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Biomedical subjects

J A Jesberger

Publications and source records attributed to J A Jesberger.

At least 19 recordsLinked to original sources

Thermal lesion conspicuity following interstitial radiofrequency thermal tumor ablation in humans: a comparison of STIR, turbo spin-echo T2-weighted, and contrast-enhanced T1-weighted MR images at 0.2 T.

The purpose of this study was to compare the contrast between radiofrequency (RF) thermal liver lesions and surrounding tissue in T2-weighted turbo spin-echo sequences (TSE T2), short TI inversion recovery techniques (STIR), and contrast-enhanced (CE) T1-weighted spin-echo images. Nineteen RF thermal ablations were performed on eight patients with metastatic liver tumors. After ablation, contrast-to-noise ratios (CNRs) were calculated between mean signal amplitudes from three regions of interest (ROI) (lesion, surrounding edema, and normal tissue) using TSE T2-weighted, STIR, and contrast-enhanced T1-weighted (CE T1) sequences for each lesion. CNRs between the thermal lesion and normal liver tissue for both TSE T2-weighted (mean 0.9) and STIR (2.0) images were significantly lower than for CE T1-weighted (8.4) images (t-test, alpha = 0.05). However, CNRs between edema rim and the core of the thermal lesion for both TSE T2-weighted (8.1) and STIR images (7.2) were not significantly different (t-test, alpha = 0.05) from CNRs between lesion and normal tissue for CE T1-weighted images (8.4), nor was the CNR between edema rim and normal tissue for both TSE T2-weighted (10.3) and STIR (9.8) images. Although the edema was not visible on CE T1-weighted images, 18 of 19 lesions (94.7%) were surrounded by a hyperintense rim on TSE T2-weighted or STIR images. Both TSE T2-weighted and STIR sequences represent valid techniques for repeatable assessment of RF thermal lesions.

Adult↗

Olanzapine safety and efficacy in patients with borderline personality disorder and comorbid dysthymia.

BACKGROUND: Numerous medications have been tested in patients with borderline personality disorder (BPD) and/or schizotypal personality disorder (SPD). Although many of the medications tested have been demonstrated to be useful, no clear main treatment for BPD has emerged. Despite the efficacy of some of the medicines, acceptability and side effects have proven to be barriers to the use of medication. Therefore, an open-label olanzapine trial utilizing objective ratings was performed. METHODS: Patients suffering from BPD and dysthymia were included in an 8-week, open-label study of olanzapine monotherapy. The first 4 weeks of the trial allowed for flexible dosing; during the last 4 weeks, olanzapine dose was held constant. Patients were rated on Hopkins Symptoms Checklist 90 (SCL-90), Brief Psychiatric Rating Scale (BPRS), Global Assessment of Function (GAF), Barratt Impulsivity Scale (BIS 11), and Buss-Durkee Hostility Inventory (BDHI). RESULTS: Eleven patients completed at least 2 weeks; nine of the patients finished the entire trial. There was a robust and statistically significant reduction in the five global ratings. Within the global ratings, symptoms of psychoticism, depression, interpersonal sensitivity, and anger were among the symptoms to be reduced. No movement disorder symptoms were noted for any of the patients. CONCLUSIONS: In this open-label pilot study, patients treated with olanzapine showed statistically significant reduction in self-rated and clinician-rated scales. Symptoms associated with BPD and dysthymia were among those to be substantially reduced. Further studies to explore olanzapine's efficacy versus placebo, as well as comparison to other potential treatments for BPD, are important next steps.

Adult↗

An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects.

