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Biomedical subjects

E Salazar

Publications and source records attributed to E Salazar.

At least 19 recordsLinked to original sources

Effects of whisker trimming on GABA(A) receptor binding in the barrel cortex of developing and adult rats.

Both sensory deprivation and blockade of gamma-aminobutyric acid A (GABA(A)) receptors result in signs of cortical disinhibition. To investigate whether down-regulation of GABA(A) receptors could underlie effects of sensory deprivation, [3H]muscimol binding was assessed in rat whisker barrels after chronic whisker trimming. Vibrissae in row C or rows A,B,D, and E were trimmed during certain developmental periods. When whiskers were trimmed for the first 6 postnatal weeks, [3H]muscimol binding was 8.3% lower in deprived barrel rows than in adjacent nondeprived rows (P < 0.001). The effect may be somewhat selective for GABA(A) receptors because there was no evident change in N-methyl-D-aspartate (NMDA) receptors as indicated by [3H]MK-801 binding. Ten weeks after whiskers were allowed to regrow, the decrease in [3H]muscimol binding was partly reversed (P < 0.002), leaving a 3.3% decrease (P < 0.001). These declines in GABA(A) receptors could contribute to persisting electrophysiological signs of reduced inhibition in similarly deprived barrel neurons (Simons and Land [1987] Nature 326:694-697). A 6-week deprivation beginning in adulthood resulted in a 7.7% decrease (P < 0.001), indicating that the effect is not restricted to an early critical period. In rats trimmed for the first 10 postnatal days, [3H]muscimol binding declined 2.3% (P < 0.05), which is a small change compared with the magnitude of the developmental peak; thus, normal whisker input apparently is not required for the developmental increase in GABA(A) receptors. The present study suggests that sensory input can regulate cortical GABA(A) receptors in adulthood and during ontogeny. Down-regulation of cortical GABA(A) receptors may be a compensatory mechanism that serves to disinhibit the reduced sensory input.

Aging

Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia.

OBJECTIVE: To determine the incidence of antimicrobial-resistant, nonpathogenic Escherichia coli among healthy children aged 6-72 months in Camiri town and a rural village, Javillo, in south-eastern Bolivia. METHOD: A community-based survey: stool samples were obtained from 296 healthy children selected by modified cluster sampling in Camiri and all 25 eligible children in Javillo. E. coli isolates were tested for antimicrobial susceptibility according to the standard disc diffusion method. By a questionnaire survey of 12 pharmacies and by using simulated patients, we investigated the antimicrobial availability and the usage patterns in Camiri town. RESULTS: In Camiri, over 90%, and in Javillo over 70% of children carried E. coli resistant to ampicillin, trimethoprim-sulphamethoxazole (TMP/SMX) or tetracycline. Overall, 63% of children carried E. coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and chloramphenicol. In the simulated patients study, antimicrobials were dispensed inappropriately for 92% of adults and 40% of children with watery diarrhoea, and were under-prescribed for males with urethral discharge (67%) or females with fever and dysuria (58%). The dose and/or duration of antimicrobials dispensed was almost always too low. CONCLUSION: Our study showed a disturbingly high prevalence of carriage of nonpathogenic E. coli resistant to antimicrobials. The prevalence of resistance to ampicillin and TMP/SMX was higher than that previously reported in developing countries. The existence of a large reservoir of resistance genes in healthy individuals in developing countries represents a threat to the success of antimicrobial therapy throughout the world. Programmes to improve rational and effective drug use in developing countries are urgently needed.

Adult

Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses.

