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Biomedical subjects

J Villar

Publications and source records attributed to J Villar.

At least 19 recordsLinked to original sources

Predictive ability of meta-analyses of randomised controlled trials.

Although meta-analysis of randomised clinical trials is increasingly used, the evaluation of its ability to predict the results of large trials is not available. We have calculated the relative risks (and 95% confidence intervals) for thirty meta-analyses of different interventions in perinatal medicine, covering 185 randomised controlled trials, but with the largest trial removed. We then compared those results with the result of the largest trial (total sample size more than 1000) done on that intervention and outcome. Twenty-four meta-analyses correctly predicted the direction of the treatment effect, but only eighteen of the thirty were the same both in direction of treatment effect and in statistical significance as the largest trial. There was moderate agreement, beyond chance, between meta-analysis and largest trial results (kappa statistic 0.46-0.53). A meta-analysis demonstrating a protective effect from an intervention of more than 40% had a 60% probability of correctly predicting results of the same magnitude of the largest trial. Researchers and funding agencies may use meta-analysis before recommending a clinical practice or to summarise results of three controlled trials before deciding on additional studies of promising interventions. However, further evaluation of the meta-analytical method is needed if the qualitative and quantitative results it yields are to be better understood.

Confidence Intervals

Impact of health education during pregnancy on behavior and utilization of health resources. Latin American Network for Perinatal and Reproductive Research.

OBJECTIVE: Our purpose was to assess whether an intervention in the education of the mother and the support person involves a change in health-related behavior and use of health facilities. STUDY DESIGN: A randomized, controlled trial was conducted in four cities of Latin America on pregnant women at risk. Half of them (n = 1115) received a home intervention of four to six visits dealing with psychosocial support and education about health-related habits, alarm signs, hospital facilities, antismoking and antialcohol programs, and a reinforcement of adequate health services utilization for the pregnant woman and a support person. The control group (n = 1120) received routine prenatal care. RESULTS: The distribution of risk factors and demographic, obstetric, and psychologic characteristics at baseline was similar in both groups. Women in the intervention group showed a statistically significant better knowledge of seven of the nine alarm signs considered and of two of the three labor-onset signs required. No differences between groups were observed in improvement on diet, cigarette and alcohol consumption, maternal physical strain, lactation at 40 days postpartum, and utilization of health facilities. CONCLUSIONS: An intervention of psychosocial support and health education during pregnancy failed to show any benefit on perinatal outcome, health-related behavior, or utilization of health facilities.

Alcohol Drinking

Transbilayer movement of erythrocyte membrane cholesterol in human essential hypertension.

OBJECTIVE: To study whether the rate of transbilayer movement of membrane cholesterol is impaired in erythrocyte membrane of normo- and hypercholesterolaemic patients with untreated essential hypertension. DESIGN: An observational case-control study. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The rate of transbilayer movement of membrane cholesterol was monitored in intact erythrocytes, using a radiolabelled cholesterol tracer. Erythrocytes were treated briefly or continuously with cholesterol oxidase to convert a portion of the outer leaflet cholesterol to cholestenone, and the specific radioactivity of cholestenone was determined over the period of tracer equilibration. The decrease in specific radioactivity of cholestenone reflected the transbilayer movement of radiolabelled cholesterol. RESULTS: There were no significant differences between the diffusion of cholesterol across the erythrocyte membrane of normo- and hypercholesterolaemic hypertensive patients, but the rates were significantly lower than that estimated in control subjects. The mean +/- SD half-times for the process were 55.1 +/- 8.8 and 11.3 +/- 2.1 min in controls, 63.1 +/- 9.2 and 15.8 +/- 2.3 min in normocholesterolaemic hypertensive patients, and 66.2 +/- 9.4 and 16.2 +/- 1.7 min in hypercholesterolaemic hypertensive patients, after a brief and after a continuous cholesterol oxidase treatment, respectively. CONCLUSION: There is a reduction in the transbilayer movement of membrane cholesterol in erythrocytes of patients with untreated essential hypertension.

Adult

Induction of the stress response to prevent organ injury.

