital admission rates. RESULTS: At the 3-h assessment, only high doses of inhaled CCSs significantly improved pulmonary function compared with placebo (effect size [ES], 0.56; 95% confidence interval [CI], 0.15 to 0.97). On the other hand, after receiving IV CCSs, patients required at least 6 to 24 h to show moderate but nonsignificant improvements of pulmonary function (6-h ES, 0.44 [95% CI, -0.01 to 0.89]; 12-h ES, 0.54 [95% CI, -0.08 to 1.17]; and 24-h ES, 0.53 [95% CI, -0.39 to 1.45]). The data from the six studies that we used to pool information on admission rate outcome showed a 32% reduction in favor of the use of IV CCSs (relative risk [RR], 0.68 [95% CI, 0.47 to 0.99]; number needed to treat, 12.5 [95% CI, 7.1 to 50]). However, the pooled effect of the three high-quality studies showed no difference between groups (RR, 1.21; 95% CI, 0.67 to 2.18). Oral CCSs provided a similarly beneficial effect on pulmonary function when compared with parenteral administration (ES, -0.14; 95% CI, -0.82 to 0.31. Finally, the results showed a nonsignificant favorable trend toward improved outcome with medium or high doses of CCSs. CONCLUSIONS: This evidence-based evaluation suggests that the administration of parenteral CCSs to the patient on arrival at the emergency department (ED) neither improves airflow obstruction nor reduces the need for hospitalization. Parenteral CCSs probably require >6 to 24 h to begin to act. Comprehensible conclusions about admission rates in the ED setting are difficult to make. At the 3-h assessment, only high doses of inhaled CCSs (in one study) significantly improved pulmonary function compared with placebo. IV and oral CCSs appear to have equivalent effects, and there is a tendency toward improvement in pulmonary function with medium or high doses.

Adult↗
PubMed1999

[DNA-dependent protein kinase: a major protein involved in the cellular response to ionizing radiation].

DNA-dependent protein kinase (DNA-PK) is a DNA-activated nuclear serine/threonine protein kinase. DNA-PK consists of a regulatory sub-unit, the heterodimeric Ku protein (composed of a 70- and a 86-kDa subunit) which binds DNA ends and targets the catalytic sub-unit, DNA-PKcs to DNA strand breaks. DNA-PK plays a major role in the repair of double-strand breaks induced in DNA after exposure to ionizing radiation as shown by the extreme radiosensitivity of cells with mutations in Ku86, Ku70 or DNA-PKcs genes. Cells deficient in DNA-PK activity also exhibit hypersensitivity to genotoxic drugs such as cisplatin and nitrogen mustards. In the first part of this review, the current knowledge on the biochemical characteristics of DNA-PK, its mechanism of action in DNA repair and the phenotype of DNA-PK deficient cells is summarized. These results suggest that DNA-PK might play a role in the acquisition of a resistant phenotype of human tumors to radiotherapy, chemotherapy using genotoxic drugs or to both treatments. In the second part of this review, the studies devoted to inhibition of DNA-PK in order to enhance cancer therapy by DNA-damaging agents are presented.

DNA Damage↗
PubMed1998

Salbutamol treatment of acute severe asthma in the ED: MDI versus hand-held nebulizer.

The objectives of this study were to compare the efficacy of salbutamol delivered by either metered-dose inhaler plus spacer (MDI-spacer) or by wet nebulization (NEB), and to determine the relationships between physiologic responses and plasma salbutamol concentrations. Asthmatic patients presenting to the emergency department (ED) with acute severe asthma (forced expiratory volume in the first second [FEV1] less than 50% of predicted) were enrolled in a randomized, double-blind, parallel-group study. The MDI-spacer group received salbutamol, delivered via MDI into a spacer device, in four puffs actuated in rapid succession at 10-minute intervals (2.4 mg/h). The NEB group was treated with nebulized salbutamol, 1.5 mg, via nebulizer at 15-minute intervals (6 mg/h). Doses were calculated on the basis of the percentage of total dose that reaches the lower airway with both methods. The protocol involved 3 hours of this treatment. Mean peak expiratory flow rate (PEFR) and FEV1 improved significantly over baseline values for both groups (P=.01). However, there were no significant differences between both groups for PEFR and FEV1 at any point studied. The examination of the relationships between cumulative dose of salbutamol and change in FEV1 showed a significant linear relationship (P=.01) for both methods (MDI r=.97; NEB r=.97). The regression equations showed that for every 1 mg of salbutamol by MDI-spacer, 2.5 mg are needed from nebulization to have equal therapeutic response. At the end of treatment, the salbutamol plasma levels were 10.1+/-1.6 ng/ml for the MDI-spacer group and 14.4+/-2.3 ng/ml for the NEB group (P=.0003). Both groups showed a nonsignificant heart rate decrease. A significant group-by-time interaction means that differences between groups increased with time (P=.04). Additionally, the NEB group presented a higher incidence of tremor (P=.03) and anxiety (P=.04), reflecting larger systemic absorption of salbutamol. These data indicate that when doses used are calculated on the basis of the percentage of total drug that reaches the lower airway, there was equivalent bronchodilatation after salbutamol administered by either MDI-spacer or nebulization in patients with acute severe asthma. However, nebulizer therapy produced greater side effects related to the increase in salbutamol absorption and higher plasma level.

Acute Disease↗
PubMed1998

Inhaled flunisolide for acute severe asthma.

This randomized, double-blind trial was designed to determine the benefit of high and cumulative doses of flunisolide added to salbutamol in patients with acute asthma in the emergency room (ER). Ninety-four patients who presented to an ER for treatment of an acute exacerbation of asthma were assigned in a randomized, double-blind fashion to receive salbutamol and placebo (n = 47) or salbutamol combined with flunisolide (n = 47). Both drugs were administered successively through a metered-dose inhaler and spacer at 10-min intervals for 3 h (400 microg of salbutamol and 1 mg of flunisolide every 10 min). In both groups, FEV1 and peak expiratory flow rate (PEFR) improved significantly over baseline values (p < 0.01). Results in the flunisolide group were significantly different from those in the placebo group at 90, 120, 150, and 180 min. Data analyzed separately in accord with the duration of the attack before presenting at the ER (< 24 or > or = 24 h) showed that the placebo > or = 24 h group produced a significantly lower FEV1 at 120, 150, and 180 min (p = 0.041) than did the remaining groups. Our data support the theory that high and cumulative doses of inhaled flunisolide administered by metered-dose inhaler with spacer and added to salbutamol are an effective therapy for patients with acute asthma and a prolonged duration of symptoms before ER presentation.

Acute Disease↗
PubMed1998

Therapeutic response patterns to high and cumulative doses of salbutamol in acute severe asthma.

STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses of salbutamol and to determine the factors that contribute to outcome in acute severe asthma. SETTING: The emergency department (ED) of a large, urban hospital with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred sixteen consecutive patients with acute exacerbations of asthma were enrolled in the trial, using a prospective sequential design. INTERVENTIONS: All patients were treated with salbutamol delivered with a metered-dose inhaler into a spacer device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose-response increase in pulmonary function was found, but only 70% improved sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the drug within 1 h to reach the discharge threshold, whereas the remainder 30% need > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were characterized by a more severe disease as judged by previous beta2-agonist use, larger duration of attack before ED visit, and a more severe obstruction at presentation. However, the most important predictors of outcome were peak expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute, and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study described two different therapeutic response patterns to salbutamol. Almost 70% of patients were sensitive to salbutamol (good response pattern), and in this group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of patients (poor response pattern), salbutamol in high doses had little effect. However, the outcome was not determined by the intensity of the initial symptoms or by the value of the presenting PEFR, but rather by the early (30 min) short-term response to treatment.

Acute Disease↗
PubMed1998

Early prediction of poor response in acute asthma patients in the emergency department.

