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Biomedical subjects

G Sethuraman

Publications and source records attributed to G Sethuraman.

At least 37 records · Page 2Linked to original sources

Alkaptonuric ochronosis presenting as palmoplantar pigmentation.

We describe a 37-year-old woman who presented with palmoplantar pigmentation, thickening and pitting of 4 years duration. Bluish pigmented patches were seen over the sclera of her eyes. Her lumbar spine showed typical calcification of the intervertebral discs. Addition of Benedict's reagent to a urine sample of the patient gave rise to greenish brown precipitate and brownish black supernatant. Alkalinization of urine turned it black. A biopsy of the palmar lesion demonstrated irregular breaking up, swelling and homogenization of collagen bundles in the reticular dermis. Yellow-brown (ochre coloured) pigment was seen lying within the collagen bundles and also freely in the deeper dermis confirming our clinical diagnosis of alkaptonuric ochronosis. To the best of our knowledge this is probably the second report of alkaptonuria presenting with palmoplantar pigmentation.

Adult↗

Primary pachydermoperiostosis: a case report.

Pachydermoperiostosis (PDP), a rare genodermatosis, occurred in a 38-year-old Indian male. He presented with progressive thickening of the skin on the face and scalp of 15 years duration. Widening of his wrists and ankles and broadening of the fingers and toes had also developed since then. He was born of a consanguineous marriage and had no family history of a similar disorder. He had the typical findings of complete form of PDP including cutis verticis gyrata, coarse facial features, clubbing of the digits in the skin, and periostosis and cortical thickening at the distal ends of long bones of the extremities and small bones of the hands and feet. PDP has two different forms--primary and secondary. These two entities are differentiated by family history and presence or absence of a primary lesion, usually in the lungs. Clinically, in secondary PDP, the cutaneous findings (pachydermia, seborrhoea, oiliness) are less severe than primary PDP; osteoarthropathy is more severe and painful in secondary PDP, especially with congenital heart disease. The present case was suffering from primary PDP that had expressed itself in its complete form.

Adult↗

Yohimbine challenge in children with anxiety disorders.

OBJECTIVE: The authors evaluated the neurohormonal and subjective mood response of children with anxiety disorders who were challenged with yohimbine. METHOD: Seventeen children with DSM-IV diagnoses of anxiety disorders and 15 normal comparison children were given yohimbine orally (0.1 mg/kg). Neurohormonal measures and visual analog self-reports of tenseness were recorded over a 150-minute period. RESULTS: Yohimbine was uniformly well tolerated, and it behaviorally differentiated children with anxiety disorders from normal comparison children with higher maximum change (Deltamax) ratings of anxiety in the patients (mean=17.4 mm, SD=29.8) than in the comparison subjects (mean=0.3 mm, SD=4.4). Yohimbine-stimulated Deltamax growth hormone (GH) for children with anxiety disorders (mean=-1.5 ng/ml, SD=5.9) was significantly reduced compared to that of normal comparison children (mean=2.7 ng/ml, SD=4.5). CONCLUSIONS: Yohimbine selectively elevates self-rated anxiety in children with anxiety disorders and is associated with the blunting of GH in those children relative to that of comparison children. Presence of a blunted GH response to yohimbine in children with anxiety disorders is reminiscent of findings in adults with anxiety disorders, particularly panic disorder. These findings support enhanced central adrenergic sensitivity in children with anxiety disorders, as demonstrated by yohimbine-exacerbated anxiety. The findings should be reconciled with the absence of clonidine-related GH blunting in the same cohort.

Administration, Oral↗

Validation of an instrument to measure voice-related quality of life (V-RQOL).

When a patient presents for care of a voice disorder, the clinician attempts to diagnose the problem, quantify the degree of dysphonia, and prescribe appropriate treatment. Quantification of the degree of dysphonia is often difficult, as no universal index of vocal function exists. Decisions about the nature and intensity of treatment are often based on the magnitude of the voice-related problems experienced by the patient and the importance that the patient places on those problems, that is, the impact that the voice disorder is having on the patient's voice-related quality of life (V-RQOL). Measurement of post-treatment outcome is also not standardized. Regardless of how the clinician measures response to treatment, it will typically be measured by the patient in terms of how his or her voice-related problems are affected by the treatment. Measurement of quality of life has not been a traditional part of the evaluation of the dysphonic patient. This study was undertaken to develop and validate an instrument for measuring V-RQOL using a population of 109 voice and 22 non-voice patients. The 10-item V-RQOL measure performs well in tests of reliability, validity, and responsiveness, and it carries a low burden. Measurement of V-RQOL is a valuable addition to the evaluation of dysphonic patients and their treatment outcomes.

