Pentamidine-induced torsade de pointes.
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Biomedical subjects
Publications and source records attributed to A Gonzalez.
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Twenty-three patients with angina who were undergoing diagnostic cardiac catheterization underwent cardiac pacing with simultaneous hemodynamic and Doppler echocardiographic evaluation to assess the effects of pacing-induced ischemic on mitral valve velocity. Seventeen patients had significant coronary artery disease, and six patients had normal coronary arteries. Doppler and hemodynamic measurements were performed at rest and immediately after pacing was discontinued to 91% +/- 7% of maximal predicted heart rate. Seven patients experienced new or significant increases in severity of mitral regurgitation after pacing as revealed by Doppler examination. This group had a significant increase (p = 0.007) in early but not in late peak filling velocities immediately after pacing was discontinued, with a resultant decrease in late to early ratios, which decreased from 1.01% +/- 0.12 to 0.70% +/- 0.19 (p = 0.006). Left ventricular end-diastolic pressure increased significantly from 16.7% +/- 6.8 mm Hg to 29.4% +/- 5.3 mm Hg after cardiac pacing (p less than 0.001). Patients with coronary disease who did not develop mitral regurgitation also had significant increases in left ventricular end-diastolic pressure from 18.7% +/- 5.8 mm Hg to 24.3% +/- 8.6 mm Hg (p less than 0.05). There were no changes in late or early wave amplitude, late to early ratio, or other Doppler measurements in any of the other groups. We conclude that mitral regurgitation caused by pacing-induced myocardial ischemia normalizes Doppler indices of mitral inflow, which in turn, may mask persistent or worsened left ventricular diastolic dysfunction.
Abdominal distention during pneumoperitoneum results in a marked increase in plasma arginine vasopressin levels, which has been ascribed to an increase in intrathoracic pressure. Because of this relationship, tense ascites could contribute to nonosmotic release of antidiuretic hormone, to the development of hyponatremia, and eventually to further ascites formation. The effect of pneumoperitoneum, thoracocentesis, and paracentesis on plasma arginine vasopressin levels was studied in three groups of patients, and the mechanism by which these maneuvers may induce these changes was investigated. Patients with pleural effusion, pneumothorax, or ascites showed a significant increase in plasma arginine vasopressin levels, and thoracocentesis or paracentesis resulted in a decrease in these levels. Plasma vasopressin levels increased significantly during pneumoperitoneum, as did intrathoracic and atrial pressures; the atrial transmural pressure gradient declined. However, no changes in plasma levels of norepinephrine, aldosterone, and renin activity were observed during pneumoperitoneum. Changes in plasma arginine vasopressin levels correlated with the changes in intrathoracic and atrial pressures and transmural pressure gradient. The authors conclude that increased intrathoracic pressure is associated with an increase in plasma arginine vasopressin levels and propose that ascites could be a factor promoting vasopressin release by acting on intrathoracic volume receptors in decompensated cirrhotics.
Synthetic peptides modelled according to the amino acid sequences derived from the repeated domains of five Trypanosoma cruzi antigens were used in an immunoradiometric assay to detect antibodies appearing after natural human infections. An enzyme-linked immunosorbent assay and an indirect immunofluorescence assay performed with a complex antigenic mixture from parasites were used as controls. The results indicate that the synthetic peptides were recognized by a large proportion of serum samples collected from 34 patients with Chagas' disease in Chile and point to their possible use in diagnosis.
The authors used a randomized, placebo-controlled design to assess the therapeutic efficacy of adjunctive imipramine, added to fluphenazine decanoate and benztropine, among well-stabilized, negative-symptom schizophrenia and schizoaffective disorder patients who additionally met operationalized criteria for postpsychotic depression. The outcome of the imipramine-treated group was superior in both global ratings and a specific negative-symptom scale. Exacerbation of psychotic symptomatology was not found to be problematic. The implications of this study are discussed in terms of a potential strategy for pharmacotherapy among certain negative-symptom patients and in terms of its relevance to a possible pathophysiological basis for the negative-symptom state.
Syrian hamsters were treated with ethinylestradiol and maintained on a diet containing alpha-naphthoflavone (alpha NF), a regimen that produces a high incidence of liver tumors. Morphologic analyses (light microscopy, immunoperoxidase studies, and electron microscopy) were performed on livers of these animals. After 4 months of hormone plus alpha NF treatment, marked hepatocyte cell changes were already present, as demonstrated by loss of eosinophilic staining of hepatocyte cytoplasm. Large multinucleated hepatocytes exhibiting frequent mitoses were observed around central veins. After 5 months of treatment, there was proliferation of bile ducts, and small cells with eosinophilic cytoplasm resembling hepatocytes appeared surrounding these bile ducts. At 7 to 8 months, the first tumor nodules (foci) were seen. Tumor foci in the portal area consisted of small clusters of large cells resembling hepatocytes with irregular nuclei. At the same time, dysplastic glands were identified among proliferating bile ducts. By 8 to 10 months, large tumors were present. These were trabecular hepatocellular carcinomas with widely varying individual cell morphology. Compared with adjacent liver, dysplastic glands in the portal areas, microcarcinomas, and large tumors all showed intense immunostaining for cytokeratin. Rats treated with the same regimen also developed hepatic tumors, but the light and electron microscopy results and immunohistochemical profiles were very different. Altered hepatic foci composed of small hepatocytes were typically prominent; however, malignant tumors did not arise from the portal area. Neither altered foci nor tumors stained significantly for cytokeratin. These data suggest that the biochemical events giving rise to these liver tumors differ between the species studied, despite the animals being exposed to the same treatment regimens.
