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Biomedical subjects

Mario H Vargas

Publications and source records attributed to Mario H Vargas.

14 recordsLinked to original sources

Evaluation of antihypoxemic maneuvers before tracheal aspiration in mechanically ventilated newborns.

Periodical tracheal aspiration in mechanically ventilated patients is necessary to remove mucus from the airways. In children and adults, this procedure causes transient hypoxemia, which may be prevented by hyperoxia and/or hyperventilation. These findings, however, have not been sufficiently assessed in newborn infants. Thus we investigated the usefulness of hyperoxia and/or hyperventilation as antihypoxemic maneuvers before tracheal aspiration in newborn infants. Our design was a prospective, randomized, multiple crossover study. The setting was the NICU of a third-level pediatric hospital in Mexico City. Patients included 15 newborn infants under mechanical ventilation. Within a 12-hr period, every patient received, in random order, three antihypoxemic maneuvers during 1 min just before tracheal aspiration: hyperoxia (10% increase of baseline FiO2), hyperventilation (50% increase of ventilator cycling rate), or both. Additionally, a control (sham) maneuver was also applied. Pulse oximeter saturation (SpO2) was recorded before and after each antihypoxemic maneuver, and at 0, 15, 30, 60, and 300 sec after tracheal aspiration. Basal values of SpO2 (81.5 +/- 1.5%) increased with all three antihypoxemic maneuvers (SpO2 over 90%, P <0.05 to P <0.01). Immediately after tracheal aspiration a drop in the SpO2 could be detected in all infants. However, patients receiving hyperoxia showed higher SpO2 values (87.1 +/- 1.8%) than those observed with the sham maneuver (76.9 +/- 2.3%, P <0.01). From this point on, all newborn infants in all conditions (even those with sham maneuver) had spontaneous increments of SpO2 that at 300 sec were again higher than their respective basal values (P <0.05 to P <0.0005). At this time, SpO2 values from following the hyperoxia maneuver were still higher than those following the sham maneuver (P <0.05). Our results show that, similar to what occurs at other ages, tracheal aspiration in mechanically ventilated newborn infants causes transient hypoxemia, which can be partially prevented by previous application of antihypoxemic maneuvers, especially hyperoxia.

Cross-Over Studies↗

Underestimation of the peak flow variability in asthmatic children: evaluation of a new formula.

Asthma guidelines suggest evaluation of peak expiratory flow (PEF) variability, but timing for the two PEF measurements is not mentioned. Usual formula calculates amplitude as percentage of mean day-night PEF values. Since PEF circadian changes follow a sinusoidal function, we reasoned that variability might be calculated by measuring PEF at 4 pm (PEF(1)) and either at 10 am or 10 pm (PEF(2)) with the formula %variability = 200 . |PEF(1)-PEF(2)|/PEF(2). Children with stable, mild intermittent asthma were recruited from an Asthma Clinic and asked to perform PEF measurements at even hours during a week, until 12 measurements covering a 24-h period were accomplished. From these measurements we calculated PEF variability through several methods. Accuracy of such methods to predict actual PEF variability was assessed through the concordance correlation coefficient (r(c)). Thirty five asthmatic children were recruited. Actual PEF variability, calculated with the usual formula using the highest and lowest PEF obtained at any time of the 24 h cycle had a median of 37.3% (range, 0-88.5%). Variability calculated through other methods was: usual formula with highest and lowest PEF obtained from the sinusoidal curve, 21.4% (r(c) = 0.79); usual formula with PEF measured at 4 pm and 4 am, 17.8% (r(c) = 0.67); proposed formula using PEF measured at 4 pm and either 10 pm, 15.9% (r(c) = 0.68), or 10 am, 17.4% (r(c) = 0.69). Some examples with PEF measured in the morning (8 am or 10 am) and at night (8 pm or 10 pm) yielded median PEF variability from 4.0% (r(c) = 0.18) to 8.7% (r(c) = 0.38). Current methods for calculating PEF variability seemed not to be accurate enough as to be confident, suggesting that an in-deep reevaluation of the usefulness of PEF variability or, conversely, of the methods to assess it, should be done.

Adolescent↗

A cholesterol-rich diet accelerates bacteriologic sterilization in pulmonary tuberculosis.

BACKGROUND: Hypocholesterolemia is common among tuberculous patients and is associated with mortality in miliary cases. Some in vitro studies have shown that cholesterol is necessary for the good functioning of macrophages and lymphocytes. STUDY OBJECTIVES: To determine whether a cholesterol-rich diet could accelerate sputum sterilization in patients with pulmonary tuberculosis. DESIGN: An 8-week follow-up, randomized, controlled trial carried out from March 2001 to January 2002. SETTING: A third-level hospital for respiratory diseases in Mexico City. PATIENTS AND INTERVENTIONS: Adult patients with newly diagnosed pulmonary tuberculosis were hospitalized for 8 weeks and randomly assigned to receive a cholesterol-rich diet (800 mg/d cholesterol [experimental group]) or a normal diet (250 mg/d cholesterol [control group]). All patients received the same four-drug antitubercular regimen (ie, isoniazid, rifampin, pyrazinamide, and ethambutol). MEASUREMENTS AND RESULTS: Every week, a quantitative sputum culture and laboratory tests were done and respiratory symptoms were recorded. Patients in the experimental group (10 patients) and the control group (11 subjects) were HIV-negative and harbored Mycobacterium tuberculosis that was fully sensitive to antitubercular drugs. Sterilization of the sputum culture was achieved faster in the experimental group, as demonstrated either by the percentage of negative culture findings in week 2 (80%; control group, 9%; p = 0.0019) or by the Gehan-Breslow test for Kaplan-Meier curves (p = 0.0037). Likewise, the bacillary population decreased faster (p = 0.0002) in the experimental group. Respiratory symptoms improved in both groups, but sputum production decreased faster in the experimental group (p < 0.05). Laboratory test results did not differ between the groups. CONCLUSIONS: A cholesterol-rich diet accelerated the sterilization rate of sputum cultures in pulmonary tuberculosis patients, suggesting that cholesterol should be used as a complementary measure in antitubercular treatment.

Adult↗

Effect of Gnaphalium conoideum HBK on guinea pig airway smooth muscle: role of L-type Ca2+ channels.

Plants from the Gnaphalium genus have been used in the Mexican traditional medicine for digestive and respiratory complaints. In the present study, the effect of methanolic extract from Gnaphalium conoideum HBK on the responses to contractile agonists was assessed in guinea pig tracheas, and the possible role of L-type Ca2+ channels was explored in tracheal guinea pig isolated myocytes. Cumulative concentration-response curves to carbachol or histamine, as well as contractile responses to 60 mM KCl were evaluated with or without 30 min preincubation with 20 or 100 microg ml(-1) Gnaphalium conoideum. Likewise, intracellular Ca2+ concentrations were measured by microfluorometric method (fura-2 AM) in isolated tracheal myocytes with or without preincubation with 0.1, 0.31 or 1 microg ml(-1)Gnaphalium conoideum. We found that methanolic extract from Gnaphalium conoideum significantly diminished the contractile responses to histamine, but not to carbachol or KCl. In isolated myocytes, Gnaphalium conoideum significantly reduced the intracellular Ca2+ rise induced by 60 mM KCl. Because histamine contractile responses are largely dependent on extracellular Ca2+, and KCl responses are mainly mediated through L-type Ca2+ channels, our results suggested that methanolic extract from Gnaphalium conoideum might be acting as a partial blocker of these Ca2+ channels.

Animals↗

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase.

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D(4) (LTD(4)) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD(4), but not leukotriene C(4) (LTC(4)), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC(4) nor LTD(4) modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca(2+) ([Ca(2+)](i)) and contraction, histamine or carbachol produced a transient Ca(2+) peak followed by a plateau, along with a contraction. LTD(4) increased the histamine-induced transient Ca(2+) peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD(4) were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD(4) significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca(2+) channel participation in the hyperresponsiveness to histamine was discarded because LTD(4) did not modify the [Ca(2+)](i) changes induced by KCl. In tracheal myocytes, LTD(4) enhanced the transient Ca(2+) peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca(2+) refilling. Genistein abolished this last LTD(4) effect. Partial blockade of the SR-ATPase Ca(2+) pump with cyclopiazonic acid reduced the Ca(2+) transient peak induced by histamine but not by carbachol. These results suggested that LTD(4) induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca(2+) pump activity. L-type Ca(2+) channels seemed not to be involved in this phenomenon.

Animals↗

Possible role of substance P in the ischemia-reperfusion injury in the isolated rabbit lung.

The origin of the endothelial damage leading to the ischemia-reperfusion injury after lung transplantation has not been elucidated. We postulated that neurotransmitters released during the preservation of the donor lung might explain this vascular derangement. Thus, in isolated rabbit lungs preserved over 24 hours, we evaluated the release of acetylcholine (ACh) and substance P (SP), the activity of their major degrading enzymes, acetylcholinesterase (AChE) and neutral endopeptidase (NEP), and changes in the capillary permeability. Both neurotransmitters showed the highest release rate in the first 15 minutes, followed by a sharp exponential decrement at 1, 6, 12 and 24 hours. AChE and NEP activities showed no variation at these time intervals. Basal capillary permeability significantly increased (P<0.01) after 24 hours preservation with saline. This increased permeability was avoided (P<0.01) by the SP fragment 4-11 (an SP receptors antagonist), but not by atropine. These results suggest for the first time a pathogenic role of SP in the ischemia-reperfusion injury, and thus the potential usefulness of SP antagonists as additives in the lung preservation solutions should be explored.

Animals↗

Spontaneous changes in guinea-pig respiratory pattern during barometric plethysmography: role of catecholamines and nitric oxide.

Barometric plethysmography for unrestrained animals is a non-invasive method that allows repetitive measurements of pulmonary function, but habituation of the conscious animal to this technique has not been explored. Respiratory frequency (f(R)) and 'enhanced pause' (P(enh)) were measured by barometric plethysmography for a period of 8 h in guinea-pigs. Compared with basal values, during the first hour of recording a progressive increase in P(enh) (up to 25-50%) and a corresponding decrease in f(R) were recorded, followed by a relative plateau in each for up to 8 h. These changes were avoided by a 30-min pretreatment with propranolol and l-NAME (nitric oxide synthase inhibitor), with P(enh) values as high as this plateau phase since the beginning of recording. Atropine, salbutamol or budesonide did not modify the progressive increment in P(enh). We concluded that catecholamines and nitric oxide are released when guinea-pigs are introduced into the plethysmographic chamber, leading to initial low P(enh) values. These mediators probably diminish owing to habituation of the animal to the new environment, with an apparent progressive increment in P(enh). These spontaneous changes in P(enh) and f(R) must be taken into account during barometric plethysmography in order to avoid misinterpretation of the results.

Animals↗

Effect of BCG vaccination in asthmatic schoolchildren.

Recent studies have explored the effect of Bacilli Calmette-Guerin (BCG) or Mycobacterium vaccae vaccination in asthmatic patients, yielding conflicting results. We investigated the effect of BCG vaccination in asthmatic schoolchildren, especially focusing on the cytokine pattern released by mononuclear cells. After a 1-yr run-in period, 67 asthmatic schoolchildren received intradermal immunization with BCG (33 patients) or placebo (34 patients). Both groups were followed during 1 yr. Serum immunoglobulin E (IgE) levels did not change after BCG (407.1 +/- 86.6 vs. 415.1 +/- 86.7 IU/ml, mean +/- s.e.m.), but increased after placebo (406.7 +/- 67.0 vs. 619.7 +/- 90.7 IU/ml, p = 0.001) administration. Interleukin (IL)-4 and interferon (IFN)-gamma measured in the supernatant of stimulated cultured blood mononuclear cells did not change in the BCG group (10.8 +/- 2.3 vs. 17.9 +/- 5.7 pg/ml, and 348.6 +/- 118.0 vs. 354.8 +/- 139.0 pg/ml, respectively), while in the control group IL-4 increased (from 6.7 +/- 1.3 to 16.1 +/- 6.0 pg/ml, p < 0.05), and IFN-gamma decreased (from 279.9 +/- 82.1 to 232.1 +/- 109.6 pg/ml, p = 0.01). In comparison with their initial status, most patients maintained the same asthma severity and the same proportion of emergency room visits at the end of the study. The proportion of those in whom asthma improved or worsened was the same in both groups. We concluded that, contrary to the common hypothesis, BCG vaccination in asthmatic children was unable to cause a long-term reinforcement of Th(1) response, although it could avoid the increased Th(2) response observed in control patients.