Adult↗

Parenteral clomipramine challenge in depressed adolescents: mood and neuroendocrine response.

BACKGROUND: Major depressive disorder (MDD) in the adolescent demonstrates a unique clinical profile, and pathogenic serotonergic dysregulation is hypothesized. Parenteral clomipramine (CMI) is known to distinguish adult MDD from control, but neurochallenge data are lacking in adolescent MDD. METHODS: Thirteen drug-free outpatient adolescents who met DSM-III-R criteria for MDD were compared to adolescent controls by acute neuroendocrine and mood response to 12.5 mg of parenteral CMI. RESULTS: Repeated measures analysis revealed significant changes from baseline for sadness (p < .01) between groups, with normal controls increasing sadness rating after CMI. Prolactin (PRL) maximum change score from baseline was decreased in MDD relative to controls (p < .05). Gender effects on PRL were evident in controls but not in MDD. CONCLUSIONS: The findings of PRL blunting in adolescent MDD mirrors previous work in adults. A unique finding is the induction of sadness in normal adolescent controls after CMI infusion.

Adolescent↗

Intravenous clomipramine challenge in obsessive-compulsive disorder: predicting response to oral therapy at eight weeks.

BACKGROUND: Challenge with intravenous clomipramine (CMI) is serotonin selective and has been reported to transiently exacerbate symptoms in obsessive-compulsive disorder (OCD) patients, and to predict subsequent response to oral CMI therapy. METHODS: We administered CMI (12.5 mg, i.v.) to medication free OCD patients (N = 29) and normal controls (N = 22) to characterize neurohormonal response. A subset of OCD patients (26/29), was then treated with either pulse load i.v. or oral CMI followed by 8 weeks of oral CMI therapy. RESULTS: In response to CMI challenge, OCD patients exhibit blunted cortisol and exaggerated growth hormone response relative to normal controls. OCD patients differ from controls in "sadness" ratings, with control exhibiting increased dysphoria in response to CMI. Growth hormone response to CMI challenge predicts treatment response (> or = 25% decreases YBOCS from baseline) to oral CMI at 8 weeks. CONCLUSIONS: Growth hormone abnormalities associated with OCD in response to CMI challenge differentiates nonresponders after 8 weeks of oral CMI treatment from responders.

Administration, Oral↗

Clonidine challenge in childhood anxiety disorder.

OBJECTIVE: To evaluate the neurohormonal and subjective mood response of children with anxiety disorder to clonidine challenge METHOD: Children with DSM-IV diagnoses of anxiety disorder (ANX) (n = 24) and normal controls (n = 15) were given a challenge of intravenous clonidine (1.3 micrograms/kg) and provided neurohormonal and mood self-report assessment over a 180-minute period. RESULTS: The ANX group differed from normal controls in Hamilton Anxiety Rating, Revised Children's Manifest Anxiety Scale score, and maximum change from baseline (delta max) in growth hormone (GH). Clonidine-stimulated GH concentration of the ANX group was significantly elevated compared with that of controls but returned to baseline within 2 hours. A subgroup with obsessive-compulsive disorder (OCD) (n = 9) had significantly higher delta max GH (17.5 +/- 10.1 ng/mL) than the group with other anxiety disorders (ANX-OCD) (9.1 +/- 5.8 ng/mL) and controls (5.7 +/- 4.1 ng/mL). CONCLUSION: GH response to clonidine challenge is not blunted in ANX subjects. This finding is in contrast to adult disorder and suggests that adrenergic postsynaptic receptor down-regulation is not a feature of childhood anxiety. These findings suggest enhanced central adrenergic sensitivity in ANX which is most pronounced in OCD and argue against a neurobiological continuum from childhood to adult anxiety disorder.

Adolescent↗

The Crystallization of Fluorapatite in the Presence of Hydroxyapatite Seeds and of Hydroxyapatite in the Presence of Fluorapatite Seeds

The kinetics of growth of crystals induced by hydroxyapatite (HAP) seed crystals in supersaturated solutions of fluorapatite and of fluorapatite (FAP) seed crystals in supersaturated solutions of hydroxyapatite have been studied using the constant composition method. The reactions were investigated at relative supersaturations ranging from sigmaFAP = 0.99 to 12.0 at pH 6.5 and for HAP, sigmaHAP = 3.6 to 12.6 at pH 7.4. In FAP-supersaturated solutions, this phase was nucleated at the HAP surfaces and underwent growth at a rate more than three times greater than that on FAP seed crystals of equivalent surface area. Transmission electron microscopy (TEM) and electron diffraction imaging clearly demonstrated that the new needle-like HAP phase originated at the FAP surface with the 002 planes of HAP growing on FAP. In contrast, the mutual orientation of FAP crystallization on HAP seed crystals could not be established. Interfacial energies of FAP, HAP, and octacalcium phosphate (OCP) microcrystals against aqueous solutions were obtained by using a thin-layer wicking technique. The interfacial energy values measured in pure aqueous solutions were 18.5, 9.0, and 4.3 mJ m-2 for FAP, HAP, and OCP, respectively. The much smaller value for OCP as compared with the other phases may explain why this phase has been so frequently implicated as a possible precursor to the formation of apatite, especially in biological mineralization reactions.

