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Biomedical subjects

R Salas

Publications and source records attributed to R Salas.

16 recordsLinked to original sources

Venezuelan haemorrhagic fever.

An outbreak of severe haemorrhagic illness began in the municipality of Guanarito, Portuguesa State, Venezuela, in September, 1989. Subsequent detailed study of 15 cases confirmed the presence of a new viral disease, designated Venezuelan haemorrhagic fever. Characteristic features are fever, toxicity, headache, arthralgia, diarrhoea, conjunctivitis, pharyngitis, leucopenia, thrombocytopenia, and haemorrhagic manifestations. Other features include facial oedema, cervical lymphadenopathy, nausea/vomiting, cough, chest or abdominal pain, and convulsions. The patients ranged in age from 6 to 54 years; all were residents of rural areas in central Venezuela, and 9 died. Infection with Guanarito virus, a newly recognised arenavirus, was shown by direct culture or by serological confirmation in all cases. Epidemiological studies suggest that the disease is endemic in some rural areas of central Venezuela and that it is rodent-borne. Venezuelan haemorrhagic fever has many similarities to Lassa fever and to the arenavirus haemorrhagic fevers that occur in Argentina and Bolivia.

Acute Disease

Evidence for direct coupling of primary agonist-receptor interaction to the exposure of functional IIb-IIIa complexes in human blood platelets. Results from studies with the antiplatelet compound ajoene.

Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro, ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. In this paper we show that ajoene has a unique locus of action, that is not shared by any other known antiplatelet compound. For example, ajoene inhibits agonist-induced exposure of fibrinogen receptors, as well as intracellular responses such as activation of protein kinase C and the increase in cytoplasmic free calcium induced by receptor-dependent agonists (collagen, ADP, PAF, low-dose thrombin). On the other hand, with agonists that can by-pass (at least partially) the receptor-transductor-effector sequence, such as high-dose thrombin, PMA, NaF, only the exposure of fibrinogen receptors is blocked by ajoene. Binding of fibrinogen to chymotrypsin-treated platelets is only slightly inhibited by ajoene. The results reported here also show that: (a) ajoene does not act as a calcium chelator, does not impair the initial agonist-receptor interaction and does not influence the basal levels of intracellular inhibitors of platelet activation such as cyclic GMP; (b) the locus of action of ajoene is a yet unknown molecular step that links, in the case of physiological agonists, specific agonist-receptor complexes to the sequence of the signal transduction system on the plasma membrane of platelets. In the case of non-physiological, receptor-independent agonists (PMA, NaF), we can only speculate on the hypothesis that they somehow mimic the effect of the agonist-receptor complexes on the signal transduction system; and (c) the exposure of fibrinogen receptors is not a direct consequence of other intracellular processes. These observations clearly show, for the first time, that the exposure of fibrinogen receptors is a membrane event proximally and obligatorily coupled to the occupancy of other membrane receptors by their agonists without any intervention by the cytoplasmic biochemical processes. Additional results support the involvement of G-proteins in these early events of platelet activation. Furthermore, a role of the beta tau subunits of G-proteins in the exposure of fibrinogen receptors is proposed.

Antibodies, Monoclonal

Left ventricular aneurysm and intraventricular thrombi. Investigation and surgical correlations.

Formation of a left ventricular aneurysm and intraventricular thrombus represents one of the dreaded sequelae of coronary artery disease and acute myocardial infarction. The present emphasis is to reduce the incidence by reduction of cholesterol and fats, elimination of smoking, improved detection and control of hypertension and diabetes mellitus. Earlier diagnosis is available with stress testing and other noninvasive techniques. Cardiac catheterization allows detection of occlusive lesions. The CASS and other studies increasingly prove that percutaneous angioplasty and coronary artery bypass surgery improve life expectancy and implicitly should reduce the incidence of acute myocardial infarction. In the setting of the latter, thrombolytic agents may reduce the amount of myocardial injury. Despite these measures, formation of left ventricular aneurysms remains a common occurrence. Diagnosis and management are critical issues to the cardiac surgeon.