OBJECTIVES: This report describes our experience with the use of an anticoagulant regimen of adjusted doses of subcutaneous heparin during pregnancy in women with cardiac valve prostheses. BACKGROUND: Gravid patients with prosthetic heart valves require long-term anticoagulant therapy. To avoid the increased incidence of fetal morbidity and mortality associated with the use of coumarin agents in such patients during pregnancy, anticoagulation with subcutaneous heparin has been suggested. Controversy exists concerning the appropriate treatment of these patients. METHODS: Forty pregnancies in 37 women with prosthetic heart valves were prospectively followed up. Subcutaneous heparin was administered from the 6th until the end of the 12th week and in the last 2 weeks of gestation. Heparin was given every 8 h in the first 36 cases and every 6 h in the last 4 cases, and the dose adjusted to maintain the activated partial thromboplastin time at 1.5 to 2.5 times the control level. Acenocoumarol was used at other times. RESULTS: The incidence rate of spontaneous abortions was 37.5%; there was one neonatal death (2.5%) due to cerebral hemorrhage. No signs of coumarin-induced embryopathy were found in any of the 16 live-born infants studied by the geneticist. One mother died of gastrointestinal bleeding while receiving oral anticoagulant agents. There were two cases of fatal massive thrombosis of a mitral tilting-disk prosthesis during heparin therapy. The study was interrupted after the last of these two cases. CONCLUSIONS: The regimen of adjusted doses of subcutaneous heparin used in this study is not effective to prevent thrombosis of mechanical valve prostheses during pregnancy. The use of heparin from the 6th to the 12th week of gestation does not decrease the high incidence of fetal wastage associated with anticoagulant therapy. Coumarin agents provide adequate protection against thromboembolism during pregnancy in patients with mechanical valve prostheses.

Abnormalities, Drug-Induced

Safety, immunogenicity, and excretion pattern of single-dose live oral cholera vaccine CVD 103-HgR in Peruvian adults of high and low socioeconomic levels.

Groups of 122 Peruvian adults of low socioeconomic level (SEL) and 125 of high SEL received a randomly allocated 5 x 10(9)- or 5 x 10(8)-CFU dose of CVD 103-HgR live oral cholera vaccine or a placebo. The vaccine was well tolerated. Vibriocidal seroconversions occurred in 78% of high-SEL and 72% of low-SEL subjects who ingested the high dose and in 78 and 49%, respectively, of those who received the low dose.

Administration, Oral

High frequency of coinfecting enteropathogens in Aeromonas-associated diarrhea of hospitalized Peruvian infants.

Rectal swabs from 391 infants less than 18 months of age who were hospitalized with acute diarrhea and from 138 similarly aged healthy infants were examined for the etiologic agents of diarrhea. Aeromonas spp. were recovered from 205 of 391 (52.4%) diarrheic patients, whereas they were recovered from 12 of 138 (8.7%) controls (P less than 10(-11). Among the 205 Aeromonas-positive diarrheic patients, 118 (57.6%) were found to be coinfected with other common enteropathogens. Of the 164 Aeromonas-positive initial diarrheic specimens, 82 (50.0%) had one or more other enteropathogens present; 30 patients were coinfected with rotavirus, 20 with enterotoxigenic Escherichia coli, 16 with Campylobacter spp., 14 with Shigella spp., 13 with enteropathogenic E. coli, 4 with Vibrio spp., 1 with Salmonella spp., and 1 with Plesiomonas spp. of Aeromonas strains from cases compared with that from controls supports an etiologic role for this organism. However, frequent concomitant infections with other well-recognized enteropathogens and a lack of disease correlation with common Aeromonas phenotypes suggest that only a subset of Aeromonas strains may be diarrhea causing and that such strains may be common to several of the existing species.

Aeromonas

Risks of anticoagulant therapy in pregnant women with artificial heart valves.

