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Biomedical subjects

N Nguyen

Publications and source records attributed to N Nguyen.

At least 19 recordsLinked to original sources

Comparison of technetium-99m sestamibi and thallium-201 retention characteristics in canine myocardium.

OBJECTIVES: The aim of this study was to compare the myocardial retention of technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood flow at different time points after tracer injection. BACKGROUND: Technetium-99m sestamibi has been proposed as a new perfusion tracer with better physical characteristics than those of thallium-201 for scintigraphic imaging. However, no studies have simultaneously compared the ability of both tracers to assess myocardial blood flow during pharmacologic vasodilation. METHODS: The myocardial retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of blood flow induced by regional coronary occlusion and dipyridamole infusion in an open chest dog model. Myocardial retention of both tracers was determined by in vitro tissue counting at 2, 5, and 20 min after tracer injection and was correlated with microsphere-determined blood flow. RESULTS: Thallium-201 demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2 min after tracer injection, there was an almost linear relation between the retention of both tracers and myocardial blood flow over a wide flow range. However, this relation was not maintained over time. At 20 min after injection, the retention of both tracers underestimated myocardial blood flow at higher flow rates. At 2, 5 and 20 min after injection, increments of relative tracer retention between the different levels of flow were always greater for thallium-201 than for Tc-99m sestamibi. CONCLUSIONS: Thallium-201 displays more suitable physiologic characteristics as a flow tracer and may allow better differentiation of myocardial regions with different levels of coronary flow reserve. For both tracers, early cardiac imaging may minimize underestimation of blood flow at higher flow rates.

Animals

The relationship between myocardial retention of technetium-99m teboroxime and myocardial blood flow.

OBJECTIVES: The aim of this study was to define the temporal changes in the relationship between technetium-99m teboroxime tissue retention and myocardial blood flow in a canine model. BACKGROUND: Technetium-99m teboroxime is a new neutral lipophilic myocardial perfusion agent. It is known to be highly extracted by the myocardium but to have a rapid clearance rate. METHODS: A wide range of myocardial blood flow was induced in each experiment by regional coronary occlusion and dipyridamole infusion. Myocardial retention of technetium-99m teboroxime was determined by in vitro tissue counting at 1, 2 or 5 min after injection of the tracer. Tracer retention was correlated with microsphere-determined blood flow and the data were fitted to nonlinear functions. RESULTS: Correlation coefficients for these functions were 0.92, 0.95 and 0.95 at 1, 2, and 5 min, respectively. At 1 min after injection, the relationship of technetium-99m teboroxime retention to blood flow was linear over a wide flow range, becoming nonlinear at flow rates greater than 4.5 ml/min per g. After 5 min the retention-flow relationship was linear only to 2.5 ml/min per g, above which little change in retention was noted. Normalized myocardial retention, expressed as a percent of the retention at 1 ml/min per g, was also calculated. At flow rates of 1, 2, 3, 4 and 5 ml/min per g, normalized retention was 100, 169, 228, 277 and 317% at 1 min and 100, 171, 217, 239 and 237% at 5 min after injection. CONCLUSIONS: At 1 min after injection, the relationship of technetium-99m teboroxime myocardial retention to blood flow is well maintained over a wide range of flow. However, after only 5 min, tracer retention underestimates flow changes at moderate and high flow rates. Thus, rapid acquisition protocols are necessary to fully exploit the potential of this promising new tracer in the evaluation of myocardial perfusion.

Animals

Growth cone guidance by floor plate cells in the spinal cord of zebrafish embryos.

The spinal cord of early zebrafish embryos contains a small number of neuronal classes whose growth cones all follow stereotyped, cell-specific pathways to their targets. Two classes of spinal neurons make cell-specific turns at or near the ventral midline of the spinal cord, which is occupied by a single row of midline floor plate cells. We tested whether these cells guide the growth cones by examining embryos missing the midline floor plate cells due either to laser ablation of the cells or to a mutation (cyc-1). In these embryos the growth cones followed both normal and aberrant pathways once near the ventral midline. This suggests that normally the midline floor plate cells do provide guidance cues, but that these cues are not obligatory.

Animals

Hypotony and corneal edema secondary to patching in normal eyes.

