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Biomedical subjects

E Vargas

Publications and source records attributed to E Vargas.

At least 55 records · Page 3Linked to original sources

Oxidative polymorphism of debrisoquine is not related to human colo-rectal cancer.

The oxidative polymorphism of debrisoquine (DBQ) has been determined in 89 patients with colo-rectal cancer and in 556 normal control subjects. Four patients and 34 controls, with a metabolic ratio greater than 12.6, were classified as poor metabolisers of DBQ (n.s.). No difference was found in the distribution of the frequencies of the MR of DBQ between patients and controls. It is concluded that polymorphic oxidation of DBQ is not related to the risk of developing colo-rectal cancer in human beings.

Adult↗

Polymorphic oxidation of debrisoquine in lung cancer patients.

Oxidative polymorphism of debrisoquine (DBQ) was assessed in 84 patients (81 male) with histologically proven bronchogenic carcinoma and in 143 healthy male smokers. 80 (95%) patients and 133 (93%) controls, with a metabolic ratio (MR) below 12.6, were classified as extensive metabolisers of DBQ (no significant difference between patients and controls). Only 1 of the 73 patients with epidermoid or microcytic carcinomas was classified as a poor metaboliser (PM) (P = 0.031 compared with controls). 63 patients (75%) and 110 controls (77%) showed a very fast oxidative rate, with MR values under 1 (not significant). The EM phenotype of DBQ might be a secondary genetic risk factor for developing bronchogenic carcinoma in male smokers.

Aged↗

Polymorphic oxidation of debrisoquine in women with breast cancer.

Oxidative polymorphism of debrisoquine (DBQ) was determined in 98 women with breast cancer (mean age 59.2 years, SD 10.7; 18 were premenopausal when diagnosed), and in 446 healthy control women (mean age 25.4 years, SD 9.15). All of them were free of drug interactions with oxidation of DBQ. Ten patients (10.2%), all of them postmenopausal when diagnosed, and 423 controls (5.2%), with values for metabolic ratio of DBQ greater than 12.6, were classified as poor metabolizers (PM) of DBQ (p = 0.006). Relative risk for developing breast cancer among women with PM phenotype was 2.09 (95% confidence limits 0.97-4.48). The PM status of DBQ might be a secondary risk factor for breast cancer in postmenopausal women.

Adult↗

Does arterial PCO2 interfere with hypoxia in muscular metabolism in man?

To answer the question whether PCO2 affects the muscular metabolism, PO2, PCO2, pH, lactic acid concentration and hemoglobin were measured in the efferent muscular venous blood from common flexor digitorum, during forearm rhythmic exercise corresponding to VO2max. Exercise was carried out either in hypocapnic hypoxia i.e. in permanent high altitude residents and translocated lowlanders, or in hypercapnic hypoxia i.e. in chronic obstructive lung disease (COLD) patients. The results show that, during exercise: i) PO2 in muscular venous blood remains around 20 Torr in normoxia and hypocapnic hypoxia and even higher (25 torr) in COLD patients, despite low arterial PaO2, and ii) arterial and/or local PCO2 play a role in the control of the muscular blood flow. But we cannot conclude that a change in PaCO2 affects muscular metabolism itself, because lactic acid in the muscular venous blood, that we used to check this effect, is likely dependent on mechanisms other than anaerobic glycolysis, such as a change in lactic acid efflux from the myocytes. The increase in muscular venous PCO2 may enhance the myocyte permeability to lactic acid during exercise.

Acclimatization↗

Haemodynamic and neurohumoral responses in elderly patients with postural hypotension.

Haemodynamic and neurohumoral responses to head-up tilt were measured in 28 elderly patients with postural hypotension (EPPH) and 12 healthy elderly subjects (HE). There were no differences in catecholamines between the groups and only noradrenaline increased on tilt (P less than 0.001). Plasma renin activity and aldosterone were similar in HE and EPPH in the supine and tilt positions. In both groups vasopressin increases (P = 0.032), and plasma volume decreases were the same (P = 0.673). Supine EPPH had higher heart rates (P = 0.019) but similar cardiac indices (P = 0.621). Both had similar changes on tilting (P = 0.975 and P = 0.341). Stroke volume decrease was higher in HE (35%) than EPPH (23%; P less than 0.001). HE showed an increase in peripheral resistance on tilting with no change in EPPH (P = 0.005). EPPH had larger coefficients of variation for all variables. The differences in haemodynamic responses and the similarity of neurohumoral responses during tilting suggest end-organ failure in EPPH with individual variations. Postural hypotension in old age is not a single entity.