BACKGROUND: There are few imaging studies in adolescent patients with either schizophrenia or bipolar disorder. Such studies are of interest because adolescents may have a more severe illness and neurodevelopmental events may have a greater role in their pathophysiology. METHODS: We compared 20 patients with schizophrenia and 15 patients with bipolar disorder (10 to 18 years) to 16 normal adolescents on magnetic resonance imaging (MRI) measures of intracranial volume and ventricular and sulcal enlargement. Two planned comparison contrasts were employed, one comparing the two patient groups to each other (contrast 1), and one comparing both patient groups combined to control subjects (contrast 2). RESULTS: None of the contrast 1 comparisons (schizophrenia vs bipolar) were statistically significant. Contrast 2 comparisons (control subjects vs patients) were statistically significant for intracranial volume (reduced in patients) as well as frontal and temporal sulcal size (increased in patients). CONCLUSIONS: The patient groups were not statistically significantly different from each other on any measure. The combined patient groups were different from control subjects on intracranial volume and frontal and temporal sulcal size. Also, there was evidence for ventricular enlargement, after removal of a control subject with an extreme value. These findings indicate that the same abnormalities noted in adult populations are present in adolescents.

Adolescent↗

Assessment of dysphagia with the use of pulse oximetry.

Recent anecdotal literature has shown a relation between arterial oxygen saturation (SpO2), as measured by pulse oximetry, and aspiration during eating. The present study was designed to determine whether bedside pulse oximetry has a role in the assessment of pharyngeal phase dysphagia. Forty-six adult patients with clinically suspected swallowing abnormalities underwent modified barium swallow to evaluate dysphagia. After determining baseline oxygen saturation by pulse oximetry, different consistencies of barium were sequentially ingested. Patients were monitored for radiographic evidence of penetration or aspiration, which was correlated with continuous SpO2 recording. Patients who exhibited aspiration or penetration without clearing had a significant decline in SpO2 compared with those patients who penetrated but cleared or in whom no penetration was observed. These relations were not associated with age, gender, or diagnosis. These preliminary data indicate that bedside pulse oximetry may be a useful tool in the evaluation of patients with dysphagia.

Adult↗

Brain activation during silent word generation evaluated with functional MRI.

This is a study of word generation during functional MRI (fMRI). Eleven normal healthy subjects were instructed to generate words covertly, (i.e., silently) that began with particular letters. Images were acquired on a conventional 1.5T scanner at three contiguous axial planes encompassing language-related areas of the temporal and frontal lobe. The data were analyzed at the level of a Talairach box, after individually fitting the proportional Talairach grid system to each slice. The main variable of interest was the number of activated pixels within a Talairach box. Boxes with a significant increase in the proportion of activated pixels were located in three regions of the left neocortex: (1) Brodmann areas 44 and 45 in the dorsolateral frontal cortex (Broca's area), (2) areas 21 and 37 in the temporal cortex, (3) and the striate/extrastriate cortex (areas 17 & 18). The results are discussed in terms of a cognitive model of word generation and are compared, in detail, with the results of prior relevant imaging studies.

Adolescent↗

The relationship between smooth pursuit performance, motion perception and sustained visual attention in patients with schizophrenia and normal controls.

BACKGROUND: In this study, we tested the hypothesis that low smooth pursuit gain in schizophrenia is related to an abnormality in motion perception. METHODS: The subjects were 19 schizophrenics treated with clozapine and 19 controls. In addition to smooth pursuit and motion perception paradigms, sustained attention was also assessed using a continuous performance task (CPT). RESULTS: In the patient group, there was a statistically significant negative correlation between smooth pursuit gain and motion perception threshold (r = -0.60, P < 0.01). This relationship was not secondary to attention deficits as assessed by the CPT. CONCLUSIONS: Our results are consistent with the notion that the smooth pursuit gain deficit is related to a deficit in motion perception rather than in attention. Brain area V5 (also referred to as "MT' in macaque), located in the parieto-occipital region, is known to be critically important both for motion perception and gain. Thus, our results point to an abnormality in this area in schizophrenia.

Adult↗

Cognitive impairment in adolescents with schizophrenia.

OBJECTIVE: The purpose of this study was to determine whether adolescent schizophrenia is characterized by neuropsychological deficits. METHOD: The performance on a battery of neuropsychological tests of 17 adolescents with schizophrenia (mean age = 15.71 years) was compared with that of 17 normal adolescents (mean age = 15.12 years). RESULTS: Compared with the normal subjects, the patients were impaired on 10 of the 13 measures; larger effect sizes were shown for measures involving working memory and attention than for those involving secondary memory, generative naming, and executive functions. CONCLUSIONS: Adolescents with schizophrenia have generalized cognitive dysfunction, which is most apparent on tests of attention and working memory.

