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Biomedical subjects

M H Vargas

Publications and source records attributed to M H Vargas.

At least 19 recordsLinked to original sources

Effect of altitude on the frequency of pulmonary tuberculosis.

SETTING: Pulmonary tuberculosis (PTB) incidence greatly varies around the world, a phenomenon usually attributed to socio-economic factors or health service availability. A recent study, however, indicated that PTB was inversely related to altitude. OBJECTIVE: To evaluate factors associated with PTB notification rates in Mexico. METHODS: Annual notification rates (1998-2002) of PTB in each of the 32 Mexican states were analysed, and likely factors were assessed through correlation and multiple regression analyses. RESULTS: Most variables lacked association with PTB rates, including percentage of population aged > or = 65 years, population density, percentage of population with < or = 2 minimum salaries, percentage of population with social security, level of education, diabetes incidence, percentage of immigration, percentage of rural population and a global marginalisation index. Only altitude above sea level correlated with tuberculosis incidence (r = -0.74, P < 0.0001). Likewise, in the multiple regression analysis only altitude reached a statistically significant association. CONCLUSION: Our results showed that altitude had a strong inverse relationship to PTB notification rates in Mexico, which might be related to the well known changes in alveolar oxygen pressure at different altitudes. Interestingly, several factors traditionally considered as predisposing conditions for the development of PTB did not correlate with the disease.

Adolescent↗

[Bronchial nodules produced by Strongyloides stercoralis as the cause of bronchial obstruction].

Infection by Strongyloides stercoralis can cause asthma-like symptoms through mechanisms that have not yet been clarified. A 55-year-old male farm worker with a 2-year history of illness diagnosed as asthma and treated unsuccessfully with bronchodilators and corticosteroids was referred to our hospital with severe dyspnea. The initial chest radiograph showed mild air trapping, and pulmonary function tests detected airway obstruction that did not respond to salbutamol. Bronchoscopy revealed multiple nodules protruding into the airway lumen. S. stercoralis larvae were detected in bronchoalveolar lavage fluid and stool samples. Although treatment with albendazole was initiated, the patient's condition worsened over the next 3 days, hemoptysis presented, and the process ended in death. Autopsy demonstrated Strongyloides larvae in the bronchial nodules. Infection by S. stercoralis should be considered in the differential diagnosis of asthmatic-like symptoms refractory to treatment. In such cases nodules may be responsible for obstruction.

Animals↗

Diabetes modifies the male:female ratio in pulmonary tuberculosis.

SETTING: Socio-cultural factors have been invoked to explain the male predominance among patients with pulmonary tuberculosis, but there is no conclusive evidence of their role. OBJECTIVE: To assess male predominance in a group of diabetics with pulmonary tuberculosis compared with patients with pulmonary tuberculosis alone. DESIGN: Clinical records of in-patients with pulmonary tuberculosis and with (TBDM group, n = 202) or without (TB group, n = 226) diabetes mellitus were reviewed, and the male percentages in each of six age groups (15-29, 30-39, 40-49, 50-59, 60-69, > or = 70 years) calculated. RESULTS: In the TB group, no gender difference (51% males) was found in the first age period, followed by a male predominance thereafter (71%, 68%, 75%, 63% and 58%). The TBDM group showed a similar pattern in the first two age groups (56% and 74%), followed by a steadily decline (r(S) = -0.90, P = 0.04) in male percentage (60%, 44%, 45%, 27%), leading to a female predominance after age 50. The association of age and gender was also corroborated by logistic regression in TBDM (P = 0.02), but not in TB (P = 0.19) patients. CONCLUSIONS: Diabetes was associated with a progressive shift of male predominance in pulmonary tuberculosis. Because diabetes is a disease that affects social activities similarly in men and women, our results suggest that factors other than socio-cultural ones are also important for determining the male predominance in pulmonary tuberculosis.

Adolescent↗

Main diagnosis and cause of death in a neonatal intensive care unit: do clinicians and pathologists agree?