In an attempt to identify the best treatment for pregnant women with cardiac-valve prostheses who are receiving oral anticoagulants, we studied 72 pregnancies prospectively. In 23 pregnancies (Group I), the coumarin derivative acenocoumarol was discontinued and the patients received 5,000 U of subcutaneous heparin every 12 hours from the 6th to the 12th week of gestation, in 12 pregnancies (Group II), heparin was not substituted for the coumarin derivative until after the 7th week, and in 37 pregnancies, detected after the first trimester (Group III), the coumarin derivative was given throughout gestation. In most patients heparin was again substituted for the oral anticoagulant after the 38th week. Three mothers had thrombosis of a tilting-disk mitral prosthesis (two cases were fatal) during heparin treatment. No differences were found in the rates of spontaneous abortion in the three groups. Coumarin embryopathy occurred in 25 percent and 29.6 percent of the pregnancies in Groups II and III, respectively. We conclude that in the second and third trimesters of pregnancy, coumarin derivatives provide effective protection against thromboembolism while causing few fetopathic effects, but that these agents are contraindicated from the 6th to the 12th weeks of gestation. Low-dose heparin does not protect against prosthetic-valve thrombosis, and the possibility that a larger dose might be more effective requires further exploration.

Abnormalities, Drug-Induced

Copper distribution in the normal human brain.

Copper concentration was determined in samples from 38 areas of 7 normal human brains. The grey matter contained higher concentrations of copper than the white matter. Identical areas of the grey and white matter of the cerebral cortex showed significant differences between individuals. In the caudate nucleus the highest concentrations of copper were found in the tail followed by the body and the head, respectively. A negative linear regression between age and brain copper levels was demonstrated.

Adolescent

The problem of cardiac valve prostheses, anticoagulants, and pregnancy.

To assess the maternal and fetal risks in patients with cardiac valve prostheses, a series of 223 pregnancies in 156 women was studied. In 68 pregnancies (group I) treatment with antiplatelet agents was substituted for that with coumarinics from the first trimester on. Group II (128 pregnancies) received coumarinics through the thirty-eighth week of gestation. Three patients in group I died as a result of thrombosis of their caged-ball valves. The incidence of cerebral embolism was 25.0% in group I and 2.3% in group II patients, while that of spontaneous abortion was 10.3% and 28.1%, respectively. Coumarin embryopathy was found in 7.9% of group II infants. Fetal death did not occur in the 12 cases in which subcutaneous heparin was substituted for the coumarin derivative in the first trimester and the last 2 weeks of pregnancy (group III), but maternal cerebral embolism developed in 8.3% of the patients. Finally, uneventful pregnancies and deliveries were observed in 12 of 15 mothers (group IV) with biological prostheses who received no anticoagulants. It is concluded that (1) women with cardiac valve prostheses should be counseled against becoming pregnant, (2) antiplatelet agents do not provide protection against thromboembolism in these patients, (3) because of the high incidence of fetal death and birth defects use of coumarinics is contraindicated in the first trimester and the last weeks of pregnancy, (4) the substitution of heparin at these times may decrease the incidence of these complications, and (5) bioprostheses are indicated in women who wish to bear children.

Acenocoumarol

Beliefs regarding the etiology and treatment of infantile diarrhea in Lima, Peru.

Three groups of women in Lima, Peru, were interviewed regarding their beliefs about the etiology and treatment of infantile diarrhea. The first group consisted of 91 mothers of children under the age of 2. These were interviewed at two locations: the pediatric emergency service of a teaching hospital serving northern Lima and a health center located in one of the rapidly growing shantytowns surrounding Lima. The second group consisted of 25 women interviewed in their homes in several shantytowns. Answers given by mothers in both groups were similar. All women were of low socioeconomic status. The third group consisted of 23 adolescent girls and young women interviewed briefly at two schools in Lima. Results of the interviews confirm that diarrhea is not seen as an infectious disease. Instead, it is placed within the framework of the hot--cold dichotomy prevalent in Latin America; diarrhea is believed to be caused by invasion of the body by cold or by ingestion of foods designated as being 'cold'. Suspension of milk feeding is also thought to be an essential part of treatment, a finding of importance in view of the decline in breastfeeding.

Adolescent

The regional distribution of manganese in the normal human brain.