STUDY OBJECTIVES: The aim of this study was to develop an acute asthma index for utilization in the early differentiation between patients with poor and good therapeutic response in the emergency department (ED) setting. SETTING: The ED of a large tertiary-care hospital in Montevideo, Uruguay. PATIENTS AND DESIGN: The study included 145 consecutive adult patients (mean age [+/- SEM], 33.4+/-0.97) who presented to an ED (analysis sample). The inclusion criteria were: (1) age between 18 and 50 years; (2) a peak expiratory flow rate (PEFR) or FEV1 below 35% of predicted; and (3) no history of chronic cough or cardiac, hepatic, renal, or other medical disease. INTERVENTIONS: All patients were treated with salbutamol delivered by metered-dose inhaler into a spacer device in four puffs actuated at 10-min intervals. The protocol involved 3 h of this treatment. After that time, patients with poor response received hydrocortisone, 500 mg IV. The outcome was defined as the FEV1 after 3 h of treatment in a dichotomized form: < or =45% of predicted = poor response, and >45% of predicted = good response. RESULTS: Biserial correlations between different variables and the outcome showed that PEFR as percent of predicted and PEFR variation over baseline, both measured at 30 min, were the most important predictors of a good or poor response after 3 h of treatment. Next, we developed an acute asthma index using these predictive measures. A comparison of index sensitivity, specificity, predictive values, and the area under the receiver operating characteristic (ROC) curve across different cutoff scores indicates that a score of 4 results in the least error of classification (sensitivity = 0.79; specificity = 0.96; area under the ROC curve = 0.87; positive predictive value = 0.94; and negative predictive value = 0.86). To validate the developed index, we prospectively studied a second sample of 77 consecutive patients (mean age 32.6+/-1.22 years) who presented for treatment of acute asthma (validation sample). The area under the ROC for the analysis sample was not greater than the validation sample area (p = 0.24). Thus, the validation sample showed similar levels of sensitivity and specificity, positive and negative predictive values, and area under the ROC curve (0.80, 0.88, 0.85, 0.84, and 0.89, respectively), indicating the stability of the model. CONCLUSIONS: The study suggested the predictive accuracy of a two-item bedside index. This acute asthma index provides a tool for assessing acute asthma severity using objective criteria easily accessible to the ED physician.

Acute Disease↗
PubMed1997

A new index for early prediction of hospitalization in patients with acute asthma.

Data from studies using the factor analysis technique have shown that asthma appears to be multidimensional and that most of the subjective and objective measures utilized in the assessment of asthma patients represent a much smaller number of underlying dimensions. Additionally, several investigators have emphasized that evaluation of acute asthma is an ongoing process, as the degree and time course of the response to therapy vary considerably between patients. The aim of this study was to examine the usefulness of the most common clinical and objective measures in the evaluation of acute asthma in the emergency department (ED) for predicting the outcome of acute episodes in adults. In an effort to identify variables that can predict the outcome of patients with acute asthma, 184 adults (age 32.4 +/- 11.6 [mean +/- SD]) (analysis sample) who presented to an ED were studied. The inclusion criteria were: (1) age between 18 and 50 years; (2) a peak expiratory flow rate (PEFR) or forced expiratory volume in the first second (FEV1) below 50% of predicted; and (3) no history of chronic cough or cardiac, hepatic, renal, or other medical disease. All patients were treated with salbutamol delivered with metered-dose inhaler (MDI) into a spacer device in 4 puffs actuated at 10-minute intervals and 500 mg of intravenous hydrocortisone. The multivariate statistical technique of discriminant analysis was utilized to develop the index, and after this, a new sample (n = 91), the validation sample, was studied to validate the index. In the analysis sample 163 patients (89%) were discharged (relapse rate within 7 days = 10%) and 21 (11%) were hospitalized (mean duration of hospital stay = 5.75 +/- 2.81 days). The discriminant analysis identified three independent variables that make the greatest contribution in discriminating between the two groups studied: PEFR variation over baseline, PEFR as percent of predicted, and accessory muscle use, all measured at 30 minutes after the beginning of treatment. A multifactorial index using these three variables presented a sensitivity of 0.86, a specificity of 0.96, a positive predictive value of 0.75, and a negative predictive value of 0.98. The validation sample index sensitivity, specificity, and positive and negative predictive values were 0.83, 0.97, 0.83, and 0.97, respectively. In conclusion, a predictive index has been developed for evaluating patients with asthma who present to an ED. This simple and brief three-item index can facilitate an early decision (30 minutes of treatment) to hospitalize patients with severe asthma.

Acute Disease↗
PubMed1997

Effect of age on bronchodilator response in acute severe asthma treatment.