AIM: To determine the agreement rates between clinical and autopsy diagnoses in a neonatal intensive care unit (NICU), distinguishing between the main diagnosis and cause of death. METHODS: Clinical and autopsy records of 75 infants who died in two consecutive years in the NICU (autopsy rate 42.6%) of a pediatric hospital in Mexico City were reviewed. RESULTS: Ninety-two percent of main clinical diagnoses were confirmed by autopsy. Four conditions (congenital cardiopathy, prematurity, specific congenital syndromes and hyaline membrane disease) accounted for more than two-thirds of diagnoses. However, for cause of death, the global agreement was only 50%. The most common conditions considered by clinicians (77%) and pathologists (56%) to be the causes of death were cardiogenic, septic or mixed shocks. Additionally, clinicians omitted 34 relevant conditions in 30 (40.0%) patients, and 21 of these conditions possibly played a role in the deaths of 17 (22.7%) patients. The most frequently omitted diagnosis was pneumonia, in 9 (26.5%) patients. Omissions were not related to gestational age, age at death, days as an inpatient, or gender. CONCLUSION: Despite a high agreement rate in the main diagnoses, notable imprecisions were present regarding cause of death and antemortem overlooking of potentially fatal conditions, confirming the useful role of autopsy to verify clinical diagnoses and suggesting that differentiation between the main diagnosis and cause of death should be carried out in future studies.

Autopsy↗

Results of a 12-month regimen for drug-resistant pulmonary tuberculosis.

SETTING: Several therapeutic regimens for drug-resistant tuberculosis have been suggested, most of them with a total duration of 18-24 months. OBJECTIVE: To report our experience using a shorter regimen. DESIGN: Fifty patients with drug-resistant pulmonary tuberculosis were managed by withdrawing all anti-tuberculosis drugs until the results of a drug sensitivity test were obtained (approximately 3 months), and then a 12-month self-administered regimen with four to six anti-tuberculosis drugs at full daily doses was initiated, based primarily on the sensitivity test and secondarily on the history of previous treatment. RESULTS: In 31 patients treatment was completed as planned, in six it was irregular and 13 definitively abandoned it. In the best scenario, 90.3% (28/31) of patients with full treatment were cured; this outcome was similar for both multidrug-resistant (MDR, n = 18, 88.9%) and non-MDR (n = 13, 92.3%) patients. Six months later, the relapse rate was 4.8%, and after a 5-year follow-up 14 out of 18 cured patients who were located remained asymptomatic (77.8%). If the worst scenario was applied, a 62.0% cure rate (31/50) was obtained. CONCLUSIONS: A 12-month regimen with a minimum of four anti-tuberculosis agents at full dose, essentially selected on drug sensitivity testing, could be an alternative option for the treatment of drug-resistant pulmonary tuberculosis.

Adolescent↗

Galphimia glauca organic fraction antagonizes LTD(4)-induced contraction in guinea pig airways.

Galphimia glauca is used for the treatment of asthma and allergies in Latin American traditional medicine. The ethylacetate fraction from its aerial parts was assayed for bronchoconstriction induced by antigen and several agonists in guinea pig tracheae. The organic fraction significantly inhibited the contractile response to ovalbumin in tracheae from sensitized guinea pigs, and significantly and selectively inhibited the bronchoconstriction induced by leukotriene D(4) (LTD(4)). The relative potency of the ethylacetate fraction of G. glauca to produce a concentration-dependent rightward shift of LTD(4) concentration-response curve was similar to that reported for SK&F 104353, a well-known competitive LTD(4)-antagonist.

Animals↗

Differences between inhaled and intravenous bronchial challenge to detect O(3)-induced hyperresponsiveness.

Ozone (O(3))-induced airway hyperresponsiveness in laboratory animals is usually demonstrated through dose-response curves with inhaled or intravenous bronchoconstrictor agonists. However, comparability of these two routes has not been well documented. Thus guinea pig airway responsiveness to ACh and histamine was evaluated 16-18 h after O(3) (3 parts/million, 1 h) or air exposure by two plethysmographic methods (spontaneously breathing and mechanically ventilated) and by two administration routes (inhalatory or intravenous). We found that O(3) caused airway hyperresponsiveness to intravenous, but not to inhaled, agonists, independent of the plethysmographic method used. Suitability of the inhalatory route to detect airway hyperresponsiveness was corroborated with inhaled ACh after an antigen challenge or extending O(3) exposure to 3 h. Acetylcholinesterase activity was not modified after O(3) exposure in lung homogenates and blood samples. Thus inhaled agonists were less effective to reveal the airway hyperresponsiveness after an acute O(3) exposure than intravenous ones, at least for the 1-h exposure to 3 parts/million, and this difference seems not to be related to an O(3)-induced inhibition of the acetylcholinesterase activity.

Acetylcholinesterase↗

Atypical radiological images of pulmonary tuberculosis in 192 diabetic patients: a comparative study.