Asthma↗

Trends of asthma in Mexico: an 11-year analysis in a nationwide institution.

STUDY OBJECTIVES: Asthma prevalence is increasing in many countries. Some recent articles, however, claim that this tendency is ending. Our aim was to investigate asthma trends in Mexico. DESIGN: Annual data on health services provided to asthmatic patients were retrospectively analyzed from 1991 to 2001. SETTING: The Instituto Mexicano del Seguro Social, the largest nationwide medical institution in Mexico (approximately 24 to 32 million insured subjects). PARTICIPANTS: Health services provided to subjects of any age. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Asthma-associated health services, either expressed as absolute number or as rate per insured subjects, progressively increased until 1997 in family physician office visits (FPOVs) [newly diagnosed cases only], emergency department visits (ERVs), and hospital discharges (HDs). From that year onward, the number and rates of asthma-associated health services decreased. The same trends were observed for age groups 0 to 4 years, 5 to 14 years, 15 to 44 years, and 45 to 64 years. Using a different approach, asthma was diagnosed each year in approximately 0.4% of all FPOVs, but a decrease in this percentage was observed from 1997 onward. Likewise, asthma caused increasing percentages of all ERVs and HDs until 1997, followed by a sharp decline thereafter. CONCLUSIONS: A decline in absolute and relative numbers of asthma-associated health services occurred over recent years in all medical settings, suggesting that the epidemic of new asthma cases is ending and/or that better control of the disease has been achieved.

Adolescent↗

Sweat conductivity and chloride titration for cystic fibrosis diagnosis in 3834 subjects.

Sweat test is the standard for cystic fibrosis (CF) diagnosis. Conductivity is an alternative method not yet approved, in spite of its good correlation with chloride concentration. The aim was to assess the capacity of sweat conductivity to discriminate between CF and non-CF subjects. Automated measurements of conductivity and chloride concentration were carried out on the same sweat samples from subjects with clinical suspicion of CF. Sweat samples from 3,834 subjects, median age 1.8 years (range 1 month-54 years) were analysed, and those with chloride titration >60 mmol/l were considered as CF patients (n=294). Conductivity median values in CF and non-CF subjects were 111 mmol/l (82-148) and 36 mmol/l (12-89), respectively. The Spearman correlation between chloride titration and conductivity was r=0.60 (P<0.001). The receiver operating characteristics (ROC) curve showed very high agreement between two methods. The best conductivity cut-off value to diagnose CF was > or =90 mmol/l (sensitivity 99.7%, specificity 100%, positive and negative predictive values of 100% and 99.97%, respectively, and kappa=0.998). Likewise, the best conductivity cut-off value to exclude CF was <75 mmol/l. The sweat conductivity method showed good correlation with chloride titration, and accurately discriminated between subjects with and without CF. In accordance with this, CF diagnosis might be confirmed for conductivity values > or =90 mmol/l and excluded for <75 mmol/l. Values between 75 and 89 mmol/l should correspond to an equivocal range. However, more studies are needed to confirm the role of conductivity in definitive CF diagnosis.

Adolescent↗

Acetylcholine and tachykinins involvement in the caffeine-induced biphasic change in intracellular Ca2+ in bovine airway smooth muscle.

