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Biomedical subjects

E A Gardner

Publications and source records attributed to E A Gardner.

At least 19 recordsLinked to original sources

Transcutaneous interruption of ultrasound contrast agents for blood flow evaluation.

RATIONALE AND OBJECTIVES: The ability to create short boluses in targeted arteries with rapid rise times is limited by the transport of bubbles from the venous to arterial portion of the circulation. Acoustic interruption of contrast agent in arteries may create the short boluses necessary for simple wash-in/wash-out measures of blood flow. METHODS: An ultrasound contrast agent was used with spectral Doppler ultrasound to observe contrast interruption in femoral arteries and VX2 carcinoma in a rabbit model. At an upstream location in the femoral artery, single, sinusoidal ultrasound tone bursts at 1.8 MHz with durations of 0.25 to 1 seconds were applied to interrupt the flow of contrast agent injected intravenously. RESULTS: In VX2 carcinoma, bursts as short as 40 cycles produced contrast interruption lasting only one cardiac cycle within the tumor periphery and I(SPPA) <3 W/cm2 produced measurable interruptions. CONCLUSIONS: Acoustic fields applied transcutaneously interrupted flow of contrast agents to form temporally short negative boluses.

Animals

Acoustic generation of intra-arterial contrast boluses.

Microbubbles generated by ultrasonic cavitation in vivo might be useable as flow indicators in some situations instead of injectable contrast agents. Knowledge of those vascular microbubble-generating ultrasonic fields which produce from negligible up to significant damage will help improve guidelines for more effective, safer diagnostic and therapeutic ultrasound. Microbubble boluses have been generated by a 1.8-MHz, focused sound field in the in vivo canine abdominal aorta. Spatial peak acoustic intensities of 19,000 W cm-2 generated microbubble boluses when exposure was longer than 12 ms, whereas intensities greater than 4300 W cm-2 generated a bolus when exposure was for 250 ms. The onset time of these boluses (less than one cardiac cycle) is unachievable with intravenous contrast injection. With optimized waveforms and focusing, acoustic bolus generation may prove to be an effective, minimally invasive method for fast performance of certain selective angiography.

Acoustics

Detection of degradation of magnetic resonance (MR) images: comparison of an automated MR image-quality analysis system with trained human observers.

RATIONALE AND OBJECTIVES: The perceived need for magnetic resonance (MR) imaging quality control (QC) is occasionally minimized on the assumption that significant errors will be detected by the users. To evaluate the validity of this assumption, we compared the sensitivity of a test object and automated image analysis system for MR imaging QC with the sensitivity of trained human observers by evaluating images that were intentionally degraded. METHODS: Parameters for imaging the test object and normal human volunteers were set to values that decreased the signal-to-noise ratio (SNR), caused distortion, and increased the slice thickness and separation. RESULTS: The human observers were able to detect a 6-13% reduction in the SNR and distortions of more than 15% in human images. They were unable to identify 40% increases in the slice thickness. Automated analysis of test object images was able to detect all image degradations at the minimum levels applied. CONCLUSION: The poor sensitivity of the human observers indicated that degradation, especially spatial measurements, could be significantly in error before being detected through visual analysis of clinical images. These errors would be detected by automated analysis of the test object used. Further investigation is needed to better define the accuracy with which quantitative image-quality analysis predicts the effects of degraded image quality on the ability of human observers to detect subtle abnormalities in clinical images.

Contrast Sensitivity

MRI scanner variability studies using a semi-automated analysis system.

Due to the unique design of the Parallel Rod Test Object (PRoTO) and the associated semi-automated analysis program, it was necessary to test it extensively for precision and accuracy, and preliminarily for utility, before its distribution for wider use in MRI system quality control (QC). The test object and analysis program measured the desired quantities reproducibly and they accurately measured predicted changes from intentionally adjusted imaging system parameters, yielding sensitivity of the various test measures to deviation in the system operating parameters. From a single scan of the most recent revision of the test object, multiple quantitative quality control measures were obtained throughout the scanning volume on two MR imaging systems over periods of six and twelve months, respectively. From these and earlier trials, an initial indication was obtained of which performance measures are worth monitoring for QC. This experience suggests that signal-to-noise ratio (SNR) and distortion (including display scale) should be monitored but not necessarily the resolution. The latter was only found to alter at the same time or later than other parameters such as SNR had changed. Slice thickness was found to vary on some units and this measure was also used in normalizing the SNR by voxel volume. SNR, distortion, and resolution measurements using field-echo sequences were less stable than those using spin-echo sequences. Use of this QC program to test a wide variety of image quality measures allowed timely assessment of the long-term variability of the units tested. Long-term variability may become among the most important measures for comparison of system performance and maintenance.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts

Improvement in fluoxetine-associated sexual dysfunction in patients switched to bupropion.

BACKGROUND: This study was conducted to determine the effect of bupropion on the sexual functioning of male and female outpatients who developed anorgasmia or delayed orgasm while receiving fluoxetine treatment for depression. METHOD: Thirty-nine patients who satisfied criteria for participation in the study discontinued fluoxetine treatment and entered a 2-week washout phase followed by an open 8-week bupropion treatment phase. Three parameters of sexual functioning were followed throughout the study: orgasm function, libido, and satisfaction with overall sexual functioning. Depression was also evaluated at each visit. RESULTS: All patients reported orgasm delay and/or failure at the time of fluoxetine discontinuation. Orgasm function, libido, and satisfaction with sexual functioning improved during the 2-week fluoxetine washout period and during the bupropion treatment phase. Ninety-four percent of patients (29/31) had complete or partial resolution of their orgasm dysfunction at the end of bupropion treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied with their overall sexual functioning. Most patients entered the study with decreased libido on fluoxetine. Libido was "much" or "very much" increased for 81% of patients (25/31) at the end of the study. In addition, depression scores on the Hamilton Rating Scale for Depression and Clinical Global Impressions-Severity scale significantly improved during the bupropion treatment phase. Finally, bupropion was well tolerated by most patients. CONCLUSION: Bupropion may be an appropriate antidepressant for patients who develop sexual dysfunction during fluoxetine treatment or for whom sexual dysfunction is a concern.

Ambulatory Care

Limbic system dysrhythmia: a diagnostic electroencephalogram procedure utilizing procaine activation.

A diagnostic method is presented that makes it possible to distinguish patients who are most likely to show a positive response to treatment with anticonvulsant medication, thereby cutting across many DSM-III-R diagnoses. Patients are evaluated to determine whether they exhibit at least 4 of 12 groups of symptoms, and the local anesthetic procaine is used, along with an electroencephalogram (EEG) to evaluate for omega band activity (30-50 Hz) of at least 50 microvolts or approximately three times baseline values in the anterior temporal leads. This method was studied in 145 patients with varying diagnoses. Eighty-three percent of patients who were symptom- and procaine-positive responded to anticonvulsants. Specific application to patients with attention-deficit hyperactivity disorder, bipolar disorder, and panic disorder is made. This method may provide a basis for identifying subpopulations of anticonvulsant-responsive patients who often are considered treatment-resistant.

Adolescent

Double-blind comparison of bupropion and fluoxetine in depressed outpatients.

BACKGROUND: This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine. METHOD: Moderately to severely depressed outpatients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression (21 item) participated in this two-center study. Following a 1-week placebo phase, patients were randomly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment. Weekly efficacy assessments included Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. Vital signs and adverse experiences were also assessed weekly. RESULTS: A total of 61 patients were randomly assigned to receive bupropion (225-450 mg/day) and 62 were randomly assigned to receive fluoxetine (20-80 mg/day). The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group. There were no statistically significant differences between treatments on any of the efficacy variables. On the basis of a 50% or greater reduction in the HAM-D scores, 63% (N = 37) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were categorized as responders, and on the basis of CGI scores, 68% (N = 40) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were rated as much or very much improved. HAM-A scores decreased by 59% for both treatment groups. The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments. Twenty-six percent (N = 16) of the bupropion-treated and 29% (N = 18) of the fluoxetine-treated patients prematurely discontinued treatment. CONCLUSION: Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety, and both exhibited a similar, favorable safety profile.