Septic shock, multiorgan dysfunction, and the acute respiratory distress syndrome are major contributors to morbidity and mortality in the ICU setting. Animal studies have shown that these forms of injury can be attenuated or prevented if a phenomenon, called the stress response, is activated. The stress response, characterized by a transient downregulation of most cellular products and by the upregulation of the heat-shock proteins (HSPs), has been shown to provide protection to cells and experimental animals if triggered prior to an otherwise lethal injury. The mechanisms by which the stress response is protective are not known with certainty, but HSPs appear to play an important role. HSPs are constitutively present in all cells studied to date and can also be induced by artificial fever and by nonthermal means. They act as molecular chaperones, interacting transiently with newly synthesized proteins and proteins experiencing difficulty in proper folding. HSPs also escort and help proteins to cross membranes. This chaperone function is essential for cellular protection since it provides a mechanism by which defective polypeptides may be directed to lisosomes for degradation. This article summarizes the current literature on the effects of the stress response in protecting cells and animals from lethal forms of systemic and organ damage.

Animals

[Influences of hyperinsulinemia in the lipid profile of hypertensive patients].

BACKGROUND: Hypertension and dyslipemia are associated with a greater frequency than that randomly expected. The increase in insulinic resistance hyperinsulinemia is one of the factors implicated in the pathogenesis of this association. In the present study the lipid profile of hypertensive patients is analyzed according to the degree of insulinemia. METHODS: The lipid profile (total cholesterol, fraction linked to low density lipoproteins cLDL, high density cHDL, triglycerides and plasma apolipoproteins A1 and B were determined in 87 patients with essential high blood pressure. Moreover an oral overdose of 75 g of glucose was administered with determinations of glycemia, insulinemia and C peptide at the time of glucose administration, 60 and 120 minutes. RESULTS: Upon separation of the hypertense patients into two groups according to the insulinemia achieved following an oral overload of glucose, those hypertensives with a greater degree of insulinemia showed a significant increase in triglycerides (p < 0.05) and also a significant decrease in cHDL (p < 0.001). The hypertensive patients with lower insulinemia showed a significant increase in total cholesterol (p < 0.05) and fraction linked to LDL although the latter was not significant. CONCLUSIONS: Two different lipid profiles may be observed in hypertensive patients: one linked to hyperinsulinemia and characterized by an increase in triglycerides and a decrease in cHDL and another with no relation with hyperinsulinemia which is manifested by an increase in total cholesterol and cholesterol transported by the LDL.

Adult

Ambulatory blood pressure monitoring in physicians working in a hospital: is there an increase in the number of subjects with high workplace blood pressures?

Sixty-two physicians from our hospital who were normotensives, as supported by casual blood pressure measurements, underwent 24-h blood pressure monitoring which included their normal work, home rest and sleep periods. During working hours, 19% of the subjects showed mean diastolic and/or diastolic plus systolic blood pressures higher than those admitted as normal by the WHO for casual measurements for out of work subjects. Both mean systolic and diastolic blood pressure measurements, during the work at the hospital, were significantly higher in males (P < 0.01 and P < 0.005, respectively) than the mean of the readings obtained during the 24-h period, but this phenomenon did not occur among the females. Male's mean systolic (129.8 +/- 10.6 vs. 117.1 +/- 9.7 mmHg, P < 0.0001) and diastolic pressures (83.4 +/- 8 vs. 74.9 +/- 7.3 mmHg, P < 0.001) were significantly higher during the working period in relation to those of the female group. Discussing the influence of the kind of work on blood pressure, we came to the conclusion of the existence in our environment of a group of subjects (generally males), presenting high blood pressure values during their working period at the hospital and normal or borderline values during the rest of the day. This should be of interest, since it has been reported that subjects with high workplace blood pressure have an increased risk of hypertension and target-organ damage.

Adult

The Latin American Multicenter Trial on psychosocial support during pregnancy: methodology and baseline comparability. Latin American Network for Perinatal and Reproductive Research (LANPER).

