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Biomedical subjects

Gopalan Sethuraman

Publications and source records attributed to Gopalan Sethuraman.

At least 19 recordsLinked to original sources
PubMed2006

Characteristics of two alternative schizophrenia remission definitions: relationship to clinical and quality of life outcomes.

BACKGROUND: The goal of these secondary analyses of clinical trial data was to characterize clinical outcomes in patients with schizophrenia who met symptom severity or duration thresholds for two alternative definitions of remission, and to explore their relationships to improvement duration and quality of life outcomes. METHODS: Definition 1 used threshold criteria for selected PANSS items sustained over at least 6-months Definition 2 used Brief Psychiatric Rating Scale (BPRS) % change, a threshold score for the Clinical Global Improvement-Severity (CGI-S) maintained for at least 8 weeks, and threshold scores for selected BPRS items. Positive and Negative Symptom Scale (PANSS) and Quality of Life scale (QLS) total scores were pooled from 6 clinical trials. The extent to which the alternative severity thresholds from these two definitions and duration of clinical improvement were associated with different clinical and QLS outcomes was explored. Regression analysis also assessed the relative contribution of each of the components of the two definition severity thresholds to improvements in QLS Total score. RESULTS: Increases in QLS scores were greater for those patients who met either threshold criteria relative to those who met neither (p<.0001). Significantly greater improvements in QLS scores were observed for patients who met either threshold criteria at the 8-, 16- and 24-week visits relative to those who met criteria at weeks 16 and 24, or at week 24 only (p<0.001), as well as for the subset of patients who met threshold criteria at both 24 and 52 weeks relative to those who met criteria at only one of these 2 time points. Only 31% to 47% of patients meeting threshold criteria for either definition at the 8-, 16- or 24-week visits remained in remission at the 52-week visit. Among the severity threshold components analyzed, BPRS total % change from baseline was the strongest predictor of improvement in QLS scores. CONCLUSIONS: Quality of life improved most for patients who achieved severity thresholds associated with either remission criteria and who stayed improved for longer periods. Total BPRS change scores accounted for the greatest percentage of the QLS scores variance. Only a fraction of patients who meet severity criteria for either remission definition early in treatment will remain at that level of improvement within the subsequent 9-12 months.

Adolescent↗
PubMed2006

Rapamycin causes regression of astrocytomas in tuberous sclerosis complex.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs. Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro. We sought to see whether therapy with oral rapamycin could affect growth or induce regression in astrocytomas associated with TSC. METHODS: Five subjects with clinically definite TSC and either subependymal giant cell astrocytomas (n = 4) or a pilocytic astrocytoma (n = 1) were treated with oral rapamycin at standard immunosuppressive doses (serum levels 5-15 ng/ml) from 2.5 to 20 months. All lesions demonstrated growth on serial neuroimaging studies. Magnetic resonance imaging scans were performed before and at regular intervals following initiation of therapy. RESULTS: All lesions exhibited regression and, in one case, necrosis. Interruption of therapy resulted in regrowth of subependymal giant cell astrocytomas in one patient. Resumption of therapy resulted in further regression. Treatment was well tolerated. INTERPRETATION: Oral rapamycin therapy can induce regression of astrocytomas associated with TSC and may offer an alternative to operative therapy of these lesions.

Adolescent↗
PubMed2006

Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment?

This secondary report from our 52-week, double-blind, relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment. On average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 +/- 10.6 points during treatment with olanzapine (10-20 mg/d; n = 212), but decreased by 7.1 +/- 14.6 points during treatment with placebo (n = 92; P < 0.001). Mean Quality-of-Life Scale total scores worsened in both treatment groups for the relapsing patient subgroup, whereas for nonrelapsing patients, those treated with olanzapine had significantly improved mean Quality-of-Life Scale total scores compared with those given placebo. For a subset of nonrelapsing patients who were considered "nonexacerbating" on the basis of minimal non-clinically relevant increases in psychopathology, Quality-of-Life Scale total mean change was no better (P = 0.066) for those given placebo (2.7 +/- 11.0; n = 40) than those treated with olanzapine (5.7 +/- 8.9; n = 174). Path analysis indicated a direct effect of treatment (approximately 29%) on quality of life that was not accounted for by differential changes in psychopathology. In conclusion, stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.

