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M E Schmidt

Publications and source records attributed to M E Schmidt.

At least 19 recordsLinked to original sources
PubMed2001

Test-retest reliability of DSC MRI CBV mapping in healthy volunteers.

Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) can be used to generate high resolution maps of cerebral blood volume (CBV). To determine the test-retest reliability, CBV was measured in eight volunteers on two occasions, separated by 4 weeks. The mean ratio (scan 2/scan 1) for 72 cortical regions of interest (ROIs) was 1.03, with a coefficient of variation of 14%. The correlation between the first and second scans was 0.73 (p < 0.0001; 95%). In five hand-drawn ROIs, the mean ratio was 1.08, with a coefficient of variation of 12%. The correlation between scans was 0.84 (p < 0.0001). The data presented here support the hypothesis that DSC MRI CBV mapping has acceptable test-retest reliability.

Adult↗
PubMed2001

The effects of ECT on brain glucose: a pilot FDG PET study.

BACKGROUND: Regional brain activity was measured before and after electroconvulsive therapy (ECT) using [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET). METHODS: 6 patients (4 females) with major depression were free of psychotropic medications for at least 2 weeks prior to baseline FDG scans. Patients were treated with bifrontotemporal ECT, and posttreatment scans were obtained after the last treatment. RESULTS: A region of interest (ROI) analysis of absolute metabolic rate showed a decrease in CMRglu after ECT in all 61 regions examined. In 17 of the 61 regions, the decrease was significant at the p < 0.05 level. In the right parietal lobe, and the right anterior and left posterior frontal lobes, the decrease in CMRglu significantly correlated with the decrease in Hamilton Depression Rating Scale (HDRS) scores (r = 0.83, 0.82, and 0.84, respectively). The analysis of CMRglu normalized to global metabolic rate showed significant increases in 8 of 61 regions, including basal ganglia, upper brainstem, and occipital lobe. DISCUSSION: The decreases in global glucose metabolism and correlation of changes in frontal metabolism with decreases in HDRS are consistent with earlier brain imaging studies of ECT. The relative increases in CMRglu observed in regions with known dopaminergic innervation (caudate and upper brainstem) have not been previously reported.

Adult↗
PubMed2000

Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study.

OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.

Adult↗
PubMed2000

Aspergillus and endobronchial abnormalities in lung transplant recipients.

STUDY OBJECTIVE: To determine the relationship between aspergillus recovery from the airways of lung transplant recipients and the development of endobronchial abnormalities. DESIGN: Retrospective case series. SETTING: Tertiary-care hospital. PATIENTS: All patients who underwent lung transplantation between December 1991 and June 1999. MEASUREMENTS AND RESULTS: The study cohort included 38 patients. The primary end point was the bronchoscopic identification of an endobronchial abnormality. Aspergillus was isolated from the lungs of nine patients (23.7%). Most of these isolates occurred early after transplantation (mean, 8 weeks). Endobronchial abnormalities arose in seven of the patients (18.4%) and manifested as either exuberant granulation tissue or stricture formation. Six of the 9 (66.6%) patients with aspergillus developed airway lesions, compared to 1 of the 29 patients (3.4%) without aspergillus (p = 0.0002). Endobronchial abnormalities were 19.3 times more likely to occur in patients in whom aspergillus had previously been isolated. As a screening test for the subsequent diagnosis of an airway complication, the recovery of aspergillus had a sensitivity and specificity of 85.7% and 90.3%, respectively. These aspergillus-related endobronchial abnormalities were clinically relevant as evidenced by a mean increase of 25.9% in the FEV(1) after bronchoscopic intervention. CONCLUSION: The early isolation of aspergillus from the airways of lung transplant recipients identifies patients at increased risk for the development of clinically significant endobronchial abnormalities.

Aspergillosis↗
PubMed2000

The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder.