Cardiac Catheterization

Retinal neurotransmitter interaction as reflected in horizontal cell spatial behaviour.

The effects of 5-hydroxytryptamine (5-HT) and its precursors 5-hydroxytryptophan (5-HTP) and L-tryptophan (L-Tryp) on the spatial properties of horizontal cells were studied in the isolated and perfused retina of the teleost Eugerres plumieri. All three compounds produce a contraction of the receptive field, evaluated by the ratio of responses evoked by local and distant light stimuli. This is the result of cell uncoupling, revealed by the hindrance to diffusion of intracellularly injected Lucifer yellow. Similar effects are produced by dopamine (DA) and the effectiveness is DA much greater than 5-HT greater than 5-HTP greater than L-Tryp. All these effects are blocked by Haloperidol. HPLC studies of endogenous DA release reveal that it occurs when isolated retinas are incubated with 50 mM potassium, 10 microM 5-HT or 5-HTP, but is not found with up to 1 mM L-Tryp. The results indicate that indolaminergic cells induce the release of DA from interplexiform cells, which in turn uncouples horizontal cells in the fish retina.

5-Hydroxytryptophan

Results of emergent versus elective cardiac transplantation procedures.

Twenty-six patients underwent emergent (Group I) and 34 patients elective (Group II) cardiac transplantation (C. Tx.) from June 1985 through June 1989. Age, sex, etiology, presence of diabetes, renal failure and pulmonary artery pressures were comparable for both groups (P greater than 0.5). Twenty-two patients were in New York Heart Association (NYHA) Class IV for Group I and 17 for Group II. Group I included 12 patients on inotropic agents, five on intra-aortic balloon pump (IABP) and one on IABP and cardiopulmonary bypass (CPB). Elective patients were stable at home. Location of the donor heart and mean ischemic times were comparable for both groups. Early mortality (within 30 days) included four patients for Group I and two for Group II. There were four late deaths for Group I patients and six for Group II. Four deaths were due to infection, six to rejection, two to malignancy, two neurological and one each to suicide and multisystem failure. Immunosuppression regimen was similar for both groups. The number and severity of early and late rejection episodes were similar despite blood group crossing in 11 patients for Group I (P less than .01). Incidence of infection was comparable. Favorable lifestyles were comparable, including employment of 12 patients for Group I and 16 for Group II. Cumulative survival for the entire series was 70% at two years. The study indicates that the results of emergent and elective cardiac transplantation procedures are equally gratifying, that mortality is mainly related to rejection and sepsis complications and blood group crossing does not significantly increase the number of rejection episodes.

Bacterial Infections

Cyclic adenosine monophosphate as a second messenger in horizontal cell uncoupling in the teleost retina.

The reduction in the receptive field of horizontal cells of the teleost Eugerres plumieri observed upon dopamine (DA) superfusion is thought to be due to cell uncoupling. The possible mechanisms by which activation of DA receptors modify the electric coupling between horizontal cells were studied in the present work. It was found that the effect of DA in different preparations is mediated by a modification of intracellular concentration of cAMP and H+. The effects of intracellular injection of cAMP and H+ were studied in retinal horizontal cells of the teleost E. plumieri. A triple microelectrode was used to inject the ion iontophoretically, to pass current pulses, and to record voltages from the same cell, while a fourth microelectrode was used to record voltages from a neighboring cell in the same retinal layer. Responses evoked by light spots and annuli were evaluated simultaneously. Coupling ratios between neighboring horizontal cells ranged from 0.22 to 0.45. The intercellular resistance (Rc), 0.5-3.5 x 10(6) ohms, and that of the remaining cell membrane resistance (Rm), 2.5-18 x 10(6) ohms, were calculated by means of a passive electrical model that has a hexagonal array. The microinjection of H+ with injection current from +5 to +30 nA for 40 to 100 sec led to temporary and reversible light response reduction. The coupling ratio between two impaled cells was reduced by about 30%, and intercellular resistance (Rc) increment was 320% while cell membrane resistance (Rm) did not change consistently. There was also a temporary and reversible Rm reduction (70-85%) and an Rc increment of 170-330% when cyclic adenosine monophosphate was iontophoretically injected with current from -30 to -40 nA for 50 to 170 sec. The coupling ratio between two impaled cells was reduced by about 40%, and light responses recorded from the injected cell showed a reduction in amplitude with the same time course as that of the resistive changes. The injection of Lucifer yellow into a horizontal cell under normal conditions always results in pronounced fluorescence for more distant cells; however, under constant injection of H+ or cAMP only the injected cell is fluorescent, which provides direct evidence of the reduction in the effectiveness of coupling between horizontal cells. The observed effects of intracellular H+ or cAMP injection correspond to the resistive changes in Rc and coupling ratio that occur in the horizontal cell network upon superfusion with a dopamine (DA) solution.