Aged↗

Compliance of the respiratory system in infants born at high altitude.

Populations living at high altitude are known to have a number of distinctive physiologic traits, including an increase in lung volume and compliance. We asked whether the factors that result in the increased compliance of high altitude natives were sufficiently expressed in utero that an increase in respiratory system compliance (Crs) could be detected at birth. Measurements were performed at about 1 day after birth on 34 infants born in La Paz, Bolivia (3,600 m, Pb about 495 mm Hg) and 36 born in Santa Cruz (400 m, Pb about 735 mm Hg). All infants were full-term and healthy, with body weights of at least 2,700 g. We measured Crs from expirations within the tidal volume range by the multiple occlusion method. Breathing pattern was measured from the spirometric record, and an index of chest wall distortion was obtained from the ratio of volume and abdominal displacement during spontaneous breathing and relaxations against closed airways. Rib cage and abdomen dimensions did not differ between the two groups. Crs values in Santa Cruz were similar to those previously obtained in Montreal and in other Caucasian infant populations at low altitudes. Crs was 33% and Crs/kg 37% greater (p less than 0.001) in the high altitude group, which included equal numbers of Amerindians and Mestizos of European ancestry. Dynamic elevation of the end-expiratory level was similar in both groups. Ventilation/kg and the distortion ratio were slightly yet significantly higher in the high altitude infants, suggesting an increased ventilatory drive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Polymorphic oxidation of debrisoquine in bladder cancer.

The oxidative polymorphism of debrisoquine has been determined in 125 patients with bladder cancer and in 556 healthy control subjects; 96.6% of patients and 93.9% of controls with a metabolic ratio of debrisoquine less than 12.6 were classified as extensive metabolizers of debrisoquine (P = NS). The distribution of frequencies of metabolic ratio values tended to have lower values in the patients (P less than 0.05), reflecting a higher oxidative rate of debrisoquine in urothelioma patients that cannot be explained solely in terms of enzymatic induction by drugs, tobacco or alcohol. Patients with a high occupational risk for urothelioma had lower metabolic ratio values (P = 0.03). Our results suggest that oxidative polymorphism of debrisoquine might be related to the pathogenesis of bladder cancer.

Aged↗

Distribution of common carotid blood flow, measured by Doppler, in man at high altitude.

The aim of the work was to estimate the possible changes induced by high altitude in the distribution of the common carotid arterial blood flow towards the internal and external carotid arteries. Common carotid blood flow and internal and external blood velocities were measured in 20 lowlanders at sea level, in 5 of them over a 3-week period at 3800 m and in 20 permanent residents of this high altitude. Internal and external blood velocities were recorded with a continuous Doppler and blood flow was recorded by range-gated Doppler velocimeter. Common carotid blood flow was 15% higher in all subjects exposed to high altitude due to a lowering in downstream vascular resistance since systemic blood pressure did not change at high altitude. The increase of blood flow in the common carotid was the result of a rise mainly in the external carotid blood flow.

Acclimatization↗

Hypothermia in the elderly: sociomedical characteristics and outcome of 86 patients.

A comprehensive retrospective study analysing the case records of 86 hypothermic elderly patients who were treated according to a standard protocol in our department between 1980 and 1985 is presented. Hypothermia was found to occur not only in the frail, demented and disabled elderly men and women, but also in apparently healthy elderly individuals living with their families and in rest homes (40%). The level of consciousness was not related to the degree of hypothermia but to the underlying pathology. There was no correlation between the severity of hypothermia and mortality. Fatality was less among the group receiving substantial services, but the overall mortality within 48 hours was 36%. Early detection improved survival. Eleven per cent had recurrence of hypothermia and 90% of those who survived hypothermia died within one year. Prolonged duration of hypothermia, high levels of neutrophilia, blood urea and amylase, cardiac arrhythmias and impairment of consciousness were found to be associated with high mortality.

Aged↗

[Human life at high altitudes: myths and realities].

Life at high altitude presents very interesting biological and medical aspects. For countries such as the Andeans, it also has socio-economical implications. The most important towns of Bolivia are situated between 3,000 and 4,850 m. It's to say that a great percentage of the population is permanently staying there. Moreover owing to the improvement of the roads and transport, an extensive migration (professional life, business, tourism, sport) developed some years ago. At 3,000 to 4,850 m, an oxygen arterial pressure (PaO2) between 40 and 70 mm Hg is resulting from the environmental hypoxia. The adaptation to hypoxia takes place in two phases: --that incomplete, observed at short time in people who recently arrived, --that at very long time, observed in the native. The rapid arrival at more than 3,000 m, exposes the traveller to an hypoxic ventilatory stimulus which produces a hyperventilation response to increased PaO2. This hyperventilation brings out a decreasing of carbon dioxide arterial pressure (PaCO2) and alkalosis of the blood. This respiratory alkalosis seems to be responsible for most troubles which are present in the Acute Mountain Sickness linked to the CO2 role in cerebral blood circulation. At the same time but more slowly the classical high altitude polycythemia develops which permits compensate partially the hypoxic effect in 3 to 4 weeks. In the native the adaptation implies physiological variations of some parameters concerning the individual development. The principal studies showed that the native present a notable hyposensitivity to hypoxia and also to the stimulus CO2-H+. The Chronic Mountain Sickness patients have a less sensitivity to the same stimuli than the natives.

Adaptation, Physiological↗

Clinical prognostic indices of fatality in elderly patients admitted to hospital with acute pneumonia.

Acute pneumonia in the elderly is a common and serious condition. The importance of key clinical features and physical signs presenting to the junior hospital doctor was prospectively assessed in 100 consecutive patients admitted acutely to two hospitals. The most significant finding is that elderly patients with pneumonia who are found to be acutely confused at the time of presentation or who gave a previous history of chronic brain failure are much more likely to die than others. Thus such patients should be assessed with particular attention to the early diagnosis and vigorous treatment of pneumonia.

Acute Disease↗

Iron deficiency anemia and steady-state work performance at high altitude.

Thirty-seven young adult male highland residents at 3,600-4,100 m in La Paz, Bolivia, performed short-duration cycle ergometry at 60, 80, and 100% of maximal voluntary O2 consumption (VO2max). Three groups of subjects representing the high-altitude population mean hemoglobin (Hb), the 10th percentile Hb, and below the 1st percentile were examined to test the hypothesis that the relationship of exercise performance to Hb concentration is similar to those relationships established at low altitude. Anemic individuals (n = 8) had 23% lower voluntary VO2max and 28% lower maximal work loads compared with controls (n = 17) or marginally anemic subjects (n = 12) although the relationship of VO2 to work load was similar. Anemic individuals maintained significantly higher arterial O2 partial pressures and Hb saturations during heavy exercise (90 +/- 0.5 vs. 85 +/- 0.6%) in conjunction with a greater heart rate up to maximal effort. A significantly decreased erythrocyte 2,3-diphosphoglycerate (2,3-DPG)-to-Hb molar ratio (0.70 +/- 0.04 vs. 1.12 +/- 0.06), suggestive of a left-shifted dissociation curve in anemics, is in contrast to the expected right-shifted curve. Moderate anemics were similar to controls. Anemic individuals did not differ in arterial lactate concentration from controls at absolute work loads; anemics had significantly lower arterial lactate concentrations at maximal effort than controls with no differences in the work load-to-lactate relationship. In conclusion, O2 transport during exercise at high altitude seems unaffected by the Hb concentrations as low as the 10th percentile of the population mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulmonary gas exchange in Andean natives with excessive polycythemia--effect of hemodilution.