BACKGROUND: A simple, once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression. Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment. The safety and effectiveness of a new formulation of enteric-coated fluoxetine (90 mg) given once weekly was tested during the continuation treatment of major depressive disorder. METHOD: Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores > or = 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores > or = 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responders (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, placebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. The primary efficacy measure was the percentage of patients who relapsed. Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates. Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscales by last observation carried forward (LOCF). Safety measures included comparison of treatment-emergent adverse events, both spontaneous and solicited (using the Association for Methodology of Documentation in Psychiatry-Module 5), vital signs, and laboratory measures. RESULTS: Relapse rates for patients assigned to fluoxetine, either 20 mg daily or 90 mg weekly, were significantly lower than for placebo by log-rank analysis and LOCF analyses of secondary efficacy measures. Efficacy did not significantly differ between the 2 active drug groups by these measures. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated, and its safety profile was similar to that of daily 20 mg of fluoxetine. CONCLUSION: The formulation of enteric-coated fluoxetine taken once weekly is effective, safe, and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine. Monitoring during long-term treatment for evidence of sustained remission is important regardless of dosing regimen.

Adolescent↗
PubMed2000

Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder.

BACKGROUND: A new formulation of enteric-coated fluoxetine given once weekly could be a useful option for the long-term treatment of depression, but compliance to once-weekly fluoxetine treatment has not been assessed. METHOD: Patients were adults from the United Kingdom who had responded to fluoxetine treatment for a current episode of depression (DSM-IV criteria). In the baseline assessment phase, all patients (N = 117) were continued on 20 mg of open-label fluoxetine once daily for 4 weeks. In the follow-up phase, patients (N = 109) were randomly assigned to once-weekly or once-daily fluoxetine for 3 months. Patient compliance was monitored by electronic devices during both phases of the study. RESULTS: Compliance to once-weekly fluoxetine treatment was higher than compliance to once-daily fluoxetine (85.9% vs. 79.4%, respectively). CONCLUSION: Once-weekly fluoxetine treatment allows for new flexibility for both the clinician and the patient, and this study alleviates the concern that patients will forget weekly doses.

Adult↗
PubMed1999

Cerebral glucose metabolic and plasma catecholamine responses to the alpha(2) adrenoceptor antagonist ethoxyidazoxan given to healthy volunteers.

RATIONALE: Methods that test for the central effects of alpha(2)-adrenoceptor antagonists can facilitate the clinical development of such compounds. Recently we evaluated the effects of idazoxan (IDX), an alpha(2)-adrenoceptor antagonist with high affinity for imidazoline sites, on a variety of measures potentially sensitive to blockade of alpha(2)-adrenoceptors including regional brain glucose metabolic rate. OBJECTIVE: To test whether these effects on brain metabolic rate could have been mediated by imidazoline binding sites, single dose challenges of 9 or 12 mcg/kg ethoxyidazoxan (ETX; an alpha(2)-adrenoceptor antagonist which does not bind to imidazoline sites) were given to healthy male volunteers. METHODS: The effects on brain glucose metabolism, blood pressure, catecholamines, and behavior were assessed. RESULTS: Blood pressure increased 10-15% after both doses. Plasma catecholamines increased 2- to 2.5-fold and responses were dose dependent. There was no evidence of either dose being anxiogenic. Both doses of ETX produced diffuse increases in brain glucose metabolism. CONCLUSIONS: Brain glucose metabolic responses were more widespread and monotonic than we had observed with IDX. ETX also produced robust increases in glucose metabolism in cerebellum. While we were unable to exclude the possibility that some of the brain metabolic responses we had observed with IDX were mediated by imidazoline sites, ETX may be sufficiently distinct from IDX in alpha(2)-adrenoceptor affinity that differences in acute metabolic responses occurred.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1999

Aspects of fetal thyroid dose following iodine-131 administration during early stages of pregnancy in patients suffering from benign thyroid disorders.

Detrimental effects on the thyroid of the developing fetus as a result of iodine-131 treatment for thyrotoxicosis of the mother in the first trimester of pregnancy are discussed. Dose estimations under typical clinical circumstances yield a fetal thyroid dose of 100- 450 Sv. This dose may increase considerably if the blood concentration of (131)I in the mother remains high. Under such circumstances there may be fetal thyroid dysfunction, which can lead to severe abnormalities.

Abnormalities, Radiation-Induced↗
PubMed1999

Direct correlation between hyperoxaluria/oxalate stone disease and the absence of the gastrointestinal tract-dwelling bacterium Oxalobacter formigenes: possible prevention by gut recolonization or enzyme replacement therapy.

Oxalobacter formigenes is a specific oxalate-degrading, anaerobic bacterium inhabiting the gastrointestinal tracts of vertebrates, including humans. This bacterium maintains an important symbiotic relationship with its host by regulating oxalate homeostasis, primarily by preventing enteric absorption. Increased absorption of oxalate can lead to multiple complications associated with hyperoxaluria, especially recurrent calcium oxalate urolithiasis. Detection of O. formigenes in the gastrointestinal tract has attracted attention because the absence of this bacterium appears to be a risk factor for development of hyperoxaluria and/or recurrent calcium oxalate kidney stone disease. In the present study, epidemiologic studies with patients at high risk for calcium oxalate urolithiasis showed a direct correlation between the number of recurrent kidney stone episodes and the lack of O. formigenes colonization. As expected, the lack of O. formigenes revealed a clear association with prophylactic antibiotic therapy. To confirm the importance of O. formigenes in regulating hyperoxaluria, laboratory rats known to be noncolonized were colonized with live bacteria or treated with a preparation of oxalate-degrading enzymes derived from O. formigenes to determine any subsequent increased resistance to high oxalate challenge. Rats receiving either bacteria or enzyme replacement therapy excreted far lower levels of oxalate, did not develop the crystalluria observed with control rats, and resisted the formation of calcium oxalate crystals in their nephrons. These observations, taken together, support the concept that O. formigenes is important in maintaining oxalate homeostasis, that its absence from the gut increases the risk for hyperoxaluria and recurrent kidney stone disease, and that replacement therapy is an efficient procedure to prevent hyperoxaluria and its complications.

Adult↗
PubMed1998

Foveal outer retinal function in eyes with unexplained visual symptoms or acuity loss.

OBJECTIVE: To determine whether foveal outer retinal dysfunction is common in eyes with unexplained visual symptoms or acuity loss. DESIGN: Prospective study. PARTICIPANTS: Seventy-three eyes of 44 consecutive patients with unexplained visual symptoms or acuity loss, 39 eyes of 39 control subjects, and 12 eyes of 7 patients with known maculopathy. INTERVENTION: Foveal cone electroretinography (ERG) and letter recognition perimetry. MAIN OUTCOME MEASURES: Foveal cone ERG data. RESULTS: Abnormal foveal cone ERG data were recorded in 35 (48%) of 73 eyes (23 [52%] of 44 patients). Among these 35 eyes, amplitude was lower than in normal controls (P<.001) and was correlated with visual acuity and the number of letter recognition perimetry errors (P<.05 for both). The latter was higher in eyes with abnormal retinal responses than in symptomatic eyes with normal responses (P<.01). However, initial symptoms, visual acuity, and macular appearance did not differentiate between these 2 groups. Foveal cone ERG test vs retest data showed consistent results. CONCLUSION: Foveal outer retinal dysfunction is a common underlying mechanism of previously unexplained visual symptoms or acuity loss. Foveal cone ERG testing should be considered early in the evaluation of eyes with this presentation.

Adolescent↗
PubMed1997

Responses to alpha 2-adrenoceptor blockade by idazoxan in healthy male and female volunteers.

Seven male and five female volunteers underwent double-blind infusions of the alpha 2-adrenoceptor antagonist idazoxan (100 and 200 micrograms/mg) and placebo in random order. Blood pressure, plasma norepinephrine, growth hormone and subjective responses were measured. The higher dose of idazoxan produced increases in blood pressure, norepinephrine and growth hormone and slight increases in anxiety. Both subject age and sex appeared to influence the magnitude of responses.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1997

Gender differences in brain metabolic and plasma catecholamine responses to alpha 2-adrenoceptor blockade.

alpha 2-Adrenergic receptors modulate the release of several neurotransmitters implicated in the treatment and pathophysiology of mood and anxiety disorders. Significant sex differences occur in the prevalence of both disorders. To test whether gender affects alpha 2 function, the plasma catecholamine and brain metabolic responses to alpha 2 blockade were measured in male and female volunteers. Ten female and thirteen male volunteers underwent [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans before and after infusion of idazoxan (200 micrograms/kg). Measures of plasma catecholamines, blood pressure, and anxiety were obtained. Norepinephrine responses were larger in males. Women showed global increases in metabolism, whereas males had no global changes and some regional decreases in FDG uptake following idazoxan administration. The differences in norepinephrine increases are consistent with previously reported effects of gender on sympathetic activation. The PET data suggest gender differences in responses to alpha 2-receptor blockade in brain as well.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1997

HIV update.

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Anti-HIV Agents↗
PubMed1997

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↗
PubMed1996

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↗