Treatment of major depression: selection of initial drug.
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Antidepressive Agents↗
Biomedical subjects
M E Schmidt
Publications and source records attributed to M E Schmidt.
Acute alpha 2 blockade by idazoxan increases insulin and lowers plasma glucose during positron emission tomography.
The sympathetic nervous system can modulate glucose levels through a variety of mechanisms, including inhibition of insulin release by alpha2-adrenergic receptors. Such effects could potentially confound measurements of brain glucose metabolism during studies of the central actions of sympathomimetic drugs. Plasma glucose, insulin, and sympathetic responses to alpha2 blockade were measured following infusion of idazoxan, a selective alpha2 antagonist, or placebo, in 33 healthy volunteers (idazoxan: n = 23, placebo: n = 10). These measures were compared with estimates of global brain metabolism obtained from positron emission tomography (PET) scans before and after the infusion. Glucose levels fell and fractional levels of insulin rose after idazoxan, compared with placebo. Relative increases in insulin correlated with increases in epinephrine after active drug. The increases in insulin are consistent with the hypothesized role of alpha2-adrenoceptors in regulating insulin release. Estimates of global brain glucose metabolism did not appear to be influenced by the modest changes in plasma glucose.
Adrenergic alpha-2 Receptor Antagonists↗
Cerebral glucose metabolism during pharmacologic studies: test-retest under placebo conditions.
UNLABELLED: The reliability of serial [18F]fluorodeoxyglucose (FDG) PET scans for psychopharmacologic studies was tested by using placebo infusions. METHODS: FDG scans were obtained before and after a 30 min placebo infusion (n = 10; Group 1) or after each of two bolus infusions with placebo (n = 8; Group 2). Subjects performed a continuous performance task (CPT) during each scan. Cardiovascular measures and ratings of anxiety were obtained in all subjects. Samples for determination of plasma norepinephrine (NE) were taken at multiple time points in Group 1. RESULTS: A slight increase in apparent global metabolism occurred between scans in both Groups 1 and 2. A few regions significantly increased in both groups. While an apparent increase in sympathetic activity occurred during the placebo infusion, neither NE levels, anxiety ratings nor cardiovascular measures correlated with global or regional FD6 uptake. CONCLUSION: Test-retest differences of global and regional glucose metabolism were highly consistent across two experimental designs. While increases in cerebral glucose metabolism appeared to occur during the second scan, differences between scans were small. This method may offer advantages for selected psychopharmacologic studies.
Adult↗
Regional brain glucose metabolism after acute alpha 2-blockade by idazoxan.
BACKGROUND: Several classes of antidepressant drugs act on alpha 2-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha 2-binding and in vivo responses mediated by alpha 2-receptors. Measurement of regional brain metabolic response to an alpha 2-antagonist may be a useful method for further definition of the role alpha 2-receptor regulation plays in the treatment of neuropsychiatric disorders. METHODS: Regional brain glucose metabolism was measured before and after infusion with 200 micrograms/kg idazoxan with use of 18F-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured. RESULTS: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response. CONCLUSIONS: Our findings are consistent with regionally specific effects of alpha 2-blockade. This method may be useful for the study of alpha 2-receptor function in humans.
Adrenergic alpha-Antagonists↗
The effects of prolonged lithium exposure on the immune system of normal control subjects: serial serum soluble interleukin-2 receptor and antithyroid antibody measurements.
The purpose of this study was to begin evaluating the effects of lithium carbonate on in vivo immune function in normal controls. We postulated that lithium carbonate would stimulate lymphocytes but would not affect the production of antithyroid antibodies. Twenty-seven normal controls had blood samples drawn for measurements of serum soluble interleukin-2 receptors (SIL-2Rs), antithyroglobulin antibodies, and antimicrosomal antibodies prior to and after approximately 1 and 4 weeks of treatment with lithium carbonate at therapeutic blood levels. Subjects had a small but statistically significant increase in serum SIL-2Rs after 4 weeks of lithium treatment (446.3 +/- 177.2 U/ml versus 497.6 +/- 232.3 U/ml, p = 0.033). There was no increase in the prevalence of antithyroglobulin or antimicrosomal antibodies with lithium treatment nor did lithium act as an adjuvant to increase the titers in subjects with preexisting antithyroid antibodies.
Administration, Oral↗
Clostridium difficile colitis associated with trimethoprim-sulfamethoxazole given as prophylaxis for Pneumocystis carinii pneumonia.
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AIDS-Related Opportunistic Infections↗
Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys.
Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.
Attention Deficit Disorder with Hyperactivity↗
Endophthalmitis caused by unusual gram-negative bacilli: three case reports and review.
Endophthalmitis due to gram-negative bacilli has been associated with a high degree of vision loss. We report three cases due to the nonenteric gram-negative bacilli Moraxella nonliquefaciens, Haemophilus paraphrophilus, and multidrug-resistant Haemophilus influenzae. The features of these cases are compared with those of other reported cases of endophthalmitis due to unusual nonenteric gram-negative bacilli. Fifty-eight percent of patients had no vision in the affected eye after treatment. Early surgical intervention with vitrectomy and intravitreous antibiotics in addition to parenteral antibiotics should be included in the treatment of endophthalmitis due to gram-negative bacilli.
Actinobacillus Infections↗
Rapidly progressive penile ulcer: an unusual manifestation of Kaposi's sarcoma.
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Adult↗
Urinary free cortisol output and disruptive behavior in children.
