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Biomedical subjects

L M Nagy

Publications and source records attributed to L M Nagy.

30 records · Page 2Linked to original sources
PubMed1994

Conservation of wingless patterning functions in the short-germ embryos of Tribolium castaneum.

During embryogenesis, all insects reach a conserved, or phylotypic, stage at which all future segments are present. Different insects, however, arrive at this stage by overtly different pathways. In the long-germ insect Drosophila melanogaster, segmentation of the entire embryo occurs nearly simultaneously and results from the action of a cascade of transcriptional regulatory factors that operate in the acellular environment of the syncytial blastoderm. In short-germ insects, segmentation occurs in an anterior-to-posterior sequence, within a cellular environment, and might then be dependent on intercellular signalling. To compare the molecular mechanisms of segmentation, we have isolated a homologue of the Drosophila wingless gene, a mediator of cell-cell communications, from the short-germ beetle Tribolium castaneum. The principal features of wingless expression patterns in Drosophila are conserved in Tribolium, including its early deployment in rostral and caudal domains in the blastoderm, its segmental iteration in cells immediately anterior to cells expressing the engrailed gene, and its later restriction to a ventral sector of the developing appendages.

Amino Acid Sequence↗
PubMed1993

Abnormal noradrenergic function in posttraumatic stress disorder.

To evaluate possible abnormal noradrenergic neuronal regulation in patients with posttraumatic stress disorder (PTSD), the behavioral, biochemical, and cardiovascular effects of intravenous yohimbine hydrochloride (0.4 mg/kg) were determined in 18 healthy male subjects and 20 male patients with PTSD. A subgroup of patients with PTSD were observed to experience yohimbine-induced panic attacks (70% [14/20]) and flashbacks (40% [8/20]), and they had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol levels, sitting systolic blood pressure, and heart rate than those in healthy subjects. In addition, in the patients with PTSD, yohimbine induced significant increases in core PTSD symptoms, such as intrusive traumatic thoughts, emotional numbing, and grief. These data were consistent with a large body of preclinical data that indicated that uncontrollable stress produces substantial increases in noradrenergic neuronal function. We discuss the implications of these abnormalities in noradrenergic functional regulation in relation to the long-term neurobiological sequelae of severe uncontrollable stress and the pathophysiological relationship between PTSD and other anxiety disorders, such as panic disorder.

Adult↗
PubMed1993

Trauma-related symptoms in veterans of Operation Desert Storm: a preliminary report.

OBJECTIVE: This study was designed to examine prospectively the development of trauma-related symptoms over time in two reserve units of Operation Desert Storm veterans. METHOD: One month and 6 months after returning from the Persian Gulf area, 84 National Guard reservists, from one medical unit and one military police unit, completed questionnaires on their exposure to combat and to specific stressors and rated the severity of their symptoms of posttraumatic stress disorder (PTSD) on two different scales. Differences in symptom severity at the two time points were analyzed. RESULTS: Scores on the Mississippi Scale for Combat-Related Post-Traumatic Stress Disorder, but not severity ratings on a symptom scale based on DSM-III-R PTSD criteria, increased significantly from the 1-month to the 6-month rating time. At both time points, symptoms of hyperarousal were more severe than symptoms of reexperiencing or avoiding trauma-related events. Level of exposure to combat, as reflected by the Combat Exposure Scale and a Desert Storm trauma questionnaire, was significantly associated with score on the Mississippi PTSD scale. There were no significant differences in combat exposure and PTSD symptoms between the male and female subjects or between the medical and police units. CONCLUSIONS: These preliminary findings suggest that a high percentage of Desert Storm veterans experienced some trauma-related symptoms after returning to the United States. Six months after the war, these symptoms, although relatively mild, had not significantly improved in this study group as a whole. For research on longer-term outcome, follow-up of these 84 reservists continues.

Combat Disorders↗
PubMed1993

Long-term outcome of panic disorder after short-term imipramine and behavioral group treatment: 2.9-year naturalistic follow-up study.

Twenty-eight patients with a DSM-III diagnosis of agoraphobia with panic attacks who completed a 4-month combined drug and behavioral treatment program and who were then discharged on imipramine were interviewed 1 to 5 years after being discharged. At the time of follow-up, half of the patients were medication free, eight were receiving a lower dose of imipramine, two were receiving the same dose as at the time of discharge, and four patients were receiving other antipanic medications. Panic attack frequency remained reduced at the time of follow-up, as did all anxiety and all impairment ratings. These improvements were similar between patients receiving and not receiving imipramine at this time. Long-term outcome was independent of nonpharmacological therapy during the follow-up interval and lifetime diagnosis of major depression at the time of admission. Our data suggest that improvement observed after 4 months of treatment with imipramine and behavioral therapy is maintained after 1 to 5 years, even for many patients who reduced the dose of or discontinued imipramine. Long-term, randomized studies are needed to compare the efficacy of treatments and to determine treatment duration.

Adult↗
PubMed1993

Open prospective trial of fluoxetine for posttraumatic stress disorder.

Twenty-seven patients with combat-related posttraumatic stress disorder (PTSD) entered an open, prospective, 10-week trial of fluoxetine, beginning with 20 mg/day and increasing to 80 mg/day until response was optimal or side effects prohibited dose increase. Nineteen patients completed 3 or more weeks and were included in the data analysis. Total Clinician-Administered PTSD Scale scores decreased from a mean of 64.5 at baseline to 42.7 at endpoint (F = 7.17, p < 0.001), and improvement was significant in each of the three PTSD subscales (reexperiencing, avoidance/numbing, and hyperarousal). Depression and anxiety ratings showed similar improvements, and suicidality ratings did not increase. Global improvement scores decreased from 4.0 at baseline to 2.67 at endpoint (F = 12.08, p < 0.001); however, improvement in social and occupational functioning was minimal. Appreciable improvement tended to occur after 6 weeks, suggesting that higher fluoxetine doses and/or duration than that used for depression may be indicated in this population. Panic attack frequency decreased by at least 50% in six of eight patients who kept panic diaries. The high dropout rate reflects problems with side effects, anxiety symptoms, external events, and substance abuse. Our data suggest that fluoxetine is effective in reducing reexperiencing, avoidance, and hyperarousal symptoms of PTSD, and this improvement is independent of comorbid panic disorder. In addition, fluoxetine appears to be effective in reducing panic attacks in PTSD patients. The efficacy of fluoxetine for some PTSD patients is interesting in light of emerging neuropharmacologic data suggesting serotonergic dysregulation in some PTSD patients. Noradrenergic hypotheses are also discussed. The findings should be confirmed by double-blind, placebo-controlled studies.

Adult↗
PubMed1992

Controlled trial of alprazolam supplementation during imipramine treatment of panic disorder.

To investigate whether alprazolam (ALP) coprescription early in the imipramine (IMI) treatment of panic disorder would improve overall treatment response to IMI alone, 48 panic disorder patients were randomly assigned to receive either IMI plus placebo or IMI plus ALP for 4-6 weeks, followed by 2 weeks of IMI plus placebo-ALP taper and 2 more weeks of IMI alone. Although patients in the IMI plus ALP group improved more quickly, significantly more patients in the IMI plus ALP group could not follow the taper schedule. The results suggest that studies employing other benzodiazepines or other ALP dosage or taper schedules would be required to demonstrate any benefit for the IMI plus early benzodiazepine cotreatment strategy over IMI alone in the routine pharmacologic management of panic disorder.

Adolescent↗
PubMed1992

Noradrenergic neuronal dysregulation in panic disorder: the effects of intravenous yohimbine and clonidine in panic disorder patients.