Adolescent↗

Relationship between smooth pursuit eye-tracking and cognitive performance in schizophrenia.

The relationship between measures of smooth pursuit and neuropsychological performance was assessed in 20 unmedicated schizophrenics. Eye-tracking measures included gain, catch-up saccade parameters, and rate of saccadic intrusions. Neuropsychological measures included tests generally considered as "frontal": Wisconsin Card Sorting Test (WCST), Consonant Trigram Test (CTT), and Controlled Oral Word Association Test (COWAT). The Digit Symbol Test (DST), which is generally considered to be a measure of global functioning, was also included. Gain and other pursuit measures were significantly correlated with the DST and the COWAT, but were not correlated with the WCST or the CTT.

Adult↗

Smooth pursuit performance in patients with affective disorders or schizophrenia and normal controls: analysis with specific oculomotor measures, RMS error and qualitative ratings.

Smooth pursuit performance in schizophrenia and affective disorders has generally been found to be abnormal using a variety of measures. The purpose of this study was to assess patients with these disorders and normal controls in order to compare the different measures across diagnoses. Smooth pursuit was assessed using quantitative specific measures (gain, catch-up saccade rate and amplitude, square-wave jerk rate, number of anticipatory saccades and total time scored), as well as two global measures: root mean-square error (RMS) and qualitative rating. As previously reported, patients with schizophrenia had low gain, increased catch-up saccade rate and spent less time engaged in scoreable smooth pursuit than normal controls. Patients with affective disorders were not statistically different from controls on any of these measures, and had significantly higher gain than patients with schizophrenia. RMS error and qualitative rating measures were highly correlated (r = 0.87). In linear regression analyses, the quantitative specific measures were highly significant predictors of both RMS error and qualitative ratings (P < 0.0001). Linear regression analyses and a modelling study indicated that one quantitative specific measure, the percent of time engaged in scoreable smooth pursuit (total time scored), was most related to global ratings. However, RMS error and qualitative ratings were less sensitive than total time scored to the difference between controls and patients with schizophrenia. These data indicate two smooth pursuit performance deficits in schizophrenia: patients spend less time engaged in scoreable smooth pursuit and have low gain (accompanied by increased compensatory saccades) when the smooth pursuit is engaged.

Adult↗

The effect of apomorphine, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) and placebo on smooth pursuit gain and corrective saccades in normal subjects.

The effects of apomorphine (0.01 mg/kg SC) a direct-acting dopamine (DA) agonist, MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine) (20 mg PO), a direct-acting serotonin (5-HT) agonist, and placebo on smooth pursuit eye movements were evaluated in 10 to 12 normal volunteers. Smooth pursuit was tested just prior to administration of either apomorphine, MK-212, or placebo (on separate days), and then repeatedly tested at 30 min intervals for two hours after dose administration. The smooth pursuit targets were a series of predictable, constant velocity ramps with velocities of 5 degrees/sec (slow target) and 20 degrees/sec (fast target). Eye movements were recorded with infrared oculography, and the following six measures were obtained; steady-state gain (slow-target-gain; fast-target-gain), corrective catch-up saccade (CUS) rate (slow-target-CUS-rate; fast-target-CUS-rate), and CUS amplitude (slow-target-CUS-amplitude; fast-target-CUS-amplitude). The placebo test yielded a statistically significant monotonic decrease over time in slow-target-gain and corresponding increase in slow-target-CUS-rate, but no effects of placebo were noted for the fast target. Apomorphine injection produced a marked reduction in both slow-target-gain and fast-target-gain at 30 min, returning to baseline thereafter. Apomorphine injection also produced a statistically significant increase in slow-target-CUS-amplitude. Ingestion of MK-212 produced a statistically significant increase in slow-target-gain and fast-target-gain as well as a corresponding decrease in slow-target-CUS-rate and fast-target-CUS-rate at 90 min or 120 min. There was evidence that the decline in slow-target-gain after apomorphine was associated with side-effects such as sleepiness, but the decline in fast-target-gain was not related to side-effects. The improved smooth pursuit performance after MK-212 was not related to side-effects. The data suggest that serotoninergic stimulation can improve smooth pursuit performance, whereas dopaminergic stimulation worsens this performance.