Hostile, impulsive, and aggressive behaviors have been associated with decreased urinary free cortisol (UFC) output. This is the first study to assess 24-hour UFC output in disruptive behavior disorders. The UFC of 19 boys with attention deficit and/or conduct disorder was compared with that of 19 age, race, and IQ matched normal controls studied as inpatients. Continuous Performance Test scores showed greater impulsivity in the disruptive group. UFC output did not differ between groups. However, UFC and difficulty were positively correlated on the continuous performance test in the form of longer interstimulus intervals and longer reaction times.
Adolescent↗
Clinal genetic variation at enzyme loci in bald eagles (Haliaeetus leucocephalus) from the western United States.
Five polymorphic enzyme loci of about 50 sampled were discovered in blood extracts of bald eagles from Alaska, Washington, Oregon, and Arizona, representing the first biochemical genetic variation described for the species. All five loci exhibited trends of north-to-south clinal geographic variation in gene frequencies. Gene frequencies at three loci culminated in fixation in the Arizona population, which consists of 12 known breeding pairs. The Arizona birds were maximally heterozygous at the other two loci, suggesting the possibility of maintenance of some clines by natural selection. No significant discontinuities in gene frequencies were observed which correlated with earlier descriptions of two subspecies (northern and southern races) of bald eagles.
Animals↗
Effects of polynucleotides and levamisole on alveolar macrophage morphology and receptor activity.
Incubation of rabbit pulmonary alveolar macrophages in vitro with polyinosinic acid-polycytidylic acid [poly(I-C)] or levamisole results in enhanced immunoglobulin G receptor activity in comparison to untreated cells, Electron microscopy of cells treated with levamisole or poly(I-C) revealed mitochondrial swelling and cytoplasmic vacuolization. The modulation of receptor activity by these agents suggests that their immunopotentiating effects are due to direct simulation of the mononuclear phagocyte system. Lavaged alveolar macrophages have the capacity to change membrane function in vitro, and these cells provide a convenient system for studying agents with potential effects on macrophages.
Animals↗
Monocyte IgG receptor activity, dynamics, and modulation-normal individuals and patients with granulomatous diseases.
Studies of monocyte IgG receptor activity by tritration of rabbit Forssman antibody and fluid phase inhibition with human IgG1 and IgG3 indicate increased activity for cells from patients with sarcoidosis in comparison to normal individuals. IgG receptor activity was also increased for cells from patients with tuberculosis and, to some degree, for Crohn's disease patients. Monocyte C3 receptor activity is increased in sarcoidosis and Crohn's disease. Following phagocytosis of latex particles, IgG receptor activity remains for monocytes from sarcoidosis patients, whereas activity transiently disappears for monocytes from normal individuals. Incubation with multistranded polynucleotides increases IgG receptor activity for normal subjects and has no significant effect on cells from patients with sarcoidosis or Crohn's disease. The findings suggest that circulating monocytes from patients with sarcoidosis, Crohn's disease, and tuberculosis are activated in vivo as reflected by increased IgG and C3 receptor activity.
Binding Sites, Antibody↗
Nephrotoxic action of rattlesnake and sea snake venoms: an electron-microscopic study.
The fine structure of renal corpuscles and proximal convoluted tubules of the right kidneys of Suiss mice were studied 9 hr after the injection of the venom of Crotalus atrox (Western diamond-back rattlesnake) or the venom of Laticauda semifasciata (broad-banded blue sea snake). Rattlesnake envenomation resulted in several ultrastructural changes in the renal corpuscles and proximal convoluted tubules. Visceral epithelial changes included intracellular oedema, blebbing, vesiculations, the formation of microvillus projections and dilatation of the endoplasmic reticulum and mitochondria. Changes in the parietal epithelium were similar except that no microvillus projections were noted. Mesangiolysis was a consistent finding. Collagenous fibrils were very prominent in the lysed areas of the mesangial cells. Increased numbers of lysosome-related structures were noted in the proximal convoluted tubule cells. Most of the nuclear cisternae of the cells of the renal corpuscles and proximal convoluted tubules were greatly dilated. Sea snake envenomation resulted in focal organellar swelling and focal intracellular oedema of the visceral epithelium. This venom did not affect the cells of the proximal convoluted tubule. The presence of light and dark visceral epithelial cells has been a consistent finding for both the control and the environmated groups.
Animals↗
Effects of levamisole on human monocyte function and immunoprotein receptors.
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Binding Sites, Antibody↗
Variations in kidney ultrastructure with a variety of paraformaldehyde fixation techniques.
Variations in fine structure of glomeruli and proximal tubules were studied to determine the results of several fixation techniques with paraformaldehyde. Immersion fixation techniques generally resulted in poor fixation, while the quality of fixation by perfusion was directly related to the concentration of the paraformaldehyde. The best technique was fixation by perfusion and immersion in 3% paraformaldehyde for 2 h followed by a post-fixation in 1% OsO4 for 1 h. Intracellular edema was noted in all epithelial, mesangial and proximal tubular cells that were from poorly fixed kidneys. Swollen mitochondria and the dilated endoplasmic reticulum were common in many of those cells. Mesangial and proximal tubular cells were the first to swell. Poor fixation produced the early stages of autolysis. The criteria for good paraformaldehyde fixation are discussed.
Animals↗
Effects of synthetic single- and multistranded polynucleotides on human monocyte IgG receptor activity in vitro.
Human peripheral monocytes demonstrated a higher IgG receptor activity in vitro after incubation with multistranded polynucleotides (poly(I:C) and poly(I:C:U)) after 6-hr cultivation periods. These changes were most pronounced using SRBC coated with low anti-Forssman antibody concentrations (EA, 1:1600 and 1:6400). Polyinosinic and polycytidylic acids failed to show changes in receptor activity. These findings suggest monocyte activation in vitro by multistranded polynucleotides and may in part explain their antitumor activity.
Cell Membrane↗