In order to evaluate possible abnormal noradrenergic neuronal functional regulation in patients with panic disorder, the behavioral, biochemical and cardiovascular effects of intravenous yohimbine (0.4 mg/kg) and clonidine (2 micrograms/kg) were determined in 15 healthy subjects and 38 patients with panic disorder. A subgroup of 24 panic disorder patients were observed to experience yohimbine-induced panic attacks and had larger yohimbine-induced increases in plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) than healthy subjects and other panic disorder patients. A blunted growth hormone response to clonidine and a significant clonidine-induced decrease in plasma MHPG was also observed in this subgroup of panic disorder patients. These data replicate and extend previous investigations, which are consistent with a large body of preclinical and human data relating increased noradrenergic neuronal function to human anxiety and fear states.

Adult↗
PubMed1991

Isolation and embryonic expression of an abdominal-A-like gene from the lepidopteran, Manduca sexta.

Using sequence homology to the Drosophila Antennapedia gene, we isolated a homeobox-containing gene from the lepidopteran, Manduca sexta. Sequence analysis and in situ hybridizations to tissue sections suggest that the Manduca gene encodes a lepidopteran homologue of the Drosophila Bithorax complex gene abdominal-A. The predicted amino acid sequence of a 76 amino acid region that includes the homeobox and the regions immediately flanking it are identical between the Manduca and Drosophila genes. Northern blots reveal that the manduca abd-A gene is expressed first in the early embryo and continues to be expressed throughout later embryonic and larval stages. In situ hybridizations show that the posterior half of the first abdominal segment marks the anterior border of the Manduca abd-A expression. This expression pattern demonstrates the conservation of parasegments as domains of gene activity in the lepidopteran embryo. The Manduca abd-A expression extends from the posterior half of the first abdominal segment through the tenth abdominal segment, a domain that is greater than that of the Drosophila abd-A expression, and reflects the difference in visible segment number between the two insects.

Amino Acid Sequence↗
PubMed1990

Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine.

To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).

Adult↗
PubMed1990

Noradrenergic function in panic disorder.

There is neuroanatomical, neurochemical, neurophysiologic, and behavioral preclinical evidence that suggests that the development of anxiety or fear relates, in part, to increased brain noradrenergic neuronal activity. In laboratory animals, uncontrollable stress has been shown to be associated with increases and altered regulation of brain noradrenergic function. Pharmacologic or electrical activation of noradrenergic neurons of the major brain noradrenergic nucleus, the locus ceruleus (LC), has anxiogenic effects in nonhuman primates. Elevated LC neuron firing is associated with anxiety or fear responses in freely moving cats. These observations are supported by clinical investigations that have demonstrated abnormal noradrenergic system regulation in panic disorder patients. From a neurodevelopmental perspective, these findings may be related to the natural course of panic disorder.

Animals↗
PubMed1989

Clinical and medication outcome after short-term alprazolam and behavioral group treatment in panic disorder. 2.5 year naturalistic follow-up study.

Sixty patients with agoraphobia with panic attacks or panic disorder who completed a 4-month combined drug and behavioral group treatment program and were discharged on a regimen of alprazolam were interviewed 1.7 to 4 years (mean, 2.5 years) after discharge. At follow-up (FU), 18 (30%) of the patients had discontinued alprazolam treatment, 36 (60%) continued with a lower dose, 3 (5%) received the same dose, and 3 (5%) received an increased dose compared with discharge. A lower frequency of panic attacks at admission was associated with an increased ability to discontinue alprazolam treatment. There was little evidence of tolerance to the antipanic effects of alprazolam. Panic attack frequency dropped from a mean of 4.4 attacks per week at admission to 1.2 attacks per week at discharge and remained decreased at 1.6 attacks per week at FU. Treatment gains in the program were maintained or enhanced on 11 of 14 behavioral measures at FU and were similar in the groups that were receiving and not receiving alprazolam. Patients receiving nonpharmacologic therapy in the FU period tended to have greater symptom severity, possibly due to self-selection. A lifetime diagnosis of major depression at admission was associated with higher levels of depressive and anxiety symptoms and higher alprazolam doses at FU. Episodes of major depression were common in the FU period and did not appear to be prevented by initial alprazolam and behavioral therapy or by low-dose alprazolam maintenance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