Adolescent↗
PubMed2005

Impulsive aggression with irritability and responsive to divalproex: a pediatric bipolar spectrum disorder phenotype?

BACKGROUND: The objective of this retrospective chart review was to evaluate the phenomenology and response to divalproex in a sub-population of children admitted to an inpatient setting with severe impairing symptoms of irritability and aggression. In addition, we examined whether the symptomatology of this group was consistent with a pediatric divalproex-responsive bipolar spectrum disorder. METHODS: The charts of 46 child and adolescent patients with prominent impulsive aggression with irritability admitted to a crisis stabilization center were assessed retrospectively. Impulsive aggressive symptoms were assessed for admission and discharge severity by two clinicians using the Overt Aggression Scale (OAS) and the Anger-Hostility Subscale of the SCL-90 (SCL-A), with overall functioning changes assessed using the Children's Global Assessment Scale (C-GAS). RESULTS: Statistically significant improvements were obtained for the group in the C-GAS, with significant decreases in the OAS and the SCL-A scores at discharge, following a maximal 14-day stay. No severe side effects were reported. All patients met the criteria for a potential pediatric bipolar phenotype. LIMITATIONS: This was a retrospective study without randomization or a control group. Additionally, the non-blinded design may have biased the raters concerning the effectiveness of divalproex for impulsive aggression. CONCLUSIONS: Our data are in line with divalproex response in children and adolescents with target symptoms of explosive temper and mood instability. Our data further suggest that such symptoms, coupled with impulsive aggression and irritability, as well as related manic symptoms, constitute a pediatric divalproex-responsive bipolar spectrum disorder.

Adolescent↗
PubMed2005

A retrospective comparison of cumulative time spent in remission during treatment with olanzapine or risperidone among patients with schizophrenia.

BACKGROUND: Available studies suggest comparable efficacy of olanzapine and risperidone for the treatment of schizophrenia over the short term. METHOD: This retrospective analysis of data from a 28-week, double-blind, schizophrenia trial compared the cumulative amount of time that patients met severity criteria for remission during olanzapine (10-20 mg/day) or risperidone (4-12 mg/day) treatment. RESULTS: The percentage cumulative time spent in remission was 40% for olanzapine- and 31% for risperidone-treated patients (P = 0.03) using Definition 1 (PANSS items P1, P2, P3, N1, N4, N6, G5, G9 < or = 3), and 18% and 11% (P = 0.01), respectively, using Definition 2 (BPRS Total reduced 50%, BPRS psychosis items < or = 3, CGI-severity < or = 3). CONCLUSION: During 28 weeks of treatment, olanzapine-treated patients spent more cumulative time in remission than risperidone-treated patients.

Adult↗
PubMed2005

The illusion of mental health: in the mind of which beholder?

We reference self-ratings and clinician ratings of childhood anxious symptoms to a third data source well delineated with regard to the pathophysiology of anxiety. A total of 36 children with anxiety disorders and other children were administered yohimbine, an alpha-sub-2-adrenoreceptor antagonist, in response to which anxiety-prone children have blunted output of growth hormone. We assessed neuroendocrine reactions. In general, participants who claimed anxiety that was unconfirmed by clinicians displayed anxiotypic neuroendocrine profiles, whereas those who denied anxiety detected by clinicians did not, suggesting self-report may have had the advantage over clinician ratings in some instances. Nuanced and contextualized conclusions in this area of work are needed. In response to the question "the illusion of mental health: in the mind of which beholder?," we answer "it depends on the sample and the syndrome under study."

Adolescent↗
PubMed2004

Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome.