Adult↗

Saccadic intrusions into smooth pursuit in patients with schizophrenia or affective disorder and normal controls.

Two types of saccadic intrusions into smooth pursuit eye tracking, anticipatory saccades (AS), and square wave jerks (SWJ), were measured in 23 patients with schizophrenia, 16 patients with affective disorder, and 21 normal controls. Constant velocity (5 degrees and 20 degrees/sec) predictable targets were employed. High resolution infrared oculography was employed to record eye movements. Although most subjects had at least one SWJ, there were no significant group differences, and the highest individual rates of SWJ were seen in the normal control group. On the other hand, AS were never seen in normals, but were present in 25%-44% of patients with either schizophrenia or affective disorder. Both patient groups had significantly more AS than controls, but the two patient groups were not significantly different.

Adult↗

Effect of typical antipsychotic medications and clozapine on smooth pursuit performance in patients with schizophrenia.

The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye movements was tested in 13 patients with schizophrenia or schizoaffective disorder with a repeated measures design. Nineteen normal control subjects were also studied. Compared with controls, patients in the unmedicated state had low smooth pursuit gain, had a higher rate of corrective catch-up saccades, and tended to spend less time engaged in the tracking task. The patients did not significantly differ from controls on catch-up saccade amplitude, square wave jerk rate, or anticipatory saccade rate. Medication with clozapine, but not typical neuroleptics, was associated with an increase in median catch-up saccade amplitude. Number of days on clozapine and clozapine dose both correlated significantly with a worsening of oculomotor performance. No effect of medication with typical neuroleptics was found, although there was some evidence suggesting that such an affect may occur after more prolonged treatment.

Adult↗

Catch-up saccade amplitude is related to square wave jerk rate.

Mean catch-up saccade (CUS) amplitude and square wave jerk (SWJ) rate during pursuit were recorded in 20 normal controls, 23 patients with schizophrenia, and 15 patients with affective disorder, using infrared oculography. Target speed during pursuit was 5 degrees/sec. An especially robust correlation was noted in normal controls between SWJ rate during pursuit and mean CUS amplitude (Spearman's rs = 0.87, P less than 0.0001). This correlation also was present in the psychiatric patients (rs = 0.53, P = 0.0006), although it was significantly weaker than in normal controls (P less than 0.02). There were no significant differences between the patient groups regarding the strength of the relationship. Furthermore, similar strong correlations between SWJ rate during fixation and mean CUS amplitude also were found for normals (rs = 0.73, P = .0002) and both patient groups combined (rs = 0.52, P = 0.0009). The results suggest that saccadic intrusions during tracking tax the saccade correcting system, delaying correction for the position error that accumulates when gain is less than 1.0.

Adult↗

A model of smooth pursuit performance illustrates the relationship between gain, catch-up saccade rate, and catch-up saccade amplitude in normal controls and patients with schizophrenia.

Smooth pursuit eye-tracking performance of 37 unmedicated patients with schizophrenia and 45 normal controls was recorded with infrared oculography, and digitized for off-line analysis of gain and other measures. Target velocity was 5 degrees/sec. Patients with schizophrenia had significantly lower gain than normal controls, confirming several earlier reports. During low gain smooth pursuit tracking, when eye velocity is slower than target velocity, the saccadic system corrects for the accumulating position error with catch-up saccades (CUS). The rate of CUS and the median CUS amplitude were compared between groups. Patients had significantly more CUS than controls, but the median CUS amplitudes were not significantly different. A nonlinear mathematical model of the relationship between gain, CUS amplitude, and CUS rate during steady-state constant velocity tracking was developed to integrate these findings. According to this model, for a given gain, correction for position error can result from either a few large CUS or many small CUS. The fit of the model to empirical data, as assessed graphically and with linear and nonlinear regression techniques, was excellent. The model fit the data for both patients and controls. The psychiatric eye-tracking literature is discussed from the perspective suggested by the modeled relationship.

Adult↗

Oxygen free radicals and brain dysfunction.