Pulmonary gas exchange in Andean natives (n = 8) with excessive high-altitude (3,600-4,200 m) polycythemia (hematocrit 65.1 +/- 6.6%) and hypoxemia (arterial PO2 45.6 +/- 5.6 Torr) in the absence of pulmonary or cardiovascular disease was investigated both before and after isovolemic hemodilution by use of the inert gas elimination technique. The investigations were carried out in La Paz, Bolivia (3,650 m, 500 mmHg barometric pressure). Before hemodilution, a low ventilation-perfusion (VA/Q) mode (VA/Q less than 0.1) without true shunt accounted for 11.6 +/- 5.5% of the total blood flow and was mainly responsible for the hypoxemia. The hypoventilation with a low mixed venous PO2 value may have contributed to the observed hypoxemia in the absence of an impairment in alveolar capillary diffusion. After hemodilution, cardiac output and ventilation increased from 5.5 +/- 1.2 to 6.9 +/- 1.2 l/min and from 8.5 +/- 1.4 to 9.6 +/- 1.3 l/min, respectively, although arterial and venous PO2 remained constant. VA/Q mismatching fell slightly but significantly. The hypoxemia observed in subjects suffering from high-altitude excessive polycythemia was attributed to an increased in blood flow perfusing poorly ventilated areas, but without true intra- or extrapulmonary shunt. Hypoventilation as well as a low mixed venous PO2 value may also have contributed to the observed hypoxemia.

Adult↗

Hypothermia in the elderly: management in a purpose-built chamber.

Results of treatment of 86 hypothermic elderly patients in a purpose-built chamber are presented. They were barrier-nursed, continuously monitored and treated by slow active rewarming by warm air. The early 24-hour mortality did not significantly differ from other published reports. The complications of 'rewarming shock' and 'after drop' were prevented. It is concluded that a specially built hypothermia room facilitates management of hypothermic elderly patients and is recommended in all geriatric departments.

Aged↗

Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure.

The pharmacokinetics of lisinopril were determined in 6 healthy young, 6 healthy elderly and 6 elderly patients with cardiac failure. Lisinopril (5 mg day-1) was administered for 7 days. Plasma lisinopril concentration was measured at 1, 2, 4, 6, 8 and 24 h on days 1 and 7 of the study. The two elderly groups had higher serum lisinopril concentrations than the healthy young subjects (P less than 0.05). There were no significant differences in any of the areas under the curve (AUC) for lisinopril plasma concentration (over time) between the healthy young and healthy elderly groups. The healthy young patients had AUC values on day 7 lower than elderly patients with cardiac failure (P less than 0.01). Creatinine clearance was correlated with lisinopril clearance (r = 0.63; P = 0.006) and with AUC on day 7 (r = -0.67; P = 0.004). Lisinopril clearance was different in the three groups (P less than 0.05): healthy young patients had the highest and elderly patients with cardiac failure the lowest values. Thus, in the elderly a reduced renal clearance of lisinopril leads to higher and more sustained blood levels. In elderly patients with cardiac failure, renal function should be estimated before lisinopril is prescribed as a reduction in dose may be appropriate.

Adult↗

Cardiovascular haemodynamics and the response of vasopressin, aldosterone, plasma renin activity and plasma catecholamines to head-up tilt in young and old healthy subjects.

Increasing age impairs the regulation of blood pressure during posture change. The neuro-humoral and cardiovascular responses to head-up tilt were analysed in carefully-screened young and healthy elderly individuals. Mean blood pressure was significantly higher in the elderly but there were no differences in total peripheral resistance, heart rate, stroke volume and cardiac index. Age-related interactions were observed in the control of mean blood pressure, heart rate and stroke volume. Total peripheral resistance increased and cardiac index decreased but there was no difference in their control in the young and old. Noradrenaline, vasopressin, plasma renin activity and aldosterone all increased in response to the tilt. These observations indicate differences in the neuroendocrine responses and cardiovascular haemodynamics of young and old healthy individuals to head-up tilt and are particularly important because of all observations were made simultaneously in the same subject. It is suggested that a similar approach should be adopted in the investigation of patients with postural hypotension.

Adult↗