Adult

Body image of sexually and physically abused children.

Body size perception was measured in 41 children aged 6-10 who had been either sexually or physically abused, or had no history of abuse. Two psychophysical methods were used, including the staircase method and a signal detection method. In the staircase methodology, children adjusted the direction of distortion of their continuously changing body size. In the signal detection method, children made judgments about the presence or absence of size distortion in presented images. Results using the staircase method indicated children overestimated their body sizes, with no differences between abuse conditions, gender, or age. For the signal detection methodology, no difference in ability to detect the presence/absence of size distortion (d') was found between abuse conditions, although females were less accurate than males. All groups were better able to detect distortion when the image was distorted too wide. Measures of response bias (Ln beta) indicated that sexually abused children had a greater bias to report size distortion as present, as compared with the physically abused children.

Body Image

Bupropion--an antidepressant without sexual pathophysiological action.

Bupropion, a new nontricyclic antidepressant, was administered clinically on an open basis to 40 male outpatients at doses of 300 to 600 mg/day for 4 to 26 months. Of these, 12 patients had no history of sexual dysfunction, whereas 28 patients reported a history of significant sexual dysfunction (impaired libido, partial erection) while receiving tricyclic, monoamine oxidase inhibitor, maprotiline, and trazodone antidepressants. The adverse sexual effects resolved in 24 of the 28 patients (p less than 0.001) when they were transferred to bupropion. Of the four patients who failed to improve sexually on bupropion, two were diabetic and the other two had lifelong impairments in sexual functioning that were probably unrelated to drugs or depression. The 12 patients who had a negative history of sexual dysfunction continued to have normal sexual functioning during bupropion treatment. Based upon bupropion's lack of anticholinergic and antiadrenergic effects and the clinical observations in this study, this antidepressant appears to have a very low propensity for inducing adverse sexual side effects.

Adult

Long-term preventive care in depression: the use of bupropion in patients intolerant of other antidepressants.

The safety and efficacy of bupropion in the preventive care of depression was studied in a long-term open trial. Forty patients from an active general psychiatric practice which emphasizes the treatment of affective disorders have been followed for an average of 336 days (range, 44-791) and seen at least monthly for evaluation with the Hamilton Depression Scale, Zung Self-Rating Scales for Depression and Anxiety, Clinical Global Impression Scale and an adverse reaction report form. One third of the patients had received a diagnosis of bipolar disorder and 50% a diagnosis of recurrent major depressive disorder by DSM-III criteria; all patients were intolerant of tricyclic and other antidepressants. Although several patients were not severely depressed when placed on bupropion, there was a significant improvement on the Zung Self-Rating Scales. There was a striking reduction in the frequency and intensity of adverse reactions, particularly anticholinergic effects, appetite and weight gain, and sexual dysfunction, compared to tricyclics. Also, there were no cardiovascular changes and no physical, ECG, EEG, or laboratory evidence of toxicity. Bupropion represents a significant advance in the treatment of depression, particularly for patients who require long-term preventive care and in whom adverse reactions, which might be tolerated in acute treatment, may lead to noncompliance.

Adult

Evidence for convertible forms of soluble uterine cyclic nucleotide phosphodiesterase.

The cyclic nucleotide phosphodiesterase (3':5'-cyclic nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) systems of many tissues show multiple physical and kinetic forms. In contrast, the soluble rat uterine phosphodiesterase exists as a single enzyme form with non-linear Lineweaver-Burk kinetics for cyclic AMP (app. Km of approx. 3 and 20 microM) and linear kinetics for cyclic GMP (app. Km of approx. 3 microM) since the two hydrolytic activities are not separated by a variety of techniques. In uterine cytosolic fractions, cyclic AMP is a non-competitive inhibitor of cyclic GMP hydrolysis (Ki approx. 32 microM). Also, cyclic GMP is a non-competitive inhibitor of cyclic AMP hydrolysis (Ki approx 16 microM) at low cyclic GMP/cyclic AMP substrate ratios. However, cyclic GMP acts as a competitive inhibitor of cyclic AMP phosphodiesterase (Ki approx 34 microM) at high cyclic GMP/cyclic AMP substrate ratios. When a single hydrolytic form of uterine phosphodiesterase, separated initially by DEAE anion-exchange chromatography, is treated with trypsin (0.5 microgram/ml for 2 min) and rechromatographed on DEAE-Sephacel, two major forms of phosphodiesterase are revealed. One form elutes at 0.3 M NaOAc- and displays anomalous kinetics for cyclic AMP hydrolysis (app. Km of 2 and 20 microM) and linear kinetics for cyclic GMP (app. Km approx. 5 microM), kinetic profiles which are similar to those of the uterine cytosolic preparations. A second form of phosphodiesterase elutes at 0.6 M NaOAc- and displays a higher apparent affinity for cyclic AMP (app. Km approx. 1.5 mu) without appreciable cyclic GMP hydrolytic activity. These data provide kinetic and structural evidence that uterine phosphodiesterase contains distinct catalytic sites for cyclic AMP and cyclic GMP. Moreover, they provide further documentation that the multiple forms of cyclic nucleotide phosphodiesterase in mammalian tissues may be conversions from a single enzyme species.

3',5'-Cyclic-AMP Phosphodiesterases

Activation of mammalian cyclic AMP phosphodiesterases by trypsin.

BHK fibroblasts contain two forms of cyclic AMP phosphodiesterase 3':5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) as analyzed by linear sucrose gradient fractionation; a 3.6-S form (peak I) and a 6.7-S form (peak II). Peak I is specific for cyclic AMP as substrate and displays Michaelis-Menten kinetics with an apparent Km of 2--3 micrometer. Peak II hydrolyzes cyclic GMP and displays anomalous kinetics for cyclic AMP hydrolysis. The activity of isolated peak II for cyclic AMP is increased by storage at 4 degrees C, treatment with trypsin, or treatment with rat brain and BHK fibroblast activator proteins. The activity of isolated peak I is unaffected by these conditions. Linear sucrose gradient fractionation demonstrates that activation of peak II by trypsin leads to the formation of a 3.6-S cyclic AMP-specific enzyme form, possibly peak I. In contrast to BHK fibroblasts (and most other mammalian tissues), rat uterus contains only one form of cyclic nucleotide phosphodiesterase on linear sucrose gradients, a 7-S form capable of hydrolyzing both cyclic AMP and cyclic GMP. Treatment of rat uterine supernatant with trypsin leads to the appearance of a 4-S, cyclic AMP-specific form with properties similar to that of BHK peak I. These data suggest that the kinetically complex, higher molecular weight cyclic nucleotide phosphodiesterases may consist of more than one catalytically active site and that multiple forms of the enzyme arise through dissociative mechanisms, possibly as a means of in vivo regulation.

3',5'-Cyclic-AMP Phosphodiesterases

Characterization of soluble uterine cyclic nucleotide phosphodiesterase.

Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP.

3',5'-Cyclic-AMP Phosphodiesterases

Perifused adipose cells, quantitation and kinetics of lipolysis.

The perifused fat cell system is a system with which lipolytic activity can be monitored on a minute-to-minute basis. Thus, the rate at which lipolysis changes following the addition and removal of hormones can be followed. Catecholamines and other lipolytic agents produced a time-dependent increase in lipolysis following addition of agents, and a time-dependent decrease in lipolysis occurred following removal of the agent. ACTH also produced an increase in lipolysis. However, on termination of ACTH infusion, the lipolytic rate did not return to basal level but remained elevated for at least an additional 30 min (persistent phase). The persistent phase could be terminated by removal of Ca2+. Readdition of Ca2+ in the absence of additional ACTH resulted in a rapid increase in glycerol release. No persistant phase occurred following ACTH if the adipocytes were perifused in a Ca2+-free buffer. However, if Ca2+ was added to the system 20 min after termination of ACTH infusion, lipolysis increased to a rate greater than that obtained initially by infusing ACTH in a Ca2+-free buffer. It is concluded that ACTH is bound to some component of the fat cell in a Ca2+ independent, tenacious manner, and the full manifestation of that binding is dependent on the presence of Ca2+.

Adipose Tissue