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Biomedical subjects

J A Saavedra

Publications and source records attributed to J A Saavedra.

At least 19 recordsLinked to original sources

A case of complete situs inversus.

Complete situs inversus is a rare syndrome, with overall frequency estimated at 1/10,000 births, resulting from abnormal rotation of the cardiac tube during embryogenesis, of unknown mechanism. Recent studies suggest that left-right asymmetry defects are likely to be due to genetic abnormalities in the lefty, nodal, i.v., HAND, ZIC3, Shh, ACVR2B and/or Pitxz genes. In dextrocardia with situs inversus the heart is structurally normal in 90-95% of cases, in contrast to dextroversion (dextrocardia with situs solitus), which has a high incidence of structural cardiac defects. Atrial septal defect is one of the most common congenital cardiac anomalies in adults. Diagnosis is based on clinical manifestations and simple complementary diagnostic exams like abdominal and thoracic radiography and electrocardiogram. Prognosis in isolated dextrocardia depends on the congenital cardiac defects present. By contrast, in dextrocardia with situs inversus life expectancy is similar to that of the general population. The authors present the case of a 64-year-old German man admitted to the emergency care unit with a diagnosis of embolic stroke due to atrial fibrillation with fast ventricular rate. As clinical history could not be assessed due to language limitations, routine admission tests were performed. They revealed complete situs inversus with corrected ostium secundum atrial septal defect. Finally, the anatomic, pathologic, embryologic and etiologic features of complete situs inversus and related abnormalities of the cardiac structures are presented. Special emphasis is given to genetic abnormalities, the study of which has seen great advances since the 1990s thanks to new techniques of DNA analysis.

Dextrocardia↗

Hyperfractionated chemoradiation with carbogen breathing, with or without erythropoietin: a stepwise developed treatment schedule for advanced head-and-neck cancer.

PURPOSE: To investigate the influence of carbogen breathing on chemoradiation and the effects of erythropoietin on transfusions. METHODS AND MATERIALS: From March 1996 to April 2000, 42 (4 Stage III and 38 Stage IV) patients with head and neck cancer were treated with a twice-a-day hyperfractionated schedule. Each fraction consisted of 5 mg/m(2) of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m(2) of carboplatin plus 8050 cGy in 7 weeks. Anemia was treated either by transfusion or by erythropoietin. RESULTS: Forty-one patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Five transfusions were given in the first group, but no transfusion was needed in the erythropoietin group. Local toxicities remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Forty-two complete responses were achieved. At two years actuarial local control, cause-specific survival and overall survival are respectively 85%, 69%, and 68%. At four years estimated probabilities of local control, cause-specific survival and overall survival are also 85%, 69%, and 68%. CONCLUSIONS: These results compare favorably with those of most reported studies. The addition of carbogen breathing appears to improve the results of chemoradiation alone. Erythropoietin therapy avoided transfusions.

Administration, Inhalation↗

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer.

BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

Adult↗

[Influence of the necessity of transfusion in anemia on the prognosis of ENT cancer in the protocol with concurrent hyperfractionation of carboplatin and irradiation].

Because of the determinant role of hemoglobin level in blood to the response of treatment (viewpoint admitted whether for irradiation or chemotherapic agents) the AA. have lead an analysis of a group of 36 patients suffering an advanced head and neck cancer (18 months mid-follow up and 30 months maximum) which underwent a program of concomitant radio-chemotherapy hyperfraccionated with carboplatin (the cytostatic) as part of each therapeutic fraction. The results in patients being transfused with an erytrocyte concentrate were compared with those from patients not having had any transfusion. The purpose of this study was the assessment of which are the influence on the prognostic of ENT-cancer resulting of the compulsory necessity of transfunding erytrocyte concentrates aroused by serious anemia presenting during the development of the schedule treatment. In brief, in that kind of patients needing transfusions of red blood cells concentrates because of serious anemia during the treatment (17% of the totality treated) were recorded 50% local failures, 33% metastases and only 17% of the totality were free of neoplasma at the end of the follow-up fixed. Instead between patients not having had transfusions (for treating anemia) the differences registered were 20% failures of loco-regional control and 13% metastases, whereas 67% were free of tumor at the end of the study. The conclusion drawn out is: the important influence on the prognostic of these tumors, when in the course of the scheduled treatment, appear severe anemia making the transfusions compulsory.