The brains of the chicken, Gallus domesticus, and two amphibians, the anuran Rana ridibunda and the urodele Pleurodeles waltlii, were investigated by means of immunohistochemical techniques with antibodies against dopamine (DA) and tyrosine hydroxylase (TH). As could be expected on the basis of the catecholamine biosynthetic pathway, cell bodies that are immunopositive for the DA antiserum also stain with the TH antibodies. However, a remarkable discrepancy is observed in the hypothalamic periventricular organ where liquor contacting cells exhibit DA- but no TH-immunoreactivity. Since similar results have been obtained in reptiles but not in mammals, it may be concluded that these putative DA-accumulating cells are a primitive brain character of non-mammalian vertebrates.
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The optimum superovulatory dose of Folltropin was determined and compared with a standard 28 mg dose of FSH-P in beef heifers. In Experiment 1, mean numbers of corpora lutea (CL) did not differ among the groups treated with 10, 20, 30 or 40 mg Folltropin or FSH-P, and the mean CL number was reduced (P<0.05) only in the 5 mg Folltropin group. Mean numbers of ova/embryos recovered, fertilized and transferable were greater (P<0.05) for the 10, 20 and 30 mg Folltropin groups than for the 5 mg group. The 40 mg Folltropin group and the FSH-P group were intermediate. The percentage of fertilized and transferable embryos did not differ over the dosages used in this experiment. In Experiment 2, mean numbers of CL were greater for the 9, 18 and 36 mg Folltropin groups than for the 4.5 mg group, with the 9 mg group being lower than the 36 mg group (P<0.05). The 18 mg group was intermediate and did not differ. Mean numbers of ova/embryos recovered and fertilized ova were greater for the 9, 18 and 36 mg groups (P<0.05) than for the 4.5 mg group. The percent of fertilized and mean number and percentage of transferable embryos did not differ among treatments. We conclude that Folltropin may be a satisfactory superovulatory replacement for FSH-P and that a dose of 18 to 20 mg Folltropin may be within the optimum superovulatory dosage range for beef heifers. Dosages of Folltropin of more than twice the optimum did not result in deterioration of ova/embryo quality.
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The afferent connections of the striatum and the nucleus accumbens of the lizard Gekko gecko were studied with retrograde tracing by means of horseradish peroxidase and Fluoro-Gold and with anterograde tracing by means of Phaseolus vulgaris leukoagglutinin. The striatum receives projections from the cortex, the dorsal ventricular ridge, the lateral amygdaloid nucleus, the globus pallidus, the anterior peduncular nucleus, the ventral tegmental area and substantia nigra, the area ventral to the substantia nigra, and the dorsal thalamus. The nucleus accumbens is projected upon by the cortex, the diagonal band, the ventral pallidum, the lateral preoptic area, the ventral tegmental area, and the dorsal thalamus. The source of the cortical projection to the striatum and the nucleus accumbens is a longitudinal zone in the dorsal cortex that, rostrally in the hemisphere, is located medially and, more caudally, in its middle one third. The medial and rostrolateral areas of the dorsal ventricular ridge each project to the striatum in a vertical zone. The fibers from the caudolateral area of the ridge end in two oblique bands located parallel to the border between the dorsal ventricular ridge and the striatum. The pathways from the mesencephalic tegmentum to the striatum and the nucleus accumbens show a medial to lateral topography. This is similar to the situation in birds, but contrary to that in mammals in which these pathways are extensively interconnected. The specific sensory nuclei of the dorsal thalamus were found to project not only to the dorsal ventricular ridge, but also, and in a topographical fashion, to the striatum. The dorsomedial thalamic nucleus, which innervates the dorsal ventricular ridge, has additional projections to the striatum and the nucleus accumbens. This projection pattern is similar to that of the intralaminar thalamic nuclei of birds and mammals.