SETTING: Comparative studies of pulmonary tuberculosis images in diabetics have yielded conflicting results. OBJECTIVE: To assess radiological images of pulmonary tuberculosis in a large population of diabetic patients. DESIGN: Radiographs from in-patients admitted with pulmonary tuberculosis and diabetes (TBDM group, n = 192) were reviewed and compared with a control group of patients with pulmonary tuberculosis alone (TB group, n = 130). RESULTS: Both groups had a similar evolution time of tuberculosis (approximately 2 years). Statistical differences were observed as follows: TBDM patients were older (51.3+/-0.9 vs. TB group 44.9+/-1.8 years, mean +/- SEM), and had a decreased frequency of upper (17% vs. 56%), and an increased frequency of lower (19% vs. 7%) and upper + lower (64% vs. 36%) lung field lesions. More TBDM patients developed cavitations (82% vs. 59%) more often in the lower lung fields (29% vs. 3%). More multiple cavities were seen in TBDM patients (25% vs. 2%). TBDM group had a lower total leukocyte count (8836.7+/-219.5 vs. 10013.1+/-345.2 cells/mm3), mainly due to a lower number of non-lymphocyte cells (6815.8+/-221.8 vs. 8095.7+/-321.9 cells/mm3). Multiple logistic regression showed that being a diabetic patient was the most important factor determining lower lung field lesions and cavities. CONCLUSIONS: This study in a large number of diabetics with pulmonary tuberculosis confirmed that their chest X-ray images significantly depart from the typical presentation. Clinicians must keep this in mind to avoid misdiagnosis.

Adult↗

Progressive age-related changes in pulmonary tuberculosis images and the effect of diabetes.

Atypical radiologic images of pulmonary tuberculosis are common in elderly and in diabetic patients. To investigate the relationship of chest radiographic findings of tuberculosis to age in diabetic and nondiabetic patients, we compared the chest radiographic findings of 192 inpatients with pulmonary tuberculosis and diabetes with those of 130 patients with pulmonary tuberculosis alone. The proportion of patients with lower lung field lesions progressively increased with age (r(S) = 0.89, p < 0.01), whereas the frequency of cavitation steadily decreased with age (r(S) = -0.79, p < 0.05). In diabetic patients, a high frequency of lower lung lesions and cavitation was observed in all age groups. We speculated that, in older patients and in diabetics, the increased alveolar oxygen pressure in the lower lobes favors development of lower lobe disease in these groups.

Adolescent↗

Identification of mechanisms involved in the acute airway toxicity induced by parathion.

Organophosphates are still widely used worldwide and cause thousands of intoxications every year. In this work we investigated the mechanisms of parathion (Pth) airway toxicity, using biochemical and functional approaches. A plethysmographic technique for unrestrained guinea pigs was used to analyze Pth-induced modifications of airway mechanics and responsiveness to acetylcholine (ACh: 0.1-3.2 mg/ml, 2-min inhalation each dose). The isolated perfused rabbit lung preparation was used to study the acute effects of Pth on airway responsiveness to ACh (10(-8)-10(-3) M), histamine (10(-8)-10(-3) M) and substance P (10(-10)-10(-6) M), pulmonary acetylcholinesterase inhibition and cytochrome P450 (P450) activity, and their modifications with previous administration of Pth (1 mg/kg s.c. daily, 7 days). We found that: (1) In guinea pigs Pth (3.2-17 mg/kg i.p.) produced a dose-dependent increase in a lung resistance index (iRL), which was greatly reverted (approximately 50%) by salbutamol (2 mg/ml, 2-min inhalation, or 10 microg/kg i.p.). This salbutamol effect was transient (5-10 min), suggesting that this bronchodilator triggered additional obstructive mechanisms. (2) Pth increased the water content in lung parenchyma samples, but not in trachea or bronchi, and augmented the respiratory secretions measured through monosaccharide content in bronchoalveolar lavage. (3) The increase in iRL was greater in female animals, probably due to a higher P450 basal activity, and completely blocked by pharmacological inhibition of P450 with piperonyl butoxide (500 mg/kg i.p.). (4) In male guinea pigs a subclinical dose of Pth (10 mg/kg i.p.) induced airway hyperresponsiveness to ACh. In isolated perfused rabbit lung Pth (10(-6) M) produced airway hyperresponsiveness to ACh and histamine, the latter prevented by atropine (10(-5) M). (5) Repetitive exposure to subclinical doses (1 mg/kg s.c.) of Pth during 1 week caused approximately 80% inhibition of P450 activity in rabbits, which was not enough, however, to prevent the functional manifestation of Pth toxicity in the airways.

Acetylcholinesterase↗

Interactions between cytochrome P-450 activities and ozone-induced modulatory effects on endothelial permeability in rabbit lungs: influence of gender.