Oxygen free radicals, any chemical moiety containing an oxygen atom with an unpaired electron in the outer orbital shell, are generated during many normal biochemical reactions in living tissue. The unpaired electron makes these compounds highly reactive and they can initiate disruptive peroxidation reactions with various substrates important to the survival of cells such as proteins, lipids and nucleic acids. A fairly complex defense system has evolved to protect living tissue from free radicals and to minimize the damage they might cause. Neurons are especially vulnerable to free radical attack and impaired defenses or exposure to excess free radicals can lead to neuronal death. Free radicals contribute to neuronal loss in cerebral ischemia and hemorrhage and may be involved in the degeneration of neurons in epilepsy, schizophrenia, tardive dyskinesia, normal aging, Parkinson's Disease and Alzheimer's Disease. The development of drugs that limit or prevent the attack of free radicals on neurons would be an important advance in the treatment of these conditions.

Animals↗

Brain output dysregulation induced by olfactory bulbectomy: an approximation in the rat of major depressive disorder in humans?

Mounting evidence indicates that the emotional, cognitive, neurovegetative and behavioral symptoms of patients with major depressive disorder are due to abnormal neurochemical substrates in the brain. Although the specific neurochemical abnormalities responsible have not been identified, the presenting symptoms of major depression are consistent with a disruption of normal neural communications between the limbic system and hypothalamus. Following removal of the olfactory bulbs, rats display a syndrome of behavioral deficits that also reflect a disruption of the limbic-hypothalamic axis. Moreover, the bulbectomy induced deficits are selectively reduced by the chronic administration of the same drugs that alleviate the symptoms of depression when given chronically to the patients. In addition to this pharmacological similarity, there are also numerous behavioral parallels between bulbectomized rats and major depression patients. The bulbectomized rat provides a good model in which to study antidepressant drugs and also may provide neurochemical and neuroanatomical data that are relevant to understanding the biological substrates of emotion and the causes of depression in humans.

Animals↗

Differential effects of antidepressant drugs on [3H]dihydroalprenolol and [3H]imipramine ligand recognition sites in olfactory bulbectomized and sham-lesioned rats.

In the olfactory bulbectomy rat model of major depression, the binding of [3H]imipramine is increased by 60% in the midbrain, reduced by 30% in the pons and by 20% in the hippocampus, and unchanged in the hypothalamus 6 weeks after the bulbectomy. Binding of [3H]dihydroalprenolol is unchanged in the midbrain but is increased by 30% in the pons and 15% in the hippocampus. The i.p. administration of the antidepressants amitriptyline, mianserin, tranylcypromine (all at a dose of 10 mg/kg) or iprindole (25 mg/kg) for 28 days followed by a 5-day drug washout period, alters brain part [3H]imipramine and [3H]dihydroalprenolol binding in a manner that is a function of the particular drug, brain part and lesion effect. Only in the hippocampus did the lesion increase beta-binding that was reduced by all four antidepressant drugs.

Amitriptyline↗

Effects of antidepressant drugs on the behavior of olfactory bulbectomized and sham-operated rats.

Removal of the main olfactory bulbs in rats has been shown to alter neuronal function in brain areas involved in emotional regulation and homeostasis. These neuronal alterations result in maladaptive behavioral patterns and elevated plasma corticosterone that are suggestive of the symptom profile of patients with primary unipolar depression. Moreover, the endocrine and behavioral deficits of bulbectomized rats are reversed by the chronic administration of drugs that reverse the symptoms of depression in people when given chronically. However, the therapeutic improvements seen in patients with depression are not directly due to molecules of the antidepressant drug but rather to some relatively long-lasting compensatory change induced in the neuronal substrate by the drug. The present research demonstrates that the reversal of the olfactory bulb lesion deficits following chronic antidepressant drug administration in rats is not due to molecules of the drug per se but rather to some drug-induced change in the neuronal substrate that continues for at least 5 days after the last dose of drug. These endocrine, behavioral, and pharmacological similarities suggest that the study of rats with olfactory bulb ablation may make significant contributions to the understanding of the neuroscience of primary unipolar depression in humans.

11-Hydroxycorticosteroids↗