Biomedical subjects
Publications and source records attributed to L Rodriguez.
We report a 2-years-old infant who presented psychomotor delay and facial dysmorphic features. He has a partial monosomy of 15q resulting from de novo t(15;22)(q15;p11). Up to now three other cases with a similar 15q monosomy have been reported, but the present case is the first one with a "pure" monosomy 15q.
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Seropositivity to the AIDS-associated retrovirus, HTLV-III/LAV, has profound implications. Simple and reliable tests are needed to detect such antibodies. A rapid, sensitive indirect immunofluorescence assay (IFA) on acetone-fixed virus-producing CEM/LAV-N1 cells was adapted for detection of human antibodies to HTLV-III/LAV. Specific and nonspecific patterns of of immunofluorescent reactivity were easily distinguished, and results paralleled those obtained by Western blotting and radioimmunoprecipitation (RIP), indicating that there is no need to confirm IFA positivity. In contrast, the commercial enzyme-linked immunosorbent assay (ELISA) was less reliable. False positives occurred with sera from seven hemophiliacs that were negative on Western blots, and false-negative reactions were observed on two occasions. These involved low-titer AIDS-patients' sera that were positive on Western blots, and from one of which virus was successfully isolated. Our results emphasize the requirement for confirmatory assays when the ELISA test is used for primary screening of sera for antibodies to HTLV-III/LAV. The IFA method is especially well-suited to quantitative analysis of serum antibody levels. Our data suggest that serum antibody titers rise as disease progression occurs, ultimately falling as severe complications ensue. It is suggested that in laboratories where the demand for HTLV-III/LAV antibody testing is not excessive (1,000-2,000 sera/month), IFA could serve as the only serological assay for both screening and epidemiological purposes.
In Cuba and in the German Democratic Republic (GDR) a total of 24,412 pregnant women were tested for maternal serum alpha-fetoprotein (MSAFP) at the 16th to 20th week of gestation. An inexpensive and partly automated ultramicroliter enzyme immunoassay (ELISA) with final volumes of 10 microliter was used to analyze simultaneously 50 samples. The intraassay coefficient of variation (CV) of 5-8% and day/day CVs of 6-10.5% were obtained with a test frequency of 320 assays/day. A cut-off level of twice the median value (MoM) was chosen. An amniocentesis was done in a total of 0.5% (in the GDR) and 0.7% (in Cuba) of the screened women. The prevalence of open neural tube defects (ONTD) was calculated from the present study and was 1.43% in Cuba and 1.34% in the GDR. Through MSAFP screening 88.2% ONTD were detected. There was no therapeutic abortion of a normal fetus. The approximate cost for this program was about 2.36 marks-GDR per patient screened, or about 2,048 marks per ONTD detected.
Saccharomyces cerevisiae alpha factor pheromone arrest growth of cells of the a mating type (MAT a) at the G1 phase of the cell cycle. When treatment of MAT a cells with alpha factor was carried out in the presence of anticalmodulin drugs, trifluoperazine or chlorpromazine, the extent of cell growth arrest induced by alpha factor was reduced or even became undetectable. These results lend support to the hypothesis that calmodulin plays a role as mediator in the action of alpha factor on MAT a cells.
Serum samples from 850 individuals from Venezuela were tested for the presence of antibodies to HTLV-III/LAV virus, the probable etiological agent of acquired immune deficiency syndrome (AIDS). At the time of the study, none of the individuals tested had symptoms indicative of AIDS or related disorders. Viral antibodies were assayed by indirect immunofluorescence (IF) assay, using a chronically infected, HTLV-III/LAV producer cell line CEM/LAV-NIT established in our laboratory. Twenty individuals (2.5%), 8 of them (40%) female, were seropositive by IF and by confirmatory Western blotting and radioimmunoprecipitation assays. The seropositivity rate ranged from 2.4% (11 of 465) in the general healthy population, 4% (2 of 50) among patients with Chagas' disease, and up to 29.2% (7 of 24) among patients with acute malaria infection. The titers of HTLV-III/LAV antibodies ranged from 1:40 to 1:640. In addition, 2 of 36 patients with hemophilia A (5.5%) also had antibodies to HTLV-III/LAV. Two of 7 patients with acute malaria had specific antibodies both to HTLV-III/LAV and HTLV-I, as determined by IF and Western blotting. None of over 169 randomly chosen, healthy blood donors from seven major Venezuelan cities, as well as none of 99 patients with leukemia/lymphoma, had antibodies to HTLV-III/LAV. The presence of specific antibodies among various Venezuelan populations indicates that HTLV-III/LAV, or a closely related cross-reactive virus, is indigenous in Latin American subjects as was previously indicated for tropical populations of central Africa. Isolation and characterization of this virus will help to understand the origin and etiology of AIDS.
It has been shown in different groups of patients with variant angina that coronary spasm can be reproduced by physiologic maneuvers and pharmacologic agents. It is not known, however, to what extent different stimuli can induce spasm in the same patient. To investigate whether coronary arterial spasm results from specific abnormal agonist-receptor interactions or from a local nonspecific coronary supersensitivity to different stimuli, 28 patients with vasospastic angina were submitted to a series of diverse vasoconstrictive stimuli known to provoke coronary spasm. Ergonovine, hyperventilation, handgrip, cold pressor, and exercise-tests, were carried out in all 28 patients. In the last 15 patients histamine was also administered. Spasm was provoked by ergonovine in 96% of patients, by hyperventilation in 54%, by histamine in 47%, by exercise in 46%, and by the cold pressor and handgrip tests in 11% and 7%, respectively. No significant differences were found in the responses to provocative tests of patients with normal coronary arteries or nonsignificant stenoses and those with significant lesions. In the same individual, spasm was induced by at least two vasoconstrictive stimuli, although with a different mechanism of action, in 82% of patients and spasm was induced by three or more stimuli in 39%. Tests were repeated in at least 23 patients and short-term reproducibility paralleled sensitivity. These results suggest that in patients with variant angina, a local nonspecific supersensitivity rather than an abnormal specific agonist-receptor interaction plays a major role in the genesis of coronary arterial spasm.