This article presents the methodology and baseline findings of a large multicenter trial involving four countries from Latin America (Argentina, Brazil, Cuba, and Mexico). The study was a randomized, controlled, single-masked trial to investigate the impact of social support during pregnancy on perinatal outcomes. Pregnant women with gestational ages between 15 and 22 weeks were screened in health facilities in the four countries. Those presenting with one or more risk factors for having a low-birthweight baby were invited to join the trial. A total of 2235 women--between 500 and 600 in each country--were randomized into an intervention (n = 1110) or a control (n = 1125) group. Both groups were comparable in terms of nearly all baseline variables. The intervention group received a minimum of four visits at home by a trained health worker who provided direct emotional support, health education, and an attempt to enhance the woman's social support network. Over 90% of all women were evaluated at 36 weeks of pregnancy and soon after delivery, and 85% at the 40th day postpartum. The outcomes under study included intrauterine growth retardation, gestational age, perinatal and maternal morbidity and mortality, labor interventions, psychological distress and characteristics of the social support network, among others. This trial showed that it was possible to select, screen, randomize, visit, and evaluate a large number of women in four Latin American countries using a standardized methodology.

Adolescent

The measurement of diastolic blood pressure during pregnancy: which Korotkoff phase should be used?

OBJECTIVE: The aim of this study was to compare the two Korotkoff phases, to estimate diastolic blood pressure during pregnancy. STUDY DESIGN: A cohort of 1194 nulliparous pregnant women were followed up prospectively from the twentieth week of pregnancy until delivery. Blood pressure measurements were obtained with random-zero sphygmomanometers at 20, 23, 25, 27, 31, and 35 weeks and then weekly until delivery. After 10 minutes of rest five blood pressure measurements were obtained in each position: supine, lateral, and seated. Korotkoff phases IV and V were obtained in each measurement. RESULTS: The frequency of 0 values was always < 0.5% (n = 10,501 in each time and position). Mean differences between both phases throughout pregnancy fluctuates around 6 mm Hg. Minor differences (mean 3.7 mm Hg) without outlier values were observed in women with diastolic hypertension. Phase 5 showed a better association with other outcome variables related to hypertension, such as proteinuria, intrauterine growth retardation, and hyperuricemia. CONCLUSION: Considering that phase 5 is easier to obtain, its use implies very few 0 values, that the difference between the two Korotkoff phases is around 6 mm Hg, and that the association with hypertension-related complications is similar to that of phase 4.

Blood Pressure

Sodium arsenite induces heat shock protein-72 kilodalton expression in the lungs and protects rats against sepsis.

OBJECTIVE: To examine the hypothesis that induction of heat shock proteins by a nonthermal mechanism would confer protection against experimental sepsis. DESIGN: Prospective, blind, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Sixty-two adult male Sprague-Dawley rats (weight range 250 to 350 g). INTERVENTIONS: Administration of sodium arsenite or saline in an animal model of sepsis by cecal ligation and perforation. MEASUREMENTS AND MAIN RESULTS: Sixty-two rats were randomly divided into two groups: group 1 received sodium arsenite (6 mg/kg iv) and group 2 received saline injection, in a blinded fashion. Eighteen hours after receiving sodium arsenite or saline, cecal ligation and perforation were performed and the animals were monitored for mortality for 96 hrs. Sodium arsenite injection, in the absence of an increase in body temperature, induced heat shock protein of 72-kilodalton molecular weight expression in the lung, which was detected 2 hrs after injection, peaked between 9 and 24 hrs, and returned to baseline by 48 hrs. Prior administration of sodium arsenite conferred significant protection against cecal ligation and perforation-induced mortality at 18 hrs (p = .002) and 24 hrs (p v .026) after cecal ligation and perforation, and correlated with expression of heat shock proteins in the lungs. However, at 48 and 96 hrs, when heat shock protein expression returned to basal values, the mortality rates of both groups were indistinguishable. CONCLUSIONS: We conclude that in vivo injection of sodium arsenite induces expression of HSP-72 in the lungs, and confers transient protection against experimental sepsis during the period that heat shock proteins are also expressed.

Animals

Intrauterine growth retardation: fluctuation of fetal pH measured between beginning and at the completion of labor.