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The trigeminal mesencephalic nucleus (Mes V) of the frog Rana ridibunda, has been studied by means of electron microscopic techniques. Mes V neurons are large (20-30 microns in diameter). They are dispersed in the optic tectum and show round to oval cell bodies. Both multipolar and unipolar cells were observed. Their cytoplasm is very rich in organelles with well-developed rough endoplasmic reticulum that forms prominent and scattered Nissl bodies. Numerous small mitochondria, Golgi dyctiosomes, neurotubules and neurofilaments are distributed among the granular endoplasmic reticulum. A striking feature is the existence of abundant lysosome-like particles throughout the cytoplasm. In the surface of Mes V neurons spinous processes are absent and synaptic contacts on the perikarya are scarce. Two types of synapses, one with spherical translucent vesicles and the other with elongated translucent vesicles, contact on either the cell body or the dendrites of Mes V cells.
Chronic natural or synthetic estrogen treatment of Syrian golden hamsters leads to the development of malignant renal neoplasms. In the present study, morphological and immunohistochemical studies were performed to further characterize the estrogen-induced hamster renal tumors. The neoplasms were composed of two distinct cell populations: a large-cell component that appeared highly epithelial, and a poorly differentiated small-cell component. Importantly, both cell types had epithelial characteristics, since they contained desmosomes at their cell surfaces. However, the large-cell component possessed additional epithelial features such as microvilli, intracytoplasmic lumens, and cilia. Comparative studies of renal tumors and developing renal tissue from fetal and newborn hamsters revealed remarkable histological similarities. Morphologically, the large tumor cells resembled early metanephric tubules and the small tumor cells were very similar to the blastemal cells of the developing kidney. The earliest tumor foci were found after 4.5 months of treatment. They were consistently found in the kidney interstitium in proximity to large arteries. Immunohistochemical staining for intermediate filaments in developing fetal and newborn kidneys demonstrated cytokeratin in renal tubules, desmin in blastemal cells, and vimentin in stromal cells. Estrogen-induced renal tumor cells uniquely possessed reactivity for all three intermediate filaments, clearly demonstrating their epithelial and mesenchymal characteristics. Based on their morphological resemblance to developing embryonic kidney cells and the presence of both epithelial and mesenchymal intermediate filaments, our findings provide strong evidence that the cell of origin of this malignant tumor is a precursor cell that is committed to an epithelial differentiation pathway.
Despite improved prenatal care, infants of diabetic mothers (IDM) have an increased risk of congenital malformations. We report on an IDM with multiple congenital anomalies consistent with the polyasplenia complex with associated mesocardia and renal agenesis. The morphologic characteristics of these malformations are discussed. Special emphasis is given to the polyasplenia complex as an example of midline developmental field defect. The importance of maternal levels of hemoglobin A1c in relation to congenital malformations is addressed.
The proto-oncogene c-myc, whose gene product has a role in replication, is overexpressed in the human promyelocytic leukemia HL-60 cell line. Treatment of HL-60 cells with an antisense oligodeoxyribonucleotide complementary to the start codon and the next four codons of c-myc mRNA has previously been observed to inhibit c-myc protein expression and cell proliferation in a sequence-specific, dose-dependent manner. Comparable effects are seen upon treatment of HL-60 cells with dimethylsulfoxide (Me2SO), which is also known to induce granulocytic differentiation of HL-60 cells. Hence, the effects of antisense oligomers on cellular differentiation were examined and compared with Me2SO. Differentiation of HL-60 cells into forms with granulocytic characteristics was found to be enhanced in a sequence-specific manner by the anti-c-myc oligomer. No synergism was observed between the anti-c-myc oligomer and Me2SO in stimulating cellular differentiation. In contrast, synergism did appear in the inhibition of cell proliferation. Finally, the anti-c-myc oligomer uniformly inhibited colony formation in semisolid medium. It is possible that further reduction in the level of c-myc expression by antisense oligomer inhibition may be sufficient to allow terminal granulocytic differentiation and reverse transformation.
Two gonadotropin-releasing hormone (GnRH) peptides with a cystein substitution of the first (C1-GnRH) or tenth (C10-GnRH) amino acid were conjugated to ovalbumin and equine serum albumin, respectively, via the sulfhydryl group of the introduced cysteine. Animals were immunized three times at 3-wk intervals with both conjugates in either saline (n = 5), Freund's complete adjuvant (FCA; n = 5), Havlogen (n = 6), Ribi adjuvant system (RAS; n = 5), dimethyl dioctadecyl ammonium bromide (DDA; n = 4), Alhydrogel (n = 5) or Regressin (n = 5). Animals immunized with conjugates in saline or RAS did not produce anti-GnRH titers. The highest anti-GnRH titers were produced by animals treated with FCA. The Alhydrogel and DDA treatments stimulated the production of GnRH antibodies in all animals treated, but titers were lower than in animals immunized with FCA. When vaccines were formulated with Havlogen or Regressin, anti-GnRH titers were low or absent. Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels were depressed in FCA and in Alhydrogel treated animals. The antisera raised were predominantly directed against either the carboxy- or the amino-terminal end of the GnRH peptide, or directed equally against both, depending on the individual animal. Results suggest that no epitope of GnRH dominates the immune response in cattle and show that the best alternative to FCA is Alhydrogel.