Hyperkinetic disorders may involve excess excitatory output from thalamus to cerebral cortex. Case-control, neurophysiological studies in persons with Tourette Syndrome (TS), Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD) support this model. To compare the strength of association between motor cortex inhibition and tic, ADHD, and OCD severity in TS, we used transcranial magnetic stimulation to measure motor cortex inhibition in 36 children and adults with TS. Current symptom severity was assessed with standard clinical rating scales and compared with neurophysiological measures using correlational and multivariate regression analyses. Severity of ADHD symptoms and motor tics were associated significantly and independently with short interval intracortical inhibition (SICI) (r(2) = 0.50; F[2,27] = 13.7; P < 0.001), particularly in subjects not taking neuroleptics (r(2) = 0.68; F[2,17] = 17.8; P < 0.0001). The correlation of cortical disinhibition was greater with ADHD symptoms severity (r = 0.53; P = 0.003) than with tic severity (r = 0.42; P = 0.02), suggesting that in TS, the association between SICI and ADHD symptoms may be more consistent or direct than the association between SICI and tics.

Adolescent↗
PubMed2004

The use of dietary supplements by veterans with cancer.

OBJECTIVE: To study the patterns of dietary supplement use in veterans with cancer. DESIGN: Using a detailed questionnaire, a cross-sectional study was conducted to determine the patterns of dietary supplement use by patients with cancer. SETTING/LOCATION: The study was conducted at the Hematology/ Oncology Clinic at the VA Hospital in Cincinnati, OH. SUBJECTS: Patients with malignancy who were attending the above clinic and willing to participate and sign a consent form were enrolled in the study. OUTCOMES/MEASURES: The use of dietary supplements, the type, frequency, and reason for use was captured, along with the source of dietary supplements and perceived benefits. RESULTS: Two hundred (200) veterans were surveyed, with a median age of 68 years (36-82). The type of malignancy included cancer of the genitourinary system (39.5%), lung (19.5%), gastrointestinal tract (14.5%), hematologic system (16%), skin/head/neck (6.5%), and other (4%). One hundred and twenty-two patients (122) used dietary supplements (61%). Multivitamins were the most commonly used dietary supplement reported by 98 patients (80.3%), followed by mineral use by 52 patients (40.6%). Ten (10) patients used herbal supplements. Patients who were employed and patients with higher education were more likely to use dietary supplements. Different reasons were given for dietary supplement use and 74% of the users reported perceived benefits, such as improved overall health and energy. While 38% of the patients did not disclose dietary supplement use to their physicians, 37.8% of them learned about dietary supplements from their physicians and 25% obtained their dietary supplements from the VA hospital. CONCLUSION: The use of dietary supplements is common among veterans with cancer. Health care professionals should inquire about them in a systematic fashion and be prepared to provide counseling to their patients about them.

Adult↗
PubMed2004

Tic reduction with risperidone versus pimozide in a randomized, double-blind, crossover trial.

OBJECTIVE: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. METHOD: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic motor tic disorder were randomized to 4 weeks of treatment with pimozide or risperidone, followed by the alternate treatment after a 2-week placebo washout. The primary efficacy outcome measure was change in tic severity assessed by the Yale Global Tic Severity Scale (YGTSS). ECG results, weight gain, and side effects were also compared. RESULTS: Compared to pimozide treatment, risperidone treatment was associated with significantly lower tic severity scores (YGTSS: baseline 43.3 +/- 17.5, pimozide 34.2 +/- 14.2, risperidone 25.2 +/- 13.6; p =.05). Weight gain during the 4-week treatment periods was greater for risperidone (mean 1.9 kg) than pimozide (1.0 kg). No patient suffered a serious adverse event, but 6 of 19 subjects failed to complete the protocol. Neither medication was associated with ECG changes. CONCLUSIONS: In this study, risperidone appeared superior to pimozide for tic suppression but was associated with greater weight gain.