Over the past decade investigators have used patching when studying corneal response to eye lid closure. In these studies, corneal edema was thought to be secondary to hypoxia, and the results were used to predict corneal response to contact lens wear. None of these studies have measured or controlled the intraocular pressure (IOP) during eye patching. Reports in the literature indicate that hypotonous and hypertensive events may induce corneal edema. In order to evaluate the IOP and corresponding corneal changes, measurements were made on subjects with patched eyes. Thirty subjects were unilaterally patched and randomized into tight and light patch groups to maintain complete lid closure for 4 h. Measurements of IOP and corneal thickness (CT) were made at baseline and at hourly intervals. The contralateral eye served as the control for each subject. Our results indicate a significant decrease in IOP and a corresponding increase in CT in the tight patched group as compared to the light patch group, and baseline controls. These results suggest that the corneal edema which results from patching of the eye may be due to hypotony, or a combination of factors affecting corneal function, rather than hypoxia.

Bandages

[A multiparameter method of computer-assisted objective vocal evaluation].

The aim of this study is to validate an aid for the evaluation of dysphonia with objective measurements. We recorded exhaled airflow, fundamental frequency and sound level pressure, for a sustained vowel "a", with 51 dysphonic subjects and 15 normal subjects. The following measurements are made on these three parameters: mean value, standard deviation and coefficient of variation. The exhaled airflow volume was also computed for a duration of 2 seconds. A principal components analysis of the measurements indicated that it is possible to recognise the classes of vocal evaluation and vocal pathology. These findings reinforce on objective aid for the vocal evaluation of dysphonia.

Diagnosis, Computer-Assisted

Effect of hypoimmunoglobulinemia on laboratory evaluation of multiple sclerosis.

A female patient with Crohn's disease was assessed by laboratory evaluation for multiple sclerosis. Because of her hypoproteinemia, she was given an albumin infusion, which caused immunoglobulin concentrations to fall below the normal limit. Based on a cerebrospinal fluid (CSF) sample drawn after infusion, she was found to have an abnormally high IgG index and a high intrathecal IgG synthesis rate. However, clinical correlations ruled out demyelinating disease. Various equations used for the calculation were examined and found to yield false positive results with values of serum IgG below the reference range. Only the Ohman formula provided the correct prediction in this patient. Although hypo- or hyper-albuminemia have little effect on these equations, they may escalate the impact of hypoimmunoglobulinemia. Thus, interpretation of laboratory data under these conditions must be exercised with care.

Adult

The relationship between myocardial blood flow and glucose uptake in ischemic canine myocardium determined with fluorine-18-deoxyglucose.

The relationship between myocardial blood flow as a marker of severity of ischemia and exogenous glucose utilization was examined following occlusion of the left anterior descending coronary artery in 10 fasted, anesthetized, open-chest dogs. Fluorine-18-fluorodeoxyglucose (FDG) was injected 10 min after the onset of ischemia and serial blood samples were obtained to measure FDG in plasma. Tracer-labeled microspheres, used to measure myocardial blood flow (MBF), were injected 10 and 40 min postocclusion. After the last microsphere injection, the heart was arrested and removed rapidly. Tissue samples of the left ventricle were obtained, weighed and FDG counts were determined. Two days later, the same samples were assayed for radioactivity from the tracer-labeled microspheres and blood flow was calculated. Thus, FDG uptake and MBF measurements were made in the same tissue samples. When normalized for variations in blood flow, there were no significant differences in FDG uptake between the subendocardial and subepicardial halves of the tissue samples. FDG uptake was relatively high and uniform in normal myocardium, paralleling the pattern of MBF. In ischemic myocardium, however, FDG uptake and MBF did not vary in parallel. In tissue samples with MBF reduced by up to 80% from control levels, relative FDG uptake increased such that absolute FDG uptake remained at normal or near normal levels. In samples with more severe ischemia, FDG uptake decreased precipitously with additional decrements in MBF. We propose that sufficient glycolytic flux may be sustained to maintain cellular viability when perfusion is above the threshold value. Below the threshold, however, irreversible changes may be initiated.

Animals

Quantification of vascular graft seeding by use of computer-assisted image analysis and genetically modified endothelial cells.

Current methods for the evaluation of retention of endothelial cells seeded on vascular grafts are limited by the inability to specifically identify and quantitate seeded cells on a long-term basis. To address this problem we developed a method of quantification of graft surface coverage using genetic labeling of endothelial cells combined with computer-assisted image analysis. Rabbit aortic endothelial cells were transduced with a marker gene (lac-Z) and seeded on polytetrafluoroethylene grafts. After histochemical staining in which the genetically labeled cells turn blue, computer-assisted image analysis was used to measure the percentage of graft surface covered by the seeded cells. The utility of the method was evaluated by using it to assess the effect on graft coverage of seeded cell density and by precoating with fibronectin. Quantification of surface area coverage was automated and reproducible both between scans and between observers. Use of this method allowed the determination of a linear correlation between cell density in the seeding suspension and graft coverage (r2 = 0.93, p less than 0.0001). The method also permitted confirmation of the positive contribution of fibronectin coating to graft coverage by seeded cells: 73% coverage coated versus 8% coverage uncoated (p less than 0.0001). The ability of this method to specifically identify genetically marked endothelial cells and their progeny makes it attractive for use in studies targeted at optimization of graft coverage in vivo.

