Search PubMed⌕ Search

Biomedical subjects

I K Lyoo

Publications and source records attributed to I K Lyoo.

12 recordsLinked to original sources
PubMed2006

Magnetic resonance spectroscopy for measuring the biodistribution and in situ in vivo pharmacokinetics of fluorinated compounds: validation using an investigation of liver and heart disposition of tecastemizole.

BACKGROUND AND OBJECTIVE: The study of biodistribution and in situ pharmacokinetics is a challenging, but sometimes very important, aspect of premarketing characterization of drugs. We aimed to develop a non-invasive fluorine magnetic resonance (MR) spectroscopic method for the absolute quantitation of a mono-fluorinated compound and of its metabolites in the heart and liver of healthy subjects for this purpose. METHOD: We used fluorine MR spectroscopy (MRS) at 4 T (Tesla) and external standardization in an open label multiple-dose study. Twenty-three healthy adult subjects were enrolled in the study. The surface coil localized fluorine MR spectrum was monitored in the heart and liver at baseline and after oral administration of multiple doses of tecastemizole. Steady-state measurements were made at set time points that depended upon dose, and washout measurements were made only on subjects in which in vivo fluorine signal was observed. RESULTS AND DISCUSSION: At 4 T, under the given experimental conditions, the method had a lower limit of quantitation (LLOQ) of about 2.6 microm and a limit of detection (LOD) of about 0.3 microm for solution state samples (linewidth approximately 15 Hz). The measurement reproducibility was 6.4% using a 50 microm phantom. The effect of MR operator and spectral analyst on the calculated calibration curve slope was small, with inter-rater correlation coefficients of 0.999 and 0.998 respectively. MR signal from fluorine-containing tecastemizole-related moieties was observed in situ only at day 8 in the liver of three of five subjects dosed at 270 mg/day. The average in situ concentration was estimated to be 58+/-22 microm, with an average test-retest reproducibility of 216%. Extrapolating the in vitro results to human measurements, with an approximate linewidth of 250 Hz, predicts in situ LOD and LLOQ values of approximately 6 and 44 microm respectively. However, the human study had a fluorine MRS LOD of approximately 20 microm. The decrease in sensitivity and the increase in variability of the in vivo, in situ measurements compared with the validation study most likely arose from coil placement and incomplete rephasing of the MR signal by the respiratory phase compensation method. CONCLUSION: The measured concentrations were the lowest ever recorded for a multi-dose exogenous mono-fluorinated compound in the human liver using a validated fluorine MR quantitation method. The proposed non-invasive MR method for studying the biodistribution and in situ pharmacokinetics of mono-fluorinated compounds in the liver and heart should have broader application to the development of non-invasive biomarkers.

Adult↗
PubMed2003

Patterns of changes in temperament and character inventory scales in subjects with obsessive-compulsive disorder following a 4-month treatment.

OBJECTIVE: The purpose of this study was to assess changes in the temperament and character patterns in subjects with obsessive-compulsive disorder (OCD) following the treatment for obsessive/compulsive and accompanying depressive symptoms. METHOD: Study subjects were 35 patients who met the DSM-IV criteria for OCD. All subjects were assessed with the Temperament and Character Inventory (TCI), the Yale-Brown Obsessive-Compulsive Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory before and after a 4-month treatment. RESULTS: Harm Avoidance (HA) scores in OCD subjects before treatment significantly decreased after treatment. However, the Self-Directedness scores, which were significantly lower than healthy comparison subjects before treatment, did not change. In addition, Reward Dependence scores in OCD subjects, which were not significantly different from healthy comparison subjects before treatment, significantly increased after treatment. CONCLUSION: The TCI pattern of untreated OCD subjects (high HA and low Self-Directedness, relative to healthy comparison subjects) and the decrease of HA scores and no change in Self-Directedness scores following a successful treatment suggest that temperaments are more amenable to treatment than characters.

Adolescent↗
PubMed2001

Patterns of temperament and character in subjects with obsessive-compulsive disorder.