Adolescent↗
PubMed2004

A pilot safety study of repetitive transcranial magnetic stimulation (rTMS) in Tourette's syndrome.

OBJECTIVE: We designed a randomized, blinded, crossover study to assess safety and test whether transcranial magnetic stimulation at specific regions and frequencies might modify tics. We administered repetitive transcranial magnetic stimulation over prefrontal cortex or motor cortex, with either fast or slow repetitive transcranial magnetic stimulation, to 8 Tourette's syndrome patients. METHODS: Over 5 days, we applied repetitive transcranial magnetic stimulation at 110% of the motor threshold over left motor cortex (twice) or left prefrontal cortex (twice), using either 1 Hz or 15 Hz transcranial magnetic stimulation, or sham transcranial magnetic stimulation (once). RESULTS: All 8 subjects completed the study with minimal side effects and no worsening of tics or other involuntary movements. Ignoring site and frequency, tic symptoms improved significantly over the week of the study. The study design does not allow one to address whether this was due to the presence or frequency of transcranial magnetic stimulation or to nonspecific factors involved in study participation. CONCLUSIONS: Repetitive transcranial magnetic stimulation at these sites, doses, and use parameters appears to be safe in adults with Tourette's syndrome. Further studies using repetitive transcranial magnetic stimulation in Tourette's syndrome are warranted, using balanced parallel designs.

Adult↗
PubMed2003

Donors with central nervous system malignancies: are they truly safe?

BACKGROUND: In an era of organ shortage, the use of expanded or marginal donors has been attempted to increase transplantation rates and diminish waiting list mortality. One strategy is the use of organs from patients with a history of or active central nervous system (CNS) tumor. METHODS: Sixty-two recipients were identified as the recipients of organs from donors with a history of or active CNS malignancy. Patient demographics, donor tumor management, incidence of tumor transmission, and patient survival were examined. RESULTS: Of the organs recovered and transplanted from donors with astrocytoma, 14 were associated with at least one risk factor including high-grade tumor (n=4), prior surgery (n=5), radiation therapy (n=4), and systemic chemotherapy (n=4). One tumor transmission was identified at 20 months posttransplant with the patient expiring from metastatic disease. Twenty-six organs were transplanted from glioblastoma patients with 15 demonstrating risk factors including high-grade tumor (n=9) and prior surgery (n=10). Eight transmissions were identified with a range of 2 to 15 months posttransplant, with seven patients dying as the result of metastatic disease. Seven organs were used from donors with a medulloblastoma. Three transmissions were identified at a range of 5 to 7 months, all associated with ventriculoperitoneal shunts. Two medulloblastoma recipients died as the result of metastatic disease, whereas the third is alive with diffuse disease. The rate of donor tumor transmission, in the absence of risk factors, was 7%, whereas in the presence of one or more risk factor this rate dramatically rose to 53% (P<0.01). CONCLUSIONS: Organs from donors with CNS tumors can be used with a low risk of donor tumor transmission in the absence of the following risk factors: high-grade tumors, ventriculoperitoneal or ventriculoatrial shunts, prior craniotomy, and systemic chemotherapy.

Astrocytoma↗
PubMed2003

Combination pharmacotherapy in children and adolescents with bipolar disorder.

BACKGROUND: The purpose of this study was to develop prospective data on the effectiveness of combination pharmacotherapy of children and adolescents with bipolar disorder during a 6-month period of prospective, semi-naturalistic treatment. METHODS: Thirty-five subjects, with a mean age of 11 years, were treated in the extension phase of this study after having received 6-8 weeks of acute treatment with a single mood stabilizer. The extension phase of this study lasted for another 16 weeks, for a total of 24 weeks of prospective treatment. During this study phase, subjects were openly treated, and they could have their acute-phase mood stabilizer switched or augmented with another mood stabilizer, a stimulant, an antidepressant agent, or antipsychotic agent, if they were assessed to be a nonresponder to monotherapy with their initial mood stabilizer. RESULTS: During the extension phase of treatment, 20 of 35 subjects (58%) required treatment with one or two mood stabilizers and either a stimulant, an atypical antipsychotic agent, or an antidepressant agent. The response rate to combination therapy was very good, with 80% of subjects treated responding to combination therapy with two mood stabilizers after not responding to monotherapy with a mood stabilizer. CONCLUSIONS: This study suggests that children and adolescents with bipolar disorder are similar to adults with bipolar disorder, who also frequently require combination therapy.