The concentration of manganese per gram dry tissue weight was determined in samples from 39 areas of 8 normal human brains. Manganese was shown to be unevenly distributed with the largest concentrations in the pineal gland and the olfactory bulb. The gray matter yielded a higher content of manganese than the white matter. Significant differences between individuals were found for identical areas of the gray and white matter of the cerebral cortex. Higher levels of manganese were demonstrated in the tail of the caudate nucleus than in the body and the head of the same structure. No significant correlation was shown between the amount of manganese in brain and age.

Adolescent

Comparative genotoxic effects of the cooked-food-related mutagens Trp-P-2 and IQ in bacteria and cultured mammalian cells.

As part of a major study to evaluate the mutagenicity of chemicals produced during the cooking of foods, we examined the responses of bacteria and cultured Chinese hamster cells to the compounds Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole) and IQ (2-amino-3-methylimidazo[4,5-f]quinoline), constituents identified in cooked beef and fish. In the Ames/Salmonella tester strain TA1538, both compounds were confirmed to be extremely potent mutagens that were active at levels below 1 ng/plate in the presence of hamster-liver S9 microsomal fraction. 50-fold higher doses of both compounds were required for mutagenicity in the uvr+ tester strain TA1978. Trp-P-2 also behaved as a strong mutagen in CHO cells using the standard exogenous activation with hamster-liver S9 fraction. At concentrations below 1 microgram/ml it produced dose-dependent increases in cell killing, mutations at the hprt and aprt loci, sister-chromatid exchanges, and chromosomal aberrations. An excision-repair-deficient strain was about 2-fold more sensitive than the normal CHO cells with respect to these genotoxic effects of Trp-P-2. IQ had unexpectedly weak activity for all genetic endpoints in the CHO cells, and it produced clear-cut responses only in the repair-deficient cells and only above a concentration of 10 micrograms/ml. The toxicity that was observed with IQ was not affected by the repair capacity of the cells and was not associated with chromosomal aberrations, indicating that damage to cellular structures other than nuclear DNA was likely the predominant pathway for cell killing. Because the culture conditions normally used for CHO cell exposure were shown to be competent in producing bacterial mutagenicity with IQ, it was concluded that the active metabolite of IQ was present in the medium but was somehow ineffective in reaching the DNA of CHO cells and/or reacting with it. These results suggest that the relative mutagenic potency of compounds in Salmonella may bear no direct relationship to relative mutagenicity in CHO cells, emphasizing precaution in attempting to extrapolate microbial data to mammalian somatic cells. This study illustrates the use and merits of a multi-endpoint assay for genetic damage in CHO cells, the utility of using CHO cells that are defective in excision repair of DNA, and the importance of comparative testing between bacterial and mammalian systems.

Animals

Lipids and lipoproteins in subjects at 1,000 and 3,500 meter altitudes.

To assess the relationship between altitude, atherogenic, and anti-atherogenic lipoprotein cholesterols (low- [C-LDL] and high [C-HDL] density lipoprotein cholesterols, respectively), 136 and 94 Venezuelan Mestizos living at 1,000 and 3,500 in elevation were studied. The two groups did not differ in regard to height, weight, ethnic origin, social or economic status, nutritional patterns, age, or occupation. Both groups had a high level of daily physical exertion, an imperative in their subsistence rural agricultural economy. Due to the mountainous terrain, high altitude residents were thought to have increased levels of physical activity. Males and females at high altitude had significantly lower plasma total cholesterol and C-LDL levels, and slightly lower C-HDL levels than those at low altitudes. It is speculated that reduced coronary heart disease event rates at high altitude might be related to lower levels of the atherogenic lipoprotein cholesterol, C-LDL.

Adult

Mutagenic and toxic activity of environmental effluents from underground coal gasification experiments.