BACKGROUND: The purpose of this study was to assess the temperament and character patterns of obsessive-compulsive disorder (OCD) patients and to investigate the relationship between patterns of temperament and character and the severity of obsessive-compulsive symptoms. METHOD: The subjects were 40 patients who met DSM-IV criteria for OCD and 40 age-, sex-, and IQ-matched healthy controls. All subjects completed Cloninger's Temperament and Character Inventory. Other instruments included the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory. RESULTS: OCD patients showed significantly higher scores of harm avoidance and lower scores of novelty seeking and self-directedness compared with healthy comparison subjects. In addition, the high harm avoidance and low self-directedness scores are correlated with a greater severity of obsessive-compulsive symptoms in OCD subjects (multiple regression analysis, beta = 0.39, t = 2.54, df = 34, p = .016; beta = -0.41, t = 2.46, df = 34, p = .019, respectively). CONCLUSION: OCD patients had distinct patterns of temperament and character compared with healthy comparison subjects. In addition, these patterns are specifically related to the severity of obsessive-compulsive symptoms.

Adult↗
PubMed2000

Three-year follow-up of women with the sole diagnosis of depressive personality disorder: subsequent development of dysthymia and major depression.

OBJECTIVE: The authors sought to determine whether subjects with the sole diagnosis of depressive personality disorder are at higher risk for developing dysthymia and major depression than are healthy comparison subjects. METHOD: Eighty-five women with depressive personality disorder who had no comorbid axis I or axis II disorders and 85 age-matched healthy comparison women were initially recruited and reinterviewed 3 years later to evaluate the cumulative incidence rate of dysthymia and major depression. RESULTS: At the 3-year follow-up assessment, the women with depressive personality disorder had a significantly greater odds ratio for developing dysthymia than did the healthy comparison women. The difference in odds ratios for the development of major depression between women with and without depressive personality disorder did not reach statistical significance. CONCLUSIONS: The present study, the first to determine the subsequent development of dysthymia and major depression in subjects with the sole diagnosis of depressive personality disorder, found that subjects with depressive personality disorder had a greater risk of developing dysthymia than did healthy comparison subjects at 3-year follow-up. Findings of the current study also suggest that depressive personality disorder may mediate the effects of a family history of axis I unipolar mood disorders.

Adult↗
PubMed1998

A brain MRI study in subjects with borderline personality disorder.

BACKGROUND: There have been only a few brain computed tomography imaging studies, with mostly negative findings, in subjects with borderline personality disorder (BPD). This is the first MRI study which evaluated the structural abnormalities of the brain in subjects with the sole diagnosis of BPD. METHODS: Twenty-five subjects with BPD were compared with age-, gender-matched healthy comparison subjects (n=25) on volumes of the frontal lobes, the temporal lobes, the lateral ventricles, and the cerebral hemispheres in brain magnetic resonance imaging. RESULTS: Subjects with BPD had a significantly smaller frontal lobe compared to comparison subjects (multivariate regression analysis, t=2.225, df=46, P=0.031). There were no significant differences in volumes of the temporal lobes, the lateral ventricles, and the cerebral hemispheres between subjects with and without BPD. LIMITATIONS: Strict inclusion and exclusion criteria employed in the present study may make it difficult to generalize our findings. The gray matter and white matter of the brain were not measured separately. Differences in head tilt during image acquisition were not corrected. CONCLUSIONS: The current study reports a smaller frontal lobe volume on brain MRI in subjects with BPD compared with healthy comparison subjects. This finding may serve as a potentially useful biological variable that may allow for subtyping BPD.

Adolescent↗
PubMed1998

Reliability and validity of depressive personality disorder.

OBJECTIVE: Depressive personality disorder was introduced into DSM-IV's appendix amid controversy. While that disorder appears to be a reliable and valid one, the authors offer new data about its relationship to major depression, dysthymic disorder, and other personality disorders. METHOD: The authors assessed 54 subjects with early-onset, long-standing mild depressive features for depressive personality disorder, axis I and axis II disorders, family history, and treatment history; they conducted follow-up interviews 1 year after the baseline assessment. Subjects with (N=30) and without (N=24) depressive personality disorder were characterized and compared in terms of those variables. RESULTS: Although depressive personality disorder and dysthymia co-occurred in some subjects, 63% of subjects with depressive personality disorder did not have dysthymia, and 60% did not have current major depression. Although subjects with depressive personality disorder were more likely than the mood disorder comparison group to have another personality disorder, 40% had no such disorder. Contrary to study hypotheses, mood disorder was not more common in first-degree relatives of subjects with depressive personality disorder than in relatives of the comparison group. Subjects with and without depressive personality disorder had similar rates of past treatment with medication and psychotherapy; however, the duration of psychotherapy was significantly longer for subjects with than for those without depressive personality. The depressive personality diagnosis was relatively stable over the 1-year follow-up period. CONCLUSIONS: Depressive personality disorder appears to be a relatively stable condition with incomplete overlap with axis I mood disorders and personality disorders. Further studies are needed to better characterize its treatment response and relationship to axis I mood disorders.