Adolescent↗
PubMed2003

Meta-analysis of EEG test performance shows wide variation among studies.

BACKGROUND: EEG results are used for counseling patients with seizures about prognosis and deciding on medications. Published sensitivities of interictal EEG vary widely. OBJECTIVE: To account for variation in test characteristics between studies. METHODS: Meta-analysis. Medline search, 1970 to 2000, of English language studies. Standard methods for meta-analysis of diagnostic test performance were used to determine the ability of EEG results to distinguish between patients who will and will not have seizures. Using linear regression, the authors assessed the influence of readers' thresholds for classifying the EEG as positive, sample probability of seizure, percent of subjects with prior neurologic impairment, percent treated, and years followed. RESULTS: Twenty-five studies involving 4,912 EEG met inclusion criteria. Specificity (range 0.13 to 0.99) and sensitivity (range 0.20 to 0.91) of epileptiform EEG interpretations varied widely and were heterogeneous by chi(2) analysis (p < 0.001 for each). Diagnostic accuracy of EEG and the thresholds for classifying EEG as positive varied widely. In the multivariate model, differences in readers' thresholds accounted for 37% of the variance in EEG diagnostic accuracy, and no other reported factors were significant. CONCLUSION: This analysis suggests that there is wide interreader variation in sensitivity and specificity of EEG interpretations, and that this variation influences the ability of EEG to discriminate between those who will and will not have seizure recurrences. In clinical practice, interpreting the degree to which a positive EEG result predicts increased seizure risk in an individual patient is difficult. Interpreting EEG with higher specificity yields more accurate predictions.

Adult↗
PubMed2003

Neuroendocrine and behavioral responses to dopaminergic agonists in adolescents with alcohol abuse.

RATIONALE: Dopaminergic systems are involved in the pathophysiology of alcohol use disorders, but there is little research investigating the role of these systems in adolescents. OBJECTIVES: In this study, we investigated dopaminergic systems in adolescents with alcohol abuse by determining neuroendocrine and behavioral responses to dopaminergic drug challenges. METHODS: Twenty-six participants (11 with DSM IV alcohol abuse and 15 controls) were enrolled in the study. Neuroendocrine and behavioral response to the dopaminergic indirect agonist methylphenidate (10 mg) and the direct agonist pergolide (50 mcg), were examined. The primary response measures were spontaneous eye-blink rate, plasma prolactin (PRL), and growth hormone (GH). Additionally, participants completed a visual analog mood scale (VAMS). RESULTS: The rate of increase in plasma GH level was blunted for adolescents with alcohol abuse compared to the control group, after methylphenidate administration [ t=-2.75, P=0.0066, 95% confidence interval (CI) -0.3, -0.048]. The rate of decrease in PRL level after pergolide administration was greater in adolescents with alcohol abuse as compared to the control group ( t=-3.05, P=0.0028, 95% CI -0.01923, -0.00409). Adolescents with alcohol abuse rated themselves as less "energized" in comparison to the control group after methylphenidate (rate difference=-0.4, P=0.0231). CONCLUSIONS: This preliminary study suggests that adolescents with alcohol abuse may have a differential response to dopaminergic agonists, as also reported for adults with alcohol use disorders. Further studies investigating gender differences, and other neurotransmitter systems are needed to understand the differential dopaminergic response in adolescents with alcohol use disorders.

Adolescent↗
PubMed2003

Effect of weight change on bone mass in female adolescents.