Aged↗

Tolerance of intravitreous interleukin-1 beta in the treatment of experimental vitreous hemorrhage.

We investigated the tolerance of human recombinant interleukin-1 beta (IL-1 beta) injected intravitreously and its putative role in the clearance of experimental vitreous hemorrhages. Three groups of 10 pigmented rabbits each were injected intravitreously with 0.1 ml autologous whole blood. Mean fundus revisualization times after blood clouding were as follows: group 1 (controls, blood injection only), 5.3 weeks; group 2 (100 units of IL-1 beta injected intravitreously 7 days after blood injection), 3.3 weeks; group 3 (1,000 units of IL-1 beta injected intravitreously 7 days after blood injection), 3.2 weeks. Group 4 (10 rabbits) was injected only with 1,000 units of IL-1 beta. Clinical examinations showed a transient mild inflammatory reaction in group 2 and a transient severe reaction in groups 3 and 4. Vitreous opacities, a whitish retinal reaction and vascular changes were seen in group 4. Electroretinography did not show a b-wave decrease in any group. These results suggest that low concentrations of IL-1 beta may be useful for nonsurgical treatment of human vitreous hemorrhage.

Animals↗

Insights into the role of thromboxane A2 and serotonin in the pathogenesis of unstable angina.

New research about platelet and endothelial functions is allowing us to better understand the pathogenesis of myocardial ischemic episodes in patients with unstable angina, creating new perspectives for the rational utilization of therapies. In patients with unstable angina, the episodes of symptomatic and silent ischemia are caused by repeated reductions of coronary blood flow. They are the result of the mechanical effect of the growing thrombus, which causes intermittent episodes of partial obstruction of the arterial lumen, in association with vasoconstriction at the stenotic site and dependent coronary arterial bed, produced by the cyclic release of platelet derived vasoactive products, namely thromboxane A2 and serotonin. Several studies, many of them in animal models of thrombosis, suggest that serotonin and thromboxane A2 are mediators of platelet aggregation, adynamic obstruction and coronary artery thrombosis. Because they cause coronary cyclic flow reductions, they are implicated in the pathogenesis of myocardial ischemic episodes during unstable angina. Drugs that interfere with the arachidonate pathway, and the 5-HT2-receptor antagonists, have been proven to decrease or abolish coronary cyclic flow variations in animal models and man. However, further studies should be done to test the hypothesis that the association of a 5-HT2-receptor antagonist with aspirin may contribute to decrease myocardial ischemia and prevent coronary occlusion in patients with unstable angina. Continuous Holter monitoring during the first week after admission in the hospital should be a good method to evaluate the eventual efficacy of this new class of drugs in abolishing or decreasing the frequency, intensity and duration of myocardial ischemic episodes in patients with unstable angina. The central role of serotonin in the pathogenesis of thrombotic events, and the presumed preventive effect of ketanserin, were the bases of a national multicenter pilot controlled study designed to evaluate the safety and efficacy of ketanserin plus aspirin in the secondary prevention of patients with unstable angina and non-Q wave myocardial infarction (KATUA Trial).

Angina, Unstable↗

Reduction of cardiovascular side effects associated with ocular administration of metipranolol by inclusion in polymeric nanocapsules.