The effects of rabbit exposure to ozone (O(3)) (0.4 ppm for 4 h) on two different cytochrome P-450 (CYP450)-dependent activities were investigated. In turn, the role of CYP450 in the inhibitory effect of O(3) on acetylcholine (ACh)-evoked increase in endothelial permeability was also assessed. Immediately after the period of exposure, rabbits of both sexes were sacrificed and their lungs were extracted. Some lungs were used for preparation of microsomes and measurement of 7-ethoxyresorufin O-deethylase (EROD) and parathion oxidase activities. Other rabbit lungs were isolated and recirculatingly blood-free perfused. Arterial, venous pressures, and lung weight were continuously recorded. Capillary pressure was measured by applying the double occlusion method. Capillary filtration coefficient (K(f,c)) was evaluated by measuring the amount of fluid filtering through the endothelium when vascular pressures were suddenly increased. Dose-response curves to ACh were constructed in air- or O(3)-exposed rabbits. Some animals were pretreated with piperonyl butoxide (PBO), a well-known inhibitor of CYP450. O(3) significantly reduced both EROD and parathion oxidase lung microsomal activities in females, while it had no effect in males. Exposure to O(3) strongly inhibited the ACh-induced increase in K(f,c). Pretreatment with PBO reversed the modulatory effect of O(3) on endothelial permeability in male rabbits, but not in females. It was concluded (1) that inhibition of 2 different CYP450-dependent activities after exposure to 0.4 ppm O(3) for 4 h appears to be a gender-dependent phenomenon, and (2) that CYP450 is probably involved in the O(3)-evoked inhibitory mechanism against ACh-induced increase in endothelial permeability, but only in males.

Animals↗

Does aging modify pulmonary tuberculosis?: A meta-analytical review.

STUDY OBJECTIVES: To evaluate the differences in the clinical, radiologic, and laboratory features of pulmonary tuberculosis (TB) in older patients, as compared to younger patients. DESIGN: A meta-analysis (the Schmidt-Hunter method) of published works found in MEDLINE and other sources was performed. A total of 12 studies were collected, and each variable was submitted to meta-analysis. RESULTS: No differences were found between older (>/= 60 years old) and younger TB patients with respect to male predominance, evolution time before diagnosis, prevalence of cough, sputum production, weight loss, fatigue/malaise, radiographic upper lobes lesions, positive acid-fast bacilli in sputum, anemia or hemoglobin level, and serum aminotransferases. A lower prevalence of fever, sweating, hemoptysis, cavitary disease, and positive purified protein derivative, as well as lower levels of serum albumin and blood leukocytes were noticed among older patients. In addition, the older population had a greater prevalence of dyspnea and some concomitant conditions, such as cardiovascular disorders, COPD, diabetes, gastrectomy history, and malignancies. CONCLUSIONS: This meta-analytical review identified the main differences of older TB patients, as compared to younger TB patients, that should be considered during the diagnostic evaluation. Most of these differences are explained by the already known physiologic changes that occur during aging.

Adolescent↗

Asthma and geographical altitude: an inverse relationship in Mexico.

Motivated by the great asthma-prevalence variation throughout the world, we analyzed the rate variation of medical services due to asthma in the 32 Mexican states at the Instituto Mexicano del Seguro Social (approximately 24 million insured subjects). In 1993, a total of 406,036 services were due to asthma, and state rates ranged from 53 to 476 x 10,000 insured subjects. A direct correlation (p < 0.05) was found for single-room house, ascariasis, and rubella rates, but the strongest (inverse) correlation was found for geographical altitude (r = -0.73, p < 10(-5)). Thus, in Mexico, geographical altitude affects the etiological factor(s) responsible for the development of asthma or for the triggering of asthma attacks.

Altitude↗

Comparison of ozone-induced effects on lung mechanics and hemodynamics in the rabbit.