STUDY OBJECTIVES: This study was designed to evaluate the effects of age on bronchodilator response to salbutamol in patients with acute severe asthma in the emergency department. SUBJECTS AND METHODS: Sixty-four sequential patients (mean age, 34.2+/-10.7 years) with acute asthma were enrolled in the trial. Using age as a major criterion, we divided the sample in two groups: the young one (age < or = 35 years, n=30) and the older (> 35 years, n=34). All patients were treated with salbutamol delivered with metered-dose inhaler into a spacer device, in a dose of four puffs every 10 min (100 microg per actuation) during 3 h. RESULTS: Mean FEV1 improved significantly over baseline values for both groups (p=0.001). At final disposition, the mean percent of predicted FEV1 was 55.1+/-16.3% in the young group and 58.0+/-20.9% in the older group. There were no significant differences between both groups for FEV1 percent response at any point studied. A significant increase in heart rate over baseline was seen in the older group (p=0.001). Older patients also presented a higher incidence in nausea and tremor. Young and older patients with acute asthma achieved equivalent bronchodilation response to salbutamol. CONCLUSIONS: We concluded that age is not a predictor of response to beta-agonists.

Acute Disease↗
PubMed1996

Metered dose inhaler salbutamol treatment of asthma in the ED: comparison of two doses with plasma levels.

Two cumulative doses of salbutamol delivered by metered dose inhaler (MDI) with a pear-shaped spacer were compared (400 micrograms vs 600 micrograms at 10-minute intervals). Twenty-two patients (mean age 35.1 +/- 11.1 years) with acute exacerbation of asthma were randomly selected, in a double-blind fashion, to receive salbutamol delivered with MDI into a spacer device in 4 puffs at 10- minute intervals (100 micrograms or 150 micrograms per actuation) during 3 hours (1200 micrograms or 1800 micrograms each 30 minutes). Mean peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1) improved significantly over baseline values for both groups (P < .001). Nevertheless, there were no significant differences between both groups for PEFR and FEV1 at any time point studied. A significant net reduction of heart rate was observed in the 400 microgram group (P < .01). On the other hand, a significant increase in heart rate was observed in the 600 microgram group (P < .001). The QTc interval did not show a significant prolongation, and the two groups presented moderate decreases of serum potassium levels. There was a significant dose-related increase (P = .027) in Sao2. Additionally, the 600 microgram group generated a serum glucose level increase from 0.85 +/- 0.12 mg/100 mL to 1.04 +/- 0.25 mg/100 mL (P = .02), with a higher incidence in 4 symptoms (tremor, headache, palpitations, and anxiety). These data support the notion that the treatment of acute asthma patients in the emergency department setting with salbutamol, 2.4 mg/h, delivered by MDI and spacer (4 puffs at 10-minute intervals) produces satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects. However, an increase of 50% of the dose (600 micrograms at 10-minute intervals) produced a nonsignificant, slightly better therapeutic response but with greater side effects, probably related to higher salbutamol levels.

Adrenergic beta-Agonists↗
PubMed1995

High-dose MDI salbutamol treatment of asthma in the ED.

Beta-adrenergics have long been under special scrutiny because of their potential for cardiotoxicity. To assess the safety of high doses of salbutamol delivered by metered dose inhaler (MDI) with spacer in the emergency department (ED) setting, 11 patients (mean age 33 +/- 12.2 years) with severe acute asthma were studied. All patients were treated with 400 micrograms of salbutamol at 10-minute intervals for 3 hours (1,200 micrograms each 30 minutes or 7,200 micrograms at 180 minutes. There were dose-related significant increases in forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) (P < .01), with a net mean increase of 90.4% and 80.1%, respectively. A significant (P < .01) reduction of heart rate was observed with treatment. At the end of protocol, reductions ranged from 7 beats/min to 35 beats/min (mean decrease 10.6 +/- 10.5 beats/min). There was no prolongation in the QTc interval. Mean baseline serum potassium was 4.23 +/- 0.53 mmol/L and decreased nonsignificantly after treatment to 3.99 +/- 0.62 mmol/L. Only 4 patients showed net decreases. There were no significant changes in oxygen saturation and plasma glucose. The mean end-treatment salbutamol level was 10.0 +/- 1.67 ng/mL. These data support the notion that treatment of acute asthma patients in the ED with 2.4 mg salbutamol per hour delivered by MDI and spacer produce satisfactory bronchodilation, low serum concentration, and minimal extrapulmonary effects.

Acute Disease↗