A new formulation of metipranolol base for ophthalmic administration was developed consisting of a colloidal suspension of polyepsiloncaprolactone nanocapsules with an oily core (Migliol 840) in which the drug is dissolved. Physicochemical properties of the nanocapsules show that the polymer coating around the oily droplets causes an important reduction of the droplet size, with no significant modification of the surface charge noted. When this formulation was administered to rabbits, a reduction of intraocular pressure similar to that seen with commercial eye drops was observed. Nevertheless, the evaluation of the cardiovascular side effects clearly showed lower conjunctival absorption of the encapsulated drug compared with the commercial drops. The direct (bradycardia) and the indirect evaluation (based on the study of the influence on the hypotensive and positive chronotropic effects of isoprenaline) showed that blockage of beta-adrenoreceptors was reduced greatly by the topical administration of the new formulation.

Animals↗

Blockage of resting potassium conductance in frog muscle fibers by a toxin isolated from the sponge Haliclona viridis.

A fraction able to irreversibly depolarize sartorius muscle fibers was isolated from the marine sponge. The resting potential is decreased from -84 (-85, -83) mV (median and its 95% confidence interval) to -40 (-46, -30) mV. The fibers depolarized by the sponge toxin are restored to -54 (-57, -49) mV when external sodium is replaced by Tris or to -52 (-57, -47) mV when calcium is removed from the saline solution in the presence of 1 mM EDTA and 1 microM tetrodotoxin. Tetrodotoxin alone (1 micron) has no effect on the depolarization [-43 (-50, -37) mV] produced by the sponge and 5 mM manganese only repolarizes the fibers to -48 (-55, -40) mV. The depolarization is potentiated [-28 (-33, -23) mV] when chloride is replaced by glutamate in the external solution. The access resistance of the muscle fibers is not significantly changed from its control value of 2.74 (2.28, 3.30) M omega when toxin is added. By contrast 20 mM K+ superfused to the fibers changes membrane potential to -44 (-46, -42) mV and decreases access resistance to 1.99 (1.38, 2.87) M omega. The toxin is devoid of any effect on the endplate, since the depolarization of the postsynaptic membrane is identical to the extrajunctional area, and miniature endplate potentials of normal shape and high frequency are easy to record from toxin treated fibers. The action potential is not modified by the toxin. The toxin is a small polar compound insoluble in acetone and is likely to act on a receptor located on the outer phase of the membrane. The biological activity appears as a peak on elution with 1 M acetic acid on Bio Gel P2.

Animals↗

Effect of environment with low dinoflagellate concentration on the toxicity to mice of alcoholic extracts from the sponge Tedania ignis.

We have examined the toxicity of samples of sponges from mangrove lagoons in Venezuela, rich in dinoflagellates [1972 (1710, 4642) dinoflagellates/liter (median and 90% confidence interval of 4 samples, spanned over an 8 month period)]. After transferring them for 135 days to a coral reef poor in dinoflagellates [35 (18, 87) dinoflagellates/liter (4 samples)] there was an 85% decrease in lethal potency to mice.

Animals↗

Ichthyotoxism by a paralytic toxin produced by marine dinoflagellates of the genus Ceratium: relationship to fraction beta isolated from the sponge Tedania ignis.

Two hundred tons of the plankton feeding sardine Cetengraulis edentulus died in March 1982, in Carenero (10 degrees 10' N, 66 degrees 05' W), Venezuela. A fraction was extracted from this fish that was toxic to mice by i.p. injection. The animals died in less than 4 min and showed generalized flaccid paralysis. Gel filtration on Sephadex G15 and Bio Gel P2 showed that the toxicity is related to a fraction that blocks the release of acetylcholine in frog (Rana pipiens) neuromuscular junctions. This toxin is similar in chemical properties and presynaptic effect to fraction beta isolated from the sponge T. ignis by Sevcik and Barboza. Fractions of the same biological action and chemical properties were isolated from plankton samples collected in the area of the ichthyotoxism. The correlation analysis between the presence of toxin and a plankton species in a sample, was carried out with a feasibility index (as %) defined by Sevcik and Mijares. Random samples of plankton (29) were collected in 3 locations (11 degrees 50' N, 68 degrees 15' W; 10 degrees 36' 24'' N, 67 degrees 14'7'' W and 10 degrees 21' N, 64 degrees 21' W). The correlation carried out over 167 species of phytoplankton present in the samples indicates that the species most likely to be responsible for the production of the fraction beta, in order of feasibility index (in parentheses) are: Ceratium furca (54%), Protoperidinium sp. (1.7%) and Protoperidinium pallidum (1.6%). In some samples a fraction similar to fraction alpha from T. ignis was also found. The identification of the phytoplankton responsible for this fraction is, however, less conclusive. The feasibility indexes are: Protoperidinium sp. (58%), Ceratium inflatum (30%), Podolampas sp. (23%), Ornithocercus steini (21%). The genus Ceratium was the second most abundant in Carenero at the time of the fish death. These results suggest that the toxins isolated from C. edentulus and T. ignis have a planktonic origin.