The effects of rabbit exposure to ozone (O3)(0.4 ppm for 4 h) on pulmonary mechanical properties and hemodynamics have been investigated on the isolated perfused lung model. Tracheal pressure, airflow, and tidal volume were measured in order to calculate lung resistance (RL) and dynamic compliance (Cdyn). Using the arterial/venous/double occlusion method, the total pressure gradient (deltaPT) was partitioned into four components (arterial, pre-, postcapillary and venous). Dose-response curves to acetylcholine (ACh), substance P (SP), and histamine were constructed in lungs isolated from rabbits immediately or 48 h after air or O3 exposure O3 induced a significant increase in the baseline value of deltaPt, more markedly 48 h after the exposure. Immediately after the exposure, O3 partly inhibited the ACh-, SP-, and histamine-induced decreases in Cdyn and increases in RL. This inhibitory effect was still in part present 48 h after O3 treatment. In the groups studied immediately after exposure, O3 did not significantly modify the ACh-, SP-, and histamine-induced vasoconstriction. Forty-eight hours after exposure, O3 induced a contractile response to ACh and SP in the arterial segment but decreased the response to histamine. We conclude that O3 can induce direct vascular constriction. Directly, but also 48 h after exposure, O3 can inhibit the ACh-, SP-, and histamine-induced changes in lung mechanical properties. Ozone can also induce some changes in the intensity and in the location of the vascular responses to ACh, SP, and histamine.

Acetylcholine↗

Guinea pig lung resistance shows circadian rhythmicity not influenced by ozone.

Increased circadian variability of airway caliber is a key feature of asthmatic patients, but it has not been addressed in animal models of asthma. Furthermore, animal studies on circadian rhythmicity of airway resistance are very scanty. We used a plethysmographic method for unrestrained guinea pigs to monitor a lung resistance index (iRL) during 24 h. We found circadian variability of iRL values, which were fitted by a sinusoidal curve. Acrophase and bathyphase, characterizing the timing of narrowest and widest airway caliber, respectively, were found at 02:03, and 15:34 h. iRL values at these time-points were statistically different (P < 10(-5)). Moreover, average resistance during the dark period was significantly higher (P < 0.0001) than during the light period. Immediately after an acute ozone exposure (3 ppm for 1 h) an increase in iRL was demonstrated (P < 0.01), which lasted for 2 h, and tended to remain high for the next hour. After guinea pigs recovered from this obstruction, the circadian rhythm and variability of airway caliber were unaffected. Our results show that a circadian rhythm of iRL takes place in guinea pigs, greatly resembling what occurs in humans, and that ozone exposure causes a transient airway obstruction, but fails to reproduce the increased variability of airway caliber observed in asthmatic patients.

Airway Resistance↗

Airway involvement in hypersensitivity pneumonitis.

Exposure to organic particles causes, in a susceptible host, diffuse inflammation of the lung acinus. However, immunopathologic response may not be confined to the alveoli and may also involve the large and peripheral airways. Therefore, after allergen inhalation a clinical spectrum of respiratory disorders may be observed, including hypersensitivity pneumonitis, asthma, chronic airway obstruction, and simple chronic bronchitis. Hypersensitivity pneumonitis is not a uniform disease but a complex syndrome, and the involvement of the airways may occur alone, simultaneously with, or after the parenchymal disease.

Alveolitis, Extrinsic Allergic↗

Chronic exposure to ozone causes tolerance to airway hyperresponsiveness in guinea pigs: lack of SOD role.

Tolerance to respiratory effects of O3 has been demonstrated for anatomic and functional changes, but information about tolerance to O3-induced airway hyperresponsiveness (AHR) is scarce. In guinea pigs exposed to air or O3 (0.3 parts/million, 4 h/day, for 1, 3, 6, 12, 24, or 48 days, studied 16-18 h later), pulmonary insufflation pressure changes induced by intravenous substance P (SP, 0.032-3.2 micro ug/kg) were measured, then the animals were subjected to bronchoalveolar lavage (BAL). Bronchial rings with or without phosphoramidon were also evaluated 3 h after air or a single O3 exposure. O3 caused in vivo AHR (increased sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compared with control. However, after 48 days of exposure, O3 no longer caused AHR. Total cell, macrophage, neutrophil, and eosinophil counts in BAL were increased in most O3-exposed groups. When data from all animals were pooled, we found a highly significant correlation between degree of airway responsiveness and total cells (r = 0.55), macrophages (r = 0.54), neutrophils (r = 0.47), and eosinophils (r = 0.53), suggesting that airway inflammation is involved in development of AHR to SP. Superoxide dismutase (SOD) levels in BAL fluids were increased (P < 0.05) after 1, 3, 6, and 12 days of O3 exposure and returned to basal levels after 24 and 48 days of exposure. O3 failed to induce hyperresponsiveness to SP in bronchial rings, and phosphoramidon increased responses to SP in air- and O3-exposed groups, suggesting that neutral endopeptidase inactivation was not involved in O3-induced AHR to SP in vivo. We conclude that chronic exposure to 0. 3 ppm O3, a concentration found in highly polluted cities, resulted in tolerance to AHR to SP in guinea pigs by an SOD-independent mechanism.

Analysis of Variance↗