UNLABELLED: The aim of this study was to evaluate the fluctuation of fetal pH in blood samples taken at the beginning of labor and at the moment of birth as related to intrauterine growth retardation syndrome. This is a prospective follow-up of term gestations, of which 41 were diagnosed as intrauterine growth retardation (IUGR) and 61 as normal ones. pH was measured in scalp blood sample at the beginning of the labor and in umbilical artery right after birth in both groups respectively. The rate of decrease of pH value in relation to duration of labor was determined for each case. Our results are: 1) Lower baseline pH were found in the IUGR group (pH 7.32 vs 7.34, p < 0.01), lower arterial blood pH at birth/.23 +/- 0.08 vs 7.27 +/- 0.08, p < 0.05). 2) Faster decrease of the pH during the labor (0.019 unit/hour vs 0.012, p < 0.05) as related to IUGR. CONCLUSION: IUGR fetuses are more acidotic at the beginning of the labor, and the rate of decrease of the fetal pH per unit of time during the labor is faster at least in a theoretical situation nevertheless it will require more studies if any practical applications are thought of.

Acidosis

Distribution of erythrocyte membrane cholesterol in human essential hypertension.

OBJECTIVE: To determine whether the cholesterol distribution is impaired in erythrocyte membranes of normo- and hypercholesterolaemic patients with untreated essential hypertension. DESIGN: Observational case-control study. METHODS: Erythrocytes were prepared from venous blood samples obtained from normotensive subjects and hypertensive patients. The membrane cholesterol distribution was measured by cholesterol oxidation to cholestenone after continuous cholesterol oxidase treatment. The membrane cholesterol content was determined. The ability of cells to be labelled with [3H]-cholesterol was also tested. RESULTS: The cholesterol distribution was asymmetric in erythrocyte membranes of the control subjects, and hypertensive patients. The oxidation rate was faster in normotensive subjects, and no differences were found between normo- and hypercholesterolaemic hypertensive patients. Total cholesterol mass was lower in erythrocyte membranes of hypertensive patients, as indicated by a higher incorporation of radioactive cholesterol. CONCLUSION: These data suggest that the membrane cholesterol distribution is impaired in patients with untreated essential hypertension, and support the presence of cholesterol-rich domains in the erythrocyte membrane inner monolayer.

Adult

Induction of the heat shock response reduces mortality rate and organ damage in a sepsis-induced acute lung injury model.

OBJECTIVE: To test the hypothesis that induction of heat shock proteins before the onset of sepsis could prevent or reduce organ injury and death in a rat model of intra-abdominal sepsis and sepsis-induced acute lung injury produced by cecal ligation and perforation. DESIGN: Prospective, blind, randomized, controlled trial. SETTING: University research laboratory. SUBJECTS: One-hundred forty-two adult Sprague-Dawley rats (weight range 200 to 300 g). INTERVENTIONS: Production of intra-abdominal sepsis and exposure to heat stress. Animals were randomly divided into four groups: heated and septic, heated and sham-septic, unheated and septic, and unheated and sham-septic. MEASUREMENTS AND MAIN RESULTS: We evaluated the mortality rate and pathologic changes in lung, heart, and liver at 18 hrs after cecal perforation, at 24 hrs after removal of the cecum, and at 7 days after perforation. Heated animals exhibited a maximum increase in heat shock protein of 72 kilodalton molecular weight protein concentrations in the lungs and heart 6 to 24 hrs after the hyperthermic stress. By 18 hrs after perforation, 25% of the septic, unheated animals had died whereas none of the septic heated animals had died (p < .005). Septic, heated animals showed a marked decrease in 7-day mortality rate (21%) compared with septic unheated animals (69%) (p < .01). Furthermore, septic heated animals showed less histologic evidence of lung and liver damage than septic unheated animals. CONCLUSIONS: These data suggest that thermal pretreatment, associated with the synthesis of heat shock proteins, reduces organ damage and enhances animal survival in experimental sepsis-induced acute lung injury. Although the mechanisms by which heat shock proteins exert a protective effect are not well understood, these data raise interesting questions regarding the importance of fever in the protection of the whole organism during bacterial infection.

Animals

Cell membrane fatty acid composition in type 1 (insulin-dependent) diabetic patients: relationship with sodium transport abnormalities and metabolic control.