Using bacterial bioassays, we have screened for the presence of mutagens and toxins in extracts from groundwater, and in tar from product gas, at the sites of two Lawrence Livermore National Laboratory (LLNL) in situ experiments: Hoe Creek II and Hoe Creek III. The sites exhibited different potential biological hazards, suggesting that different gasification processes may represent different human health concerns. We found that mutagens are present in groundwater, persist for at least 2 yr after gasification has been terminated, and show a change in activity with time-possibly in parallel with changes in chemical composition. Preliminary evidence suggests that the mutagens in groundwater are quinoline and aniline derivatives, while the toxins in groundwater may be phenolic compounds. In tar from the product gas, the organic bases and neutrals were found to be genotoxic in both bacterial and mammalian cells; the neutral compounds appear to be the major mutagenic health hazards. Neutral compounds constitute most of the tar (85-97 wt%) and were mutagenic in both the bacterial and mammalian cell assays. Tar in the gas stream may be a problem for the aboveground environment if gas escapes through fractures in the overburden. Because it is mutagenic and induces chromosomal damage to mammalian cells, the tar may represent a disposal problem as well. However, it is difficult to assess tar quantitatively as a health hazard because its mutagenic activity is low, possibly due to contaminants in the neutral fraction that act to suppress mutagenicity.

Animals

[Treatment of supraventricular paroxysmal tachycardia and auricular flutter by auricular stimulation].

Although the management of supraventricular tachycardias (SVT) and atrial flutter (AF1) with drugs or cardioversion is usually effective, their use in the high risk patient commonly digitalized, may be dangerous. Since the availability of an alternate therapeutic method is desirable, the usefulness of atrial pacing was evaluated in 31 episodes of tachyarrhythmia in 31 patients with varied heart conditions. The arrhythmia diagnosis and the stimulation were done through a right atrial electrode. In most cases the rate of stimulation was higher than that of the atria (up to 400 stimuli per min). Of 17 cases with SVT (four with preexcitation syndrome), pacing led to sinus rhythm (SR) in all, even though it was transient in two. SR was obtained in six of eleven cases of AF1, through a short lasting atrial fibrillation (AF) in three of them. Four patients with paroxysmal atrial tachycardia with A-V block changed to AF. SR was achieved shortly after termination of the procedure in two of the latter. It is concluded that atrial pacing is a valuable therapeutic method since it is effective, it has very low risk specially in digitalized patients, its does not require anesthesia and because it may be used repeatedly in case of recurrence. The technique of atrial pacing permits, in some cases, the identification of the mechanism responsible for the arrhythmia.

Adolescent

[Correlation between exercise test and coronariography].

In order to evaluate the sensibility and specificity of the maximal treadmill exercise-stress test, a correlation was made, in fifty patients, of the resus of the test and the findings at selective coronary arteriography. None of the patients had received cardioactive drugs previous to the study. Among twenty-nine patients with proven coronary disease, three had false negative exercise tests. The remaining twenty-six cases had positive tests. The sensitivity of the method (reliability in identifying the presence of disease) was 89.7%. Twelve of twenty-one subjects with normal coronary arteries had negative exercise tests. In eight patients without coronary artery lesions, the exercise test was positive (false positive tests). An additional patient had an equivocal response and is included among the false positive responses. These nine-patients form a special group since they had severe heart disease, even though it was not due to atherosclerosis of the major coronary vessels. The specificity of the test (reliability in identifying the absence of disease) was 57.1%. However, in the absence of other heart disease, none of the subjects with normal coronary arteries had a false positive response. An analysis is made of the possible causes of these false negative and false positive responses. It was also shown in this study that the patients with coronary artery disease and positive treadmill tests had a definite functional aerobic impairment as well as a significant reduction in such indices of myocardial oxygen consumption as the heart rate and the double product (pressure-pulse), when compared to the subjects with normal coronary vessels and negative tests. In the group of patients with false positive responses, these parameters were not significantly different from the normals. The exercise-stress test protocol used in this study appears to have an adequate sensibility and an acceptable specificity.

Adult