Journal Article↗

Dopamine agonist treatment of Tourette disorder in children: results of an open-label trial of pergolide.

This exploratory study was meant to determine the effect of the dopamine (DA) agonist pergolide on Gilles de la Tourette syndrome (GTS) in children and adolescents and to ascertain correlates of pergolide response. Thirty-two outpatients, aged 7-19 years, were systemically assessed in a neuropsychiatric clinic for the presence of GTS and comorbid disorders. After a 6-week open-label, fixed-flexible dosing schedule, response to pergolide on standard GTS severity outcome measures was assessed. Overall, 75% of patients (24/32) had a > 50% drop in their tic severity rating from baseline with a mean treatment dosage of 177 +/- 61 micrograms/day. Highly significant (p = 0.0001) baseline to week 6 differences were demonstrated in all tic symptom measures. The presence of restless legs syndrome (RLS) comorbidity (59%) was highly associated with a positive response. These results suggest DA agonism as a strategy, and pergolide in particular, may be a practical form of therapy for GTS. Response predictors of patient comorbid RLS argue for its further study with regard to GTS.

Adolescent↗

Pulse intravenous clomipramine for depressed adolescents: double-blind, controlled trial.

OBJECTIVE: Major depressive disorder in adolescents is characterized as treatment resistant, but a previous open-label trial of pulse intravenous clomipramine demonstrated rapid relief of depressive symptoms. In the present study a single intravenous dose of clomipramine (200 mg) was compared with saline placebo in a randomized controlled trial for depressed adolescents. The hypothesis was that adolescents who were treated with pulse clomipramine would exhibit lower scores on the Hamilton Depression Rating Scale at endpoint than would adolescents who received saline and that clomipramine would be superior to saline in terms of antidepressant response. METHOD: Sixteen nonsuicidal outpatient adolescents (mean age = 16.2 years, SD = 1.0) who met the DSM-III-R criteria for major depression (score on 21-item Hamilton scale, > or = 18) were randomly assigned to receive either clomipramine (200 mg i.v., N = 8) or saline (N = 8). Assessments of depression severity were completed 36 hours and 6 days thereafter. RESULTS: The adolescents who received pulse clomipramine treatment demonstrated significant decreases in Hamilton depression scores from baseline at 6 days but not at 36 hours. A similar decrease from baseline was found in Clinical Global Impression severity at 6 days but not 36 hours. Seven of the clomipramine-treated patients and three of the saline-treated patients had drops of 50% or more from baseline in Hamilton depression score. CONCLUSIONS: Pulse clomipramine (200 mg i.v.) is associated with dramatic reduction in depressive symptoms at day 6 after infusion, which is significantly different from the effect of placebo.

Adolescent↗

Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette's disorder.

OBJECTIVE: The authors evaluated the relative efficacy and safety of pimozide and haloperidol in the treatment of Gilles de la Tourette's syndrome in children and adolescents. METHOD: A double-blind, 24-week, placebo-controlled double crossover study of equivalent dose formulations of haloperidol and pimozide was conducted with 22 subjects, aged 7-16 years, with Tourette's disorder who were randomly assigned to first one active drug treatment and then the other. Biweekly assessment and flexible dose titration mimicked clinical practice. The primary outcome variable was total score on the Tourette Syndrome Global Scale. Final outcome was determined after 6 weeks of each treatment (placebo, pimozide, haloperidol), with a 2-week placebo baseline period and intervening 2-week placebo washout periods between treatments. RESULTS: Pimozide proved significantly different from placebo in affecting the primary outcome variable, whereas haloperidol failed to have a significant effect. Haloperidol exhibited a threefold higher frequency of serious side effects and significantly greater extrapyramidal symptoms relative to pimozide. Haloperidol-associated treatment-limiting adverse events were experienced by 41% of the patients. The therapeutic doses of pimozide and haloperidol were equivalent (mean = 3.4 mg/day, SD = 1.6, and mean = 3.5 mg/day, SD = 2.2, respectively). CONCLUSIONS: At equivalent doses, pimozide is superior to haloperidol for controlling symptoms of Tourette's disorder in children and adolescents.

Adolescent↗