Adult↗
PubMed1997

Regional atrophy of the corpus callosum in subjects with Alzheimer's disease and multi-infarct dementia.

Regional areas of the corpus callosum (CC) were evaluated in subjects with dementia. The area of the CC and seven distinct subdivisions were measured in subjects with Alzheimer's disease (AD) (n = 162), multi-infarct dementia (MID) (n = 28), and in a healthy comparison group (n = 36). There were significant differences in the regional areas of the CC for both the AD and MID patients relative to values for the comparison subjects. When mildly demented (MMSE > or = 21), subjects with AD had significantly smaller posterior midbody, isthmus, and splenium and subjects with MID had significantly smaller genu relative to comparison subjects. This study reports different patterns of regional CC area loss in subjects with AD and MID.

Aged↗
PubMed1996

Structural abnormalities in brain magnetic resonance images of depressed children.

OBJECTIVE: Brain magnetic resonance images (MRIs) of 65 children and adolescents who were hospitalized with depressive disorders (DD) were compared with the brain MRIs of 18 hospitalized psychiatric controls (PC) without a depressive disorder. METHOD: Volumetric analyses were used to measure frontal lobe volumes (FLV), lateral ventricular volumes (VV), and total cerebral volumes (CV) for all subjects. To correct for differences in absolute cerebral volume associated with different body and head size, the ratios of FLV/CV and VV/CV were used to compare differences between the two groups. A multivariate analysis was used to control for the effects of several independent variables (age, sex, diagnosis). RESULTS: Significant differences were seen in the FLV/CV ratio and the VV/CV ratio when the results were compared between the two groups (DD versus PC). The DD group had a significantly smaller FLV/CV ratio (t = 2.148, df = 79, p = .035) and a significantly larger VV/CV ratio (t = -2.093, df = 79, p = .040). CONCLUSION: The findings are consistent with previous reports in depressed adults and may implicate the frontal lobes in the pathogenesis of early-onset depressive disorders.

Adolescent↗
PubMed1996

Unsuspected multiple sclerosis in patients with psychiatric disorders: a magnetic resonance imaging study.

Over a 6-year period, 2,783 subjects, consecutively referred from the inpatient unit of a private psychiatric hospital, were evaluated with brain MRI. Twenty-three patients (0.83%) had brain white matter hyperintensities (WMH) that were highly suggestive of multiple sclerosis (MS). The subjects with WMH consistent with MS were most commonly diagnosed with affective illness. They had a significantly longer length of hospital stay during the index admission, a greater number of past psychiatric admissions, a greater prevalence of brain atrophy, and a history of more frequent neurological symptoms and signs than those without these findings.

Adolescent↗
PubMedDate not supplied

Family problems and relationships for adults with borderline personality disorder.

The purpose of this study was to compare the perceptions of the family in patients with borderline personality disorder (BPD) to the perceptions of their parents and to those of normative families. We compared ratings on measures of family problems, environment, and relationships from a sample of 21 patients with BPD to ratings by their parents and to standardized ratings from normative families. The results were that (1) patients with BPD perceived their family environment and relationships significantly more negatively than did their parents or the normative families, and (2) parents of a patient with BPD agreed more with each other than with their offspring, with both parents often close to normative standards. We conclude that defensive reactions at the time of initial evaluation probably account for the frequently cited schism between BPD patients' particularly negative reports of their families and the more normative reports by their parents. Clinicians should obtain parental viewpoints as an essential part of evaluating the family environment.

Adolescent↗