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Fourteen patients with various forms of psoriasis participated in a clinical study to characterize the pharmacokinetics of etretinate before, during, and after 6 months of therapy. A single 100 mg dose was initially given, followed 2 days later by approximately 170 days of multiple dosing with 25 mg one, two, three, or four times a day depending on the subject's response and tolerance. Blood samples were drawn for 48 hours after the initial dose, for 12 hours after dosing at monthly intervals, and for up to 8 months after administration of the last dose. Blood concentrations of etretinate were determined by a specific reverse-phase gradient elution HPLC assay. Blood concentrations after the first dose declined with an apparent t1/2 of approximately 7 hours, whereas those after the last dose declined with an apparent t1/2 of approximately 120 days. The lengthening of the t1/2 during chronic dosing appears to result from the cumulation of blood concentrations in the measurable range rather than from time-related alterations in drug kinetics. This is substantiated by the fact that etretinate blood concentration--time data for the entire course of therapy were fit by a nonlinear least-squares computer program designed to accommodate changes in the dosing regimen. A single polyexponential kinetic equation described the entire 6-month course of therapy as well as the 8-month washout without the need to invoke nonlinear kinetics. Although single-dose kinetic data for etretinate may not be good predictors of steady-state blood concentrations, etretinate appears to follow linear kinetics during these dosing regimens.
We studied the influence of the following variables on the time interval from initiation of an intravenous infusion of 750,000 U of streptokinase until reperfusion (reperfusion time) in 140 consecutive patients with an evolving acute myocardial infarction: (1) the rate of infusion of streptokinase, (2) the duration of chest pain before initiation of treatment, (3) patient age, (4) patient sex, (5) location of infarction, (6) history of previous myocardial infarction, and (7) pretreatment pathologic Q waves. The time of reperfusion was recognized by clinical criteria that were completely concordant with the anatomic findings in all 119 patients in whom patency or occlusion of the artery of infarction was established at delayed angiography (n = 116) or at postmortem examination (n = 3). The mean reperfusion time for the 129 patients for whom data were available was 49 +/- 36 min. The reperfusion time was inversely related to the rate of infusion of streptokinase (r = .41, p less than .001), but this effect of infusion rate appeared to plateau at rates of greater than 500 U/kg/min. In the 64 patients receiving infusions at rates of 500 U/kg/min or less, the mean reperfusion time was 60 +/- 40 min, whereas in the 58 patients receiving the drug at rates greater than 500 U/kg/min it was 35 +/- 22 min (p less than .001). The duration of chest pain before treatment was the only other studied variable found to influence the reperfusion time, but only at infusion rates of less than 250 U/kg/min (r = .6, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
This report compares the results of intracoronary (IC) and intravenous (IV) streptokinase in a sequential series of 200 patients (IC = 81 and IV = 119) admitted within 3 hours of the onset of an acute myocardial infarction. Reperfusion was achieved in 71 of 81 (88%) patients in the IC group and in 113 of 119 (95%) patients in the IV group (p = NS) 35 +/- 27 and 42 +/- 33 minutes after commencement of treatment respectively (p = NS). The interval from onset of symptoms to reperfusion was significantly longer in the IC than in the IV group, 235 +/- 62 versus 175 +/- 61 minutes (p less than 0.001). Mean values of peak creatine kinase-MB were 152 +/- 117 IU/L in the IC group and 117 +/- 79 IU/L in the IV group (p less than 0.05). Three patients in the IC group and 16 patients in the IV group suffered major hemorrhagic complications. In-hospital mortality was 7 of 81 (8.7%) in the IC group and 10 of 119 (8.4%) in the IV group (p = NS). We conclude that IV administration of streptokinase in patients with an acute myocardial infarction is at least as efficacious as IC administration.
Bleeding during open-heart surgery is a not unusual complication. Rupture of the inferior vena cava during dissection of the heart from adhesions from a previous operation for mitral disease or congenital palliative surgery is a serious and sometimes fatal complication. Its treatment is a challenge even to the most experienced heart surgeon. In two of our three patients, vena cava rupture occurred during open-heart surgery for correction of mitral and aortic valvular disease. In one patient, congenital infundibular stricture of the right ventricle, associated with tricuspid valve insufficiency, was present. In this report, some relevant data were presented from each case and the aetiology of the rupture is discussed.
A 63-year-old man was operated upon with replacement of the aortic valve, mitral valve and ascending aorta with re-implantation of the coronary arteries. A composite graft with a 27 mm Björk-Shiley tilting disc prosthesis was inserted with 3 continuous Prolene sutures in the aortic position. The coronary arteries were thereafter re-implanted in holes made in the graft. A 31 mm Björk-Shiley valve was sutured in the mitral position with about 20 isolated mattress sutures of Ti-Cron. Selective myocardial hypothermia was instituted with Ringer's solution of 4 degrees C. The total perfusion time was 185 min compared with 240 and 275 min in two previously reported, similar cases. We consider that the use of cardioplegia, a composite graft and continuous sutures makes it possible to reduce the operation time in these complex cases. Our patient is in good condition 9 months postoperatively.
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