Reference intervals for free thyroxine, total triiodothyronine, thyrotropin and thyroglobulin for Quebec newborns, children and teenagers

OBJECTIVE: Paediatric reference values, although essential for interpreting patients' results, are scarce. Moreover, they are often population- and instrument-dependent. We have measured free thyroxine (Free T(4)), total triiodothyronine (Total T(3)), thyroglobulin (Tg) and thyrotropin (TSH) in samples obtained from groups of newborns, children and adolescents. SUBJECTS AND METHODS: Blood samples collected from healthy children and teenagers (100 girls and 100 boys) of age groups ranging between 9-10, 11-14 and 15-17 years and selected randomly from a cohort representative of the Quebec population, were used. Samples from infants of age ranging between 1 day and 2 years (n = 99) were obtained from a hospital-based population with benign conditions unlikely to affect thyroid function. Variables were measured on the Access 2 immunosystem. RESULTS: Free T(4), Tg and TSH levels declined significantly with age. However, Total T(3) level presented a nonlinear variation with age, being lower in the first month of life.     

Measurement of the serotonin 1A receptor availability in patients with schizophrenia during treatment with the antipsychotic medication ziprasidone

The aim of this study was to compare 5-HT(1A) availability in vivo in individuals with schizophrenia before and during treatment with the atypical antipsychotic ziprasidone. Six individuals with schizophrenia underwent two PET scans with [(11)C]WAY 100635; the first while medication-free (baseline) and the second while taking the atypical antipsychotic ziprasidone (on-medication). Regional volumes of distribution (V(T), mL g(-1)) were derived using a two-tissue compartment kinetic model. Outcome measures included binding potential relative to the plasma (BP(P), mL g(-1)) and the binding potential relative to the nonspecific distribution volume (BP(ND), unitless). No significant differences were observed in regional BP(P) or BP(ND) with ziprasidone treatment. A significant correlation was noted between BP(P) measured in the orbitofrontal cortex during the on-medication condition and degree of improvement in negative symptoms with treatment (r?=?0.96, p?=?0.004). Consistent with the published literature of changes in 5-HT(1A) binding during treatment with 5-HT(1A) receptor agonists, this study did not detect a significant reduction in 5-HT(1A) binding with ziprasidone. The finding of a relationship between 5-HT(1A) binding and the degree of improvement in negative symptoms provides further support for the role of the 5-HT(1A) receptor in the pathophysiology and treatment of this symptom domain.     

Imaging the neurochemistry of alcohol and substance abuse

Animal models of abuse and dependence have long suggested that chronic drug and alcohol exposure is associated with marked changes in neurochemistry. The development of PET and SPECT imaging now allows investigation of the effects of addiction on the neurochemistry of the human brain. This article reviews the literature of radiochemical imaging in cocaine, alcohol, heroin, methamphetamine, MDMA, and ketamine abuse and dependence.     

Self‐reported daily stress,squelching of anger and the management of daily stress and the prevalence of uterine leiomyomata: the ultrasound screening study

Self‐reported daily stress, ways of managing stress and squelching anger were examined in association with uterine leiomyomata (aka fibroids). These stress factors were obtained from 560 Black and 375 White women enrolled in the National Institute of Environmental Health Sciences Uterine Fibroid Study. Race‐specific prevalence differences (PD) and 95% confidence intervals (95% CI) were calculated. Black women with severe stress had a prevalence of fibroids that was 11% higher (95% CI: 0%, 21%) than those in the no or mild stress group (referent). White women with severe stress, compared to the referent, had a non‐significantly (NS) higher prevalence of fibroids [PD = 7%; 95% CI: (?10%, 21%)]. For both groups, moderate daily stress was associated with a weak elevation (NS) in fibroid prevalence. Black women who reported squelching their anger had an elevated prevalence of fibroids (8%) compared to non‐squelchers [95% CI: (?0%, 15%)] while there was no association for White women. Women with symptomatic fibroids had higher stress than those without, but exclusion of symptomatic women only slightly attenuated the associations. Consistent with a previous report, symptomatic fibroids may cause stress. However, further research is warranted to prospectively investigate a possible aetiologic role for stress in the development of fibroids. Copyright © 2010 John Wiley & Sons, Ltd.     

Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans

 Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with psychotogenic and dissociative effects in healthy humans. These cognitive and perceptual effects in humans are reportedly reduced by benzodiazepine premedication. This study assessed the interactive effects of a ketamine (IV bolus of 0.26 mg/kg followed by an infusion of 0.65 mg/kg per hour) and lorazepam 2 mg., PO, in humans. Twenty-three healthy subjects completed 4 test days involving the oral administration of lorazepam or matched placebo 2 h prior to the IV infusion of ketamine or placebo. Ketamine: 1) produced behaviors similar to the positive and negative symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale (BPRS); 2) evoked perceptual alterations as measured by the Clinician-Administered Dissociative States Scale (CADSS); 3) impaired performance on the Wisconsin Card Sorting Test (WCST) and other tests sensitive to frontal cortical impairment; and 4) had amnestic effects. Lorazepam produced attention impairments, concrete proverb interpretations, and recall impairments. Lorazepam reduced ketamine-associated emotional distress and there was a non-significant trend for it to decrease perceptual alterations produced by ketamine. However, it failed to reduce many cognitive and behavioral effects of ketamine, including psychosis. Further, lorazepam exacerbated the sedative, attention-impairing, and amnestic effects of ketamine. There was no evidence of pharmacokinetic interaction between these medications. These data suggest that subhypnotic lorazepam and ketamine show a spectrum of interactive effects, ranging from antagonism to potentiation. Received: 1 April 1996/Final version: 20 May 1997     

A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference

BackgroundPreclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells.MethodsSingle-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean ± SD age, 26.3 ± 7.7 years) homozygous for the F508del mutation received oral miglustat 200 mg t.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference.ResultsNo statistically significant changes in TCS, sweat chloride values or FEV₁ were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat.ConclusionsThere was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference.