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Biomedical subjects

E A Gardner

Publications and source records attributed to E A Gardner.

6 recordsLinked to original sources

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

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