Animals

Identification of horizontal cells generating different spectral responses in the retina of a teleost fish (Eugerres plumieri).

Six different types of spectral responses were recorded from horizontal cells under mesopic conditions in perfused retina, isolated from the dark-adapted mojarra (Eugerres plumieri). They were tentatively termed photopic Lr-, Lg1-, Lg2-, Lb-, and C-type, and scotopic L-type. The Lr-, Lg-, and Lb-type responses showed a maximum peak at 605, 550, and 516 nm respectively, while the C-type was composed of hyperpolarizing potentials in response to shorter wavelengths and depolarizing potentials in response to longer wavelengths (so-called R/G-type). The scotopic L-type has a peak at 516 nm in the spectral response and a slow decay phase in the waveform response. Following a brief period of diffuse illumination, it was found that the Lg1-type response is altered to the Lr-type, while both Lg2- and Lb-type responses change to the C-type. Intracellular marking with Lucifer or Procion yellow identified the cellular origins of different response types: external (He) and medial horizontal (Hm) cells for the Lr-type, internal horizontal (Hi) cells for the C-type, and rod-horizontal (Hr) cells for the scotopic L-type. Only He cells were found to possess an axon, while dye coupling was seen between axonless Hm, Hi, or Hr cells but not between He cells. The morphology of these fluorescent dye-marked cells was the same as that of the respective cells observed in Golgi-stained materials.

Animals

Considerations on the possible structrual basis of neuronal integrated functions.

Different types of dendro-dendritic and dendro-somatic contacts in several species are described. They are classified in five varieties: (a) parallel dendro-dendritic contacts; (b) crossed dendro-dendritic contacts; (c) perisomatic interdendritic contacts; (d) perivascular interdendritic contacts; (e) dendro-somatic contacts. It is hypothetically postulated, in agreement with other authors, that the structurally differentiated interdendritic and dendro-somatic contacts could act as functional junctions for the electrotonic spread of stimuli between neighbour neuronal elements.

Action Potentials

The role of surgery in the management of pulmonary monosporosis. A collective review.

Nine cases of pulmonary monosporosis treated in the Missouri State Chest Hospital over a period of 19 years (1956 to 1975) were reviewed. Nine other cases from the literature are summarized. Ten of these 18 patients underwent resectional operations with two operative deaths, one from respiratory insufficiency and the other from a bronchopleural fistula and massive hemorrhage. The rest of the patients had an uneventful recovery. The indications for resectional surgery are re-established for suitable cases. The underlying disease is the major determinant of the outcome of the surgery. Other modes of treatment are also discussed. Based on the analysis of these 18 cases, a guideline for the management of pulmonary monosporosis is proposed.

Aged

Surgical treatment of atypical pulmonary tuberculosis.

During a 12 year period from January 1962 to December 1973, 48 patients with atypical mycobacterial infection of the lung were treated surgically with excellent results. There were no deaths, and sputum conversion was achieved in all of them. The considerable drug resistance of the atypical mycobacteria and the possible ill effects of prolonged conservative treatment in cases with active disease and drug resistant organisms are pointed out. Early surgical treatment is recommended in such circumstances. Some bacterioligical and biological characteristics of atypical mycobacteria are also discussed.

Adult

[Evaluation of pipetting systems. II. Precision and accuracy of precision dispensers].