Animals

Effect of carbon-11-acetate recirculation on estimates of myocardial oxygen consumption by PET.

Mono- and biexponential fitting of myocardial 11C-acetate kinetics does not account for the effect of recirculating 11C activity following intravenous injection of the tracer. A tracer kinetic model comprising two and three compartments was developed to describe intravascular and myocardial 11C-acetate kinetics defined by PET. This model approach including a correction for 11C-metabolites in blood was validated by correlating the model parameter estimates with directly measured oxygen consumption (MVO2) in 11 closed-chest dog experiments over a wide range of cardiac work. The model parameter k2 closely correlated with oxygen consumption (r = 0.94). This approach was subsequently applied to human studies and k2-related to rate-pressure product (PRP). In comparison to conventional monoexponential fitting of 11C-acetate tissue kinetics, the model approach improved the correlation coefficients of scintigraphic MVO2 estimates and PRP values from 0.61 to 0.91. Thus, analysis of myocardial 11C-acetate and clearance kinetics with a tracer kinetic model corrects for recirculating 11C-activity and may provide more consistent estimates of myocardial oxygen consumption.

Acetates

Development of spinal neurons and tracts in the zebrafish embryo.

We have analyzed pathfinding by growth cones in the spinal cord of the early zebrafish embryo, because it is an extremely simple system. At 18-20 hours of development the spinal cord contains approximately 18 lateral and presumably post-mitotic cell bodies per hemisegment. Of these 8-11 have projected growth cones by 18 hr of development and fall into five classes of neurons (Bernhardt et al., J. Comp. Neurol, preceding paper), including a set of mechanosensory (RB) neurons, three classes of interneurons (DoLA, ascending commissural, and VeLD), and previously characterized primary motor neurons (Eisen et al., '86: Nature 320:269-271). Of these five classes we analyzed pathfinding by the RB, DoLA, early ascending commissural, and VeLD neurons. These neurons are distinguishable at the earliest stages of axonogenesis based on the location of their somata and the number and initial directionality of their growth cones. In each case they follow stereotyped, cell-specific pathways to reach their termination sites. Up through larval stages exuberant axons have not been observed. The longitudinal axons of each neuronal class form bundles in the early cord. This apparently occurs because growth cones extend in close association with the longitudinal axons of the same neuronal class. At later stages spatially discrete commissural tracts are found in the cord suggesting that commissural growth cones may follow earlier commissural axons as well.

Animals

Characterization of the CYP2C5 gene in 21L III/J rabbits. Allelic variation affects the expression of P450IIC5.

Rabbits exhibit two heritable phenotypes, 21L and 21H, with the latter displaying roughly 10-fold higher liver microsomal progesterone 21-hydroxylase activity. The higher activity of the 21H animals reflects the elevated expression of cytochrome P-450 1 (P450IIC5). Breeding studies indicate that this phenotypic difference is linked to allelic CYP2C5 genes (Johnson, E. F., Finlayson, M., Husjsak, C. M., Pendurthi, U. R., and Tukey, R. H. (1989) Arch. Biochem. Biophys. 273, 273-280). In this study, we report on the expression and structure of the CYP2C5 gene in the 21L inbred strain III/J. A cDNA encoding P450IIC5 was generated from III/J rabbit liver mRNA using polymerase chain reaction to amplify this sequence. DNA sequence analysis revealed that the cDNA encoded the same protein as the cDNA cloned previously from a 21H rabbit, demonstrating that structural differences in P450IIC5 do not underlie the phenotypic difference in the expression of 21-hydroxylase activity. DNA sequence analysis of the exons and surrounding intron regions in two III/J genomic clones that encode portions of the CYP2C5 gene showed that the exon sequences were identical to that of the P450IIC5 mRNA and that the codon positions of the exon/intron junctions are conserved with other class II genes. Southern blot analysis of DNA digested with BamHI and probed with a portion of DNA isolated from intron 5 revealed that the gene characterized in this study is an allele of the gene conferring the 21H phenotype. Primer extension analysis with a P450IIC5-specific oligonucleotide demonstrated that the CYP2C5 gene uses several transcriptional start sites in both 21H and 21L rabbits. Analysis of mRNA from livers of 21H and 21L rabbits with the P450IIC5-specific oligonucleotide showed a greater than 20-fold difference in the relative abundance of mRNA, which accounts quantitatively for the phenotypic difference in progesterone 21-hydroxylase activity.