Animals↗

[Male XX-syndrome].

Described in this paper is a patient, aged eleven years and eight months, with micropenis, dorsal prepuce, and rugous, partially bifid scrotum. FSH and LH values below normal were obtained from hormonal investigation. LH-RH stimulation was followed by retarded FSH response of moderate intensity, while the LH profile was moderately strong. Cytogenetic tests revealed the presence of 25 per cent of female sex chromatin. The karyotype was 46 XX. The patient did not have internal female genital organs, and his gonads were of testicular appearance. Histologically, both testicles exhibited tubules with primitive germinal cells and Sertoli cells. An inconspicuous number of Leydig cells was recorded from the interstitium.

Child↗

[Experimental contribution on the biochemical and morphological study of lung maturation in Wistar rats].

This is a research on the pulmonary normal maturity of a Wistar's Rat from the biochemic and morphological point of view. To do that we have chosen 3 lots of 5 rats each. The animals were sacrificed by killing them up to 15, 18 and 21 days of pregnancy. Then we have removed the amniotic liquid of each rat to know or study the creatinin concentration and the lecithin/sphingomyelin relation or report. To every foetus that we have got from every rat we have removed or extirpated the lungs to do a study under the optic microscope by using the hematoxilin-eosin together with the Fontana-Masson techniques.

Amniotic Fluid↗

[Experimental contribution on the biochemical study of normal and pathologic (diabetes) lung maturation in the Wister rat].

This is a research on the pulmonary normal and pathological (Diabetes) maturity of the WISTAR's Rat. To do that we have chosen 6 lots of rats. The animals were sacrificed by killing them up to 15., 18. and 21. days of pregnancy, then we removed the amniotic liquid from each rat to know or find out the lecithin/sphingomyelin and creatinin relations or reports.

Amniotic Fluid↗

[Experimental contribution on the morphological study of normal and pathologic (diabetic) lung maturity in the Wistar rat. Comparison with the biochemical study].

This is a research on the pulmonary normal and pathological (Diabetes) of a Wistar's rat from a morphological point of view doing a comparative study with biochimic data or results. To do this we have sacrified by killing the different animals up to 15, 18 and 21 days of pregnancy and then we have removed or extripated the foetus lungs to do a study under the optic microscope by using the Hematoxilin-eosin together with the Fontana-Masson-techniques.

Animals↗

[Echographic study in early pregnancy. I. Parameter of the uterus].

The echographic pattern of the growing uterus in normal pregnant women and threatened abortion with analysis of longitudinal, antero-posterior and transverse, the area and volume of the uterus has been studied. There is a significant difference between both groups.

Abortion, Threatened↗

[Echographic study in early pregnancy. II. Amnion cavity parameter].

Ultrasonic B-scanning was used to study 201 patients in early pregnancy. We divided the material in two groups with clinical signs of threatened and a third group of normal pregnancy. The growth of three mean diameters of gestational sac is analyzed. An assesment of gestational sac area and volume is included. The data are represented in terms of regression lines.

Abortion, Threatened↗