OBJECTIVE: To evaluate the precision and accuracy of the liquid dispensers being used in our institution. MATERIAL: A total of 15 dispensers (8 micro and 7 macro) of automatic, semiautomatic or manual types were evaluated. They had been in use from 0.5 to 7 years. METHODS: The volume dispensed was established by gravimetry using an analytical balance (Chio JP-160) and deionized distilled water as previously described. The microdispensers were evaluated using volumes of 20 and 100 microL, and the macrodispensers with 1 and 5 mL. Each dispenser was evaluated using 10 replicates: the mean and the CV (coefficient of variation) were calculated with the 10 replicates. The mean was transformed to per cent of the theoretical volume. Thus a 100% ratio of accuracy corresponds to a perfect accuracy. An important methodological aspect was that the 10 dispensing replicates were performed personally by the habitual user of the dispenser. RESULTS: The mean and CV are shown in table 2 for the microdispensers, and in table 3 for the macrodispenser. In the total 25 evaluation in tables 2 and 3 there were 8 instances in which precision was poor (CV above 3%) and also 8 cases of sizable inaccuracy (ratio outside of 100 +/- 5%). In 4 (2 micro and 2 macro) of these 8 inaccuracies, the error ranged from 10% to 22%. A minority was within the specifications of precision and accuracy claimed by the manufacturers of the dispensers with the exception of the manual microdispensers which were within specifications in most instances. We attribute the latter to the lack of a mechanical device in the manual dispensers. CONCLUSIONS: As in a previous evaluation of automatic micropipettes, we detected a high proportion of pipetting systems out of specifications in both precision and accuracy. The magnitude of error in the accuracy of 4 dispensers (10 to 22%) would be catastrophic in methods demanding good pipetting.

Calibration

[Patient data for evaluating reference values].

OBJECTIVE: To explore the use of data in patients as a way to evaluate the values of reference in clinical assays. Serum calcium (Ca) and phosphorus (P) were selected for this purpose. MATERIAL: A total of 836 consecutive admissions in a 10 week period were revised. Seventy percent (580 cases) had data of Ca and P in the first week following admission. A total of 424 were excluded by anyone of the following criteria: a) serum urea greater than 50 mg/dL, b) serum creatinine greater than 1.5 mg/dL; c) serum albumin less than 4 g/dL; d) lack of data of either urea, creatinine or albumin. These cutoff values were selected on the basis of a significant difference (t test) in the mean of Ca and/or P in patients grouped according to levels of the available data. The remainder of 156 cases is the selected population of study, and the 580 with Ca and P is the total population. METHODS: Ca and P were assayed in an analyzer (Coulter Chemistry) using the DAM and the Jaffé methods respectively. The precision during the period of study was adequate (CVs of 2.6% for Ca and 2.9% for P). RESULTS: Table 1 compares the mean, SD and CV of Ca and P in the selected versus the total population. There are significant reductions (F test) in the variability of Ca and P in the selected population (from a CV 9 to 5% in Ca and from 35 to 13% in P). Table 2 compares the age and sex distributions of the selected versus the total population. There are no significant differences (chi square test) although there is a lower proportion of people above 80 years of age in the selected population. The reference intervals of Ca and P in the selected population were obtained with the mean +/- 2 SD as both showed Gaussian distributions. These limits are compared in table 3 versus the values of the institution and of the manufacturer of the analyzer used. The P limits of this study fall intermediate to the other two, but in Ca they are the lowest of the three. Shortly after the completion of this study, the institutional values of Ca were changed to 8.5-10.5 mg/dL on the basis of the one year results in a WHO quality assessment scheme. The modification made the Ca limits of this study also intermediate to the other two series. The small differences in the limits have clinical and economic repercussions. Table 4 shows there is a 20% reduction in the number of abnormal tests (206 vs 259) and in the number of abnormal individuals (165 vs 203) using the limits of this study versus the institutional limits before modification. CONCLUSIONS: The data of Ca and P in a selected but representative population of patients proved to be a reliable way of evaluating its reference intervals. The reference intervals of this study were intermediate to those of the manufacturers of the analyzer and the laboratory (after modification). This finding suggests the strategy may be as good as more conventional approaches to establish reference values.

Adolescent