The purpose of this study was to examine changes in bone mineral density/bone mineral content (BMD/BMC) in obese female adolescents (Tanner stages 2 to 4) pursuing a weight reduction program. This was a prospective pilot clinical investigation involving 92 obese females screened to meet inclusion criteria and required to participate in a 6-month weight loss intervention. Baseline, 6 months, and 12 months measurements were taken for total body/lumbar spine BMD/BMC and percentage body fat. Survey instrumentation included the following: calcium food frequency/24-hour dietary recall, physical activity, and psychological assessments for anxiety/self-esteem. Changes in bone measurements were compared with changes in body weight measurements using multiple linear regression. Other potentially confounding variables analyzed included bone area, calcium intake, baseline Tanner stage, activity level, and height. Total body/lumbar spine BMD/BMC changes were found to be most significantly correlated with weight changes in the subject population. Although mean weight increased, the rate of increase per a given height velocity slowed to an appropriate height for weight ratio. Individuals who lost weight did not lose BMD/BMC; however, the rate of growth declined when compared with all study subjects whose bone growth rate was consistent with normal weight female adolescents. In this study, weight changes were strongly related to bone measurement changes in an obese adolescent female population. Dietitians counseling obese young girls are encouraged to emphasize the importance of a healthy weight loss program with optimal calcium intake and inclusive of weight-bearing exercises.

Absorptiometry, Photon↗
PubMed2003

Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder.

We evaluated the efficacy and toxicity of gemcitabine with or without cisplatin in 11 chemonaive patients with histologically confirmed advanced gallbladder cancer. All were symptomatic and had stage IV disease. Eight patients received gemcitabine 1 g/m2 on days 1 and 8 along with cisplatin 70 mg/m2 on day 1. Three received gemcitabine alone. Treatment cycles were repeated every 21 days. One patient (9%) had complete remission of disease and 6 (55%) achieved a partial response to chemotherapy with an overall response rate of 64%. Median time to progression was 28 weeks and median overall survival was 42 weeks. Toxicity was easily manageable, and no treatment-related deaths occurred. We conclude that gemcitabine in combination with cisplatin may be one of the most effective therapies for patients with advanced gallbladder cancer. If confirmed by others, it may provide an important therapeutic option in managing these patients who otherwise have a dismal prognosis.

Adenocarcinoma↗
PubMed2002

Phase II trial of sequential therapy with fludarabine followed by cyclophosphamide, mitoxantrone, vincristine, and prednisone for low-grade follicular lymphomas.

Advanced follicular lymphomas, grades I and II, are indolent tumors but are not considered curable with standard therapy. Fludarabine has the highest single-agent response rates in this disease. However, fludarabine-based combination chemotherapy regimens have been associated with significant myelotoxicity. Data exist suggesting that the best way to combine partially non-cross-resistant agents may be to use them sequentially. Patients with bulky stage II, stage III, or stage IV follicular lymphoma (grade I or II) were entered on this protocol. Patients were treated with 3 cycles of fludarabine followed by 6-8 cycles of cyclophosphamide, mitoxantrone, vincristine, and prednisone (CNOP). Response was assessed after the 3(rd) cycle of fludarabine and after the 4(th), 6(th), and 8(th) cycles of CNOP. Twenty-seven patients were entered on the protocol. Median follow-up was 50 months. Eighteen patients (67%) attained a complete response (CR), and eight patients (30%) attained a partial response (PR), for an overall response rate of 97%. Median relapse-free survival was 34 months, and median overall survival was not reached for the entire cohort. While all patients who achieved only PR progressed, more than half of those in CR remain free of progression at 39-84 months of follow-up. The regimen was well tolerated. The sequential combination of fludarabine and CNOP appears to be active and well tolerated in patients with grade I and II follicular lymphoma. Patients who achieve CR fare best, and many remain disease-free long term. While these results are encouraging, the addition of other active agents such as rituximab to this regimen may further enhance efficacy and is under investigation.

Adult↗