1. Caffeine has been widely used as a pharmacological tool to evaluate Ca(2+) release from the sarcoplasmic reticulum in isolated smooth muscle cells. However, in nervous tissue this drug also causes neurotransmitters release, which might cause additional effects when smooth muscle strips are evaluated. To assess this last possibility, simultaneous measurements of contraction and cytosolic Ca(2+) concentration (using Fura-2/AM) were carried out in bovine airway smooth muscle strips during caffeine stimulation. 2. A first stimulation (S1, n=11) with caffeine (10 mM) induced a biphasic change in cytosolic Ca(2+), which consisted of a transient Ca(2+) peak (254+/-40 nM, X+/-SEM) followed by a plateau (92+/-13 nM), and a transient contraction (204.72+/-31.56 mg tension mg tissue(-1)). A second caffeine stimulation (S2) produced a similar response but these parameters had a different magnitude. The S2/S1 ratios for these parameters were 0.69+/-0.02, 0.83+/-0.06 and 1.01+/-0.03, respectively. Addition of omega-conotoxin GVIA (1 micro M) and tetrodotoxin (3.1 micro M) before S2 significantly diminished these S2/S1 ratios (0.26+/-0.05, 0.26+/-0.09 and 0.64+/-0.11, respectively, n=5, P<0.05), implicating the neurotransmitters release involvement in the response to caffeine. A similar effect (P<0.01) was observed with atropine (1 micro M, n=4), the fragment 4-11 of substance P (SP) (an SP receptor antagonist, 10 micro M, n=5), and with both substances (n=4). 3. We discarded a direct effect of omega-conotoxin GVIA (1 micro M) plus tetrodotoxin (3.1 micro M) or of atropine (1 micro M) plus SP fragment 4-11 on smooth muscle cells because they did not modify caffeine responses in isolated tracheal myocytes. 4. We confirmed by HPLC that caffeine increased the release of acetylcholine (from 0.43+/-0.19 to 2.07+/-0.56 nM mg tissue(-1), P<0.02) in bovine airway smooth muscle strips. Detection of substance P by ELISA was not statistically different after caffeine stimulation (geometric means before and after caffeine, 0.69 vs. 1.97 pg ml(-1) mg tissue(-1), respectively, P=0.053). 5. We concluded that acetylcholine and tachykinins release are involved in the caffeine-induced biphasic changes in cytosolic Ca(2+) concentration.

Acetylcholine↗

Spirometric changes in fire-eating subjects in Mexico City.

BACKGROUND: Fire-eating is an activity mainly carried out by inner-city poorest subjects as a way to obtain money. Scant information has been reported concerning the consequences of this activity on lung function. METHODS: This study was accomplished in the streets of Mexico City by performing spirometric studies on 30 fire-eaters prior to and after their daily activity; in 16 of these subjects these studies were also conducted after salbutamol inhalation. RESULTS: All fire-eaters were males, 27.9 +/- 1.1 years of age (mean +/- standard error of the mean). Up to two thirds showed abnormalities in baseline spirometry (11 with an obstructive pattern and 9 with mixed pattern) not related to a smoking habit or drug abuse. Number of years in the fire-eating activity was inversely correlated with FEF50 (r=-0.46, p<0.01) and FEF75 (r=-0.33, p<0.05). Likewise, body mass index was inversely correlated with FEF25 and FEF50. These results were corroborated with multiple regression analysis. At the end of daily fire-eating activity, further diminution of FEF75 was observed (-7.6 +/- 1.4%, p<0.01). Aerosolized salbutamol caused statistically significant increment (p<0.05 to p<0.01) in nearly all spirometric variables, although on an individual basis only 10 of 16 (63%) had positive bronchodilation response. CONCLUSIONS: Fire-eaters showed a mild decrease of airflows, which partially correlated with number of years spent in this activity. After a 1-day fire-eating activity, further airflow limitation increased. Up to 63% of subjects tested improved some spirometric airflow value after salbutamol inhalation.

Adult↗

Effect of acute ozone exposure on pregnant rat uterus contractile responses.

Pulmonary effects of ozone (O(3)) inhalation have been comprehensively studied, but little is known about its extrapulmonary consequences, particularly in the reproductive tract. Thus, the effects of an acute O(3) exposure on the contractile response of the pregnant rat uterus were evaluated. Nonpregnant and pregnant (5, 10, and 18 days of gestation) rats were exposed to air or O(3) (3 ppm) for1 h, and uterine strips isolated from these animals were studied 16-18 h later. Contractile responses to acetylcholine (ACh) and oxytocin (OT) were evaluated with respect to three parameters (area under the curve, amplitude, and frequency). O(3) did not modify the sensitivity (-logEC(50)) to either agonist at any pregnancy stage, but induced a statistically significant increase in all maximum responses to OT at gestational day 5, and increased the maximum response (area under the curve) to ACh at pregnancy days 5 and 10. Our results suggest that O(3) inhalation can produce abnormal contractility in the pregnant uterus, and identify the need for further investigation of this issue.

Acetylcholine↗