We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids (19.0% +/- 2.2 vs 24.6% +/- 1.4, p < 0.0001) mainly at the expense of docosahexaenoic acid C22:6(n3) (2.9% +/- 1.1 vs 5.3% +/- 1.3, p < 0.001), and arachidonic acid C20:4n6 (12.0% +/- 1.6 vs 15.1% +/- 0.6, p < 0.0005). Conversely, the total amount of saturated fatty acids was significantly increased (p < 0.05) and the polyunsaturated/saturated ratio was decreased in the Type 1 diabetic patients (p < 0.00 005). Neither the time from diagnosis, nor C-peptide levels, correlated with parameters indicating a poor metabolic control of Type 1 diabetes. However, C22:6(n-3) and total n-3 content significantly correlated with HbA1c (r = -0.79 and r = -0.88, respectively, p < 0.01), fructosamine (r = -0.71 and r = -0.74, respectively, p < 0.05), and Na+-K+ ATPase activity (maximal rate/Km quotient) (r = 0.78 and r = 0.71, respectively, p < 0.05). In conclusion we have found marked alterations of cell membrane lipid composition in Type 1 diabetic patients. These cell membrane abnormalities in lipid content were related to sodium transport systems and to poor metabolic control. Either diet, or the diabetic state, might be responsible for the observed cell membrane abnormalities. A dietary intervention study might differentiate the role of diet and diabetes in the reported cell membrane alterations.

Adult

The Latin American trial of psychosocial support during pregnancy: a social intervention evaluated through an experimental design.

Perinatal health problems are a public health priority in Latin America. Among the identified risk factors, psychological and social conditions play a crucial role. However, care during pregnancy and delivery in the region is usually hospital-centered and does not address women's psychological and social conditions. The preeminence of research on perinatal health, along with the necessity for testing interventions that represent alternative models to improve women's health, gave the Latin American Network for Perinatal and Reproductive Research grounds to develop a multicenter randomized controlled trial to evaluate a program of social support and health education during pregnancy. The conceptual framework for this study was based on an ecological model of social support, i.e. a model in which social support and health education play a synergistic role and are meant to modify stressful situations and negative health-related behaviors. The target population consisted of women attending obstetric hospitals before the 22nd gestational week, at high psychological and social risk (n = 2236). The intervention consisted of four to six home visits, carried out by social workers, and had four main components: the reinforcement of pregnant women's social support network, emotional support, health education, and the improvement of health services utilization. The main foci of the intervention were determined after an ethnographic study was carried out to identify stress-producing situations and needs for support during pregnancy. Besides the home visits, the program also offered a hot-line, an office in the hospital, a specially designed poster and booklet, and a 'guided tour' of the health institution. Since this was a multicenter trial, the program's standardization was a crucial methodological aspect that was achieved through the training course for the home-visitors team. Biological and psychosocial outcomes were measured in both experimental and control groups at the 36th week of gestational age, post-partum and at the 40th day after delivery. The attributes of the multicenter population showed an important variability, reflecting differences in the countries or hospitals' population prevalent attributes. The results of the program's implementation were analyzed, demonstrating that home visitors adapted topics discussed during the interviews to the women's conditions and the stage of pregnancy during which the visit took place.(ABSTRACT TRUNCATED AT 400 WORDS)

Female

Effects of induced hypothermia in patients with septic adult respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that treatment with hypothermia affects the course of overwhelming acute respiratory failure associated with sepsis. DESIGN: Concurrent-controlled, prospective study. SETTING: Adult multidisciplinary ICU in a teaching hospital. PATIENTS: Nineteen consecutive patients with septic ARDS mechanically ventilated and a P(A-a)O2 > 500 Torr during 36 h on > or = 10 cm H2O of PEEP. INTERVENTIONS: Patients were assigned to receive conventional treatment (n = 10) or conventional treatment plus mild hypothermia (32-35 degrees C) instituted as a last resort (n = 9). RESULTS: Hypothermia (33.7 +/- 0.6 degrees C) was associated with a reduction in mortality rate (67% vs. 100%, P < 0.05), P(A-a)O2 (P < 0.001), heart rate (P < 0.001), cardiac index (P < 0.01), and QS/QT (P < 0.01). There were no significant differences in oxygen consumption (VO2) before (243 +/- 74 ml/min) and during treatment with hypothermia (246 +/- 87 ml/min) although O2 extraction increased during hypothermia (26 +/- 6 vs. 30 +/- 6%, P < 0.05). CONCLUSIONS: This study suggests that hypothermia was effective in improving oxygenation and survival in patients with severe ARDS associated with sepsis, even though VO2 was unchanged.

Adult