Alleles

Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow.

SQ30217 is a new, technetium-99m-(99mTc) labeled perfusion agent introduced for cardiac imaging. To evaluate the myocardial tracer kinetics, 99mTc-SQ30217, was injected intracoronarily in open-chested dogs under baseline conditions and after administration of intravenous (i.v.) dipyridamole. Myocardial first-pass retention fraction averaged 0.90 +/- 0.04. Clearance of the tracer occurred in a biexponential manner. Sixty-seven percent of retained activity cleared with a half-time of 2.3 +/- 0.6 min, while the residual activity demonstrated slow clearance. The clearance rate of the rapid phase correlated with myocardial blood flow (r = 0.72, p less than 0.001). Myocardial SQ30217 clearance rate following i.v. injection as determined by dynamic imaging with tomography (SPRINT) averaged 21 +/- 4 min and increased to 13 +/- 4 min following dipyridamole. Thus, 99mTc-SQ30217 is a promising flow tracer with high initial myocardial retention and rapid tissue clearance, which allow repeated flow determinations within short time intervals using advanced SPECT technology.

Animals

Slowed saccades in the acquired immunodeficiency syndrome.

We recorded eye movements using infrared oculography in ten patients with the acquired immunodeficiency syndrome (AIDS) and ten control subjects of similar age. Peak saccadic velocity for the AIDS group was significantly lower than that of the control group for both adducting and abducting saccades (P less than .001). Saccadic duration for the AIDS group was significantly greater than that of the controls for both adducting and abducting saccades (P less than .02 for adduction and P less than .01 for abduction). There was no difference in saccadic latencies between the two groups. We add slowed saccades to the ocular motility manifestations of AIDS. Our study indicated that analysis of ocular motility may be of value in providing early detection of neurologic dysfunction, and may also be an important quantitative measure of the responsiveness of patients to different types of potential therapies.

Acquired Immunodeficiency Syndrome

Eskimo plasma constituents, dihomo-gamma-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid inhibit the release of atherogenic mitogens.

Studies in man and laboratory animals suggest that omega 3 polyunsaturated fatty acid constituents of fish oils have antiatherosclerotic properties. We have studied the effects of several such polyunsaturated fatty acids for ability to modify the in vitro release of mitogens from human platelets. Such mitogens may produce the fibro-proliferative component of atherosclerotic plaques. Both 5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) and 4,7,10,13,16,19-docosahexaenoic acid (22:6 omega 3), major constituents of fish oils, inhibited adenosine diphosphate-induced aggregation of platelets and the accompanying release of mitogens. These effects are dose dependent. Linolenic acid (18:3 omega 3), the biosynthetic precursor of eicosapentaenoic acid, also inhibited platelet aggregation and mitogen release. Eicosapentaenoic acid also inhibited mitogen release from human monocyte-derived macrophages, which, in vivo, are an additional source of mitogens during atherogenesis. Potent inhibition of human platelet aggregation and mitogen release was also seen with dihomo-gamma-linolenic acid (8,11,14-eicosatrienoic acid 20:3 omega 6), whose levels are reportedly elevated in Eskimos subsisting on marine diets. We conclude that diets that elevate plasma and/or tissue levels of eicosapentaenoic acid, docosahexaenoic acid and dihomo-gamma-linolenic acid precursor gamma-linolenic acid (18:3 omega 6) may exert antiatherosclerotic effects by inhibiting the release of mitogens from platelets and other cells.

8,11,14-Eicosatrienoic Acid

[Polychemotherapy of undifferentiated small cell bronchial cancer. Long-term results].

Long-term results of 2 studies combining etoposide and adriamycin with cisplatin (CAV) or cyclophosphamide (AVE) in small cell lung cancer indicate a 2-year survival rate of 22% and 18% respectively. The complete response rate 2 years after the onset of chemotherapy was 8% (8/98) : 11% (4/36) with CAV and 5% (4/62) with AVE. Among these 8 patients, 2 had a late relapse and one died of an unrelated cause. The actual long-term survival rate was 6% with CAV and 5% with AVE.

Adult

Intravenous propafenone for termination of reentrant supraventricular tachycardia. A placebo-controlled, randomized, double-blind, crossover study.

To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia.

Adult

Invasive candidal balanitis due to a condom catheter in a neutropenic patient.

A 58-year-old man with acute leukemia had balanitis and penile ulceration due to Candida tropicalis after a condom catheter was used because of urinary incontinence. This case illustrates that condom catheters can be associated with serious complications in neutropenic patients and should be used only when absolutely necessary.

Agranulocytosis