Higher concentrations of vitamin D in Canadian children with juvenile idiopathic arthritis compared to healthy controls are associated with more frequent use of vitamin D supplements and season of birth.

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA).  The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents.

Clinical and psychosocial stress factors are associated with decline in physical activity over time in children with juvenile idiopathic arthritis.

Background: Physical activity (PA) patterns in children with juvenile idiopathic arthritis (JIA) over time are not well described. The aim of this study was to describe associations of physical activity (PA) with disease activity, function, pain, and psychosocial stress in the 2 years following diagnosis in an inception cohort of children with juvenile idiopathic arthritis (JIA).

Methods: In 82 children with newly diagnosed JIA, PA levels, prospectively determined at enrollment, 12 and 24 months using the Physical Activity Questionnaire for Children (PAQ-C) and Adolescents (PAQ-A) raw scores, were evaluated in relation to disease activity as reflected by arthritis activity (Juvenile Arthritis Disease Activity Score (JADAS-71)), function, pain, and psychosocial stresses using a linear mixed model approach.

Soluble Low-density Lipoprotein Receptor-related Protein 1 in Juvenile Idiopathic Arthritis.

Objectives: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.

Methods: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.

Associations of clinical and inflammatory biomarker clusters with juvenile idiopathic arthritis categories.

Objective: To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories.

Methods: A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers.

Correction to: Hypophosphatasia: Canadian update on diagnosis and management.

In the article mentioned above an author's name was misspelled.

Hypophosphatasia: Canadian update on diagnosis and management.

Unlabelled: Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism caused by loss of function mutations in the ALPL gene. The presentation in children and adults can be extremely variable and natural history is poorly understood particularly in adults. Careful patient evaluation is required with consideration of pharmacologic intervention in individuals meeting criteria for therapy.

Intra-ocular pressure variation associated with the wear of scleral lenses of different diameters.

Purpose: To evaluate the variation of intra-ocular pressure during scleral lens wear, and the influence of the lens diameter on the results.

Methods: This is a prospective, randomized study performed on Caucasian subjects (16 F; 5 M), aged 24.7 + 4.

A prospective evaluation of an interdisciplinary nutrition-rehabilitation program for patients with advanced cancer.

Background: Cancer can affect many dimensions of a patient's life, and in turn, it should be targeted using a multimodal approach. We tested the extent to which an interdisciplinary nutrition-rehabilitation program can improve the well-being of patients with advanced cancer.

Methods: Between January 10, 2007, and September 29, 2010, 188 patients with advanced cancer enrolled in the 10-12-week program.

Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers.

Background: For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice.

Methods: A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used to develop the MPS.

Bone remodeling in postmenopausal women who discontinued denosumab treatment: off-treatment biopsy study.

Denosumab is a fully human monoclonal antibody that neutralizes the activity of RANKL, leading to the inhibition of osteoclast maturation, bone-resorbing activity, and survival. Evaluation of trans-iliac crest bone biopsy specimens in the phase 3 pivotal fracture study with denosumab in postmenopausal women with osteoporosis showed evidence of reduced bone turnover at the tissue level in subjects receiving denosumab, and up to one-third of subjects did not have evidence of tetracycline labeling in trabecular or cortical bone. Discontinuation of denosumab therapy has demonstrated that the effects of denosumab are reversible, as assessed by biochemical markers of bone turnover (BTM) and BMD.

Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial.

Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, doubleblind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score View Article and Find Full Text PDF

Alendronate once weekly for the prevention and treatment of bone loss in Canadian adult cystic fibrosis patients (CFOS trial).

Background: Patients with cystic fibrosis (CF) are at risk for early bone loss, and demonstrate increased risks for vertebral fractures and kyphosis. A multicenter, randomized, controlled trial was conducted to assess the efficacy, tolerability, and safety of therapy with oral alendronate (FOSAMAX; Merck; Whitehouse Station, NJ) in adults with CF and low bone mass.

Methods: Participants received placebo or alendronate, 70 mg once weekly, for 12 months.

The use of dexamethasone to reduce pain after tonsillectomy in adults: a double-blind prospective randomized trial.

Objectives/hypothesis: To determine the effectiveness of dexamethasone to reduce pain after tonsillectomy in adults by at least 13 mm on the visual analogue scale. The secondary objective was to reduce the use of narcotics by at least 20%.

Study Design: This multicentric study is a prospective double-blind randomized controlled trial.

Palliative laparoscopic resections for Stage IV colorectal cancer.

Purpose: Issues surrounding the safety and efficacy of palliative laparoscopic resections for patients with Stage IV colorectal cancer have not been explicitly examined in the literature. This article describes our experience with laparoscopic procedures for patients with Stage IV colorectal cancer and compares their perioperative outcomes to a contemporaneous group of patients with clinically curable (Stages I-III) disease.

Methods: A prospective database of laparoscopic resections for colorectal cancer performed between 1991 and 2002 was reviewed.

Dyskinesias occur in response to saline and naltrexone alone after priming with combination of dopaminergic agents and naltrexone in the MPTP parkinsonian monkeys.

Storage of motor memory involves the basal ganglia and more precisely the striatum, which receives afferents from all regions of the cerebral cortex. In Parkinsonian (MPTP) monkeys, we observed an increase in the dyskinetic response to dopaminergic agents when combined with opioid antagonists (naloxone or naltrexone) while morphine, attenuated the dyskinetic response. An interesting phenomenon observed after several acute co-administrations of naltrexone with dopaminergic agents was the manifestation of dyskinesias even after the injection of saline or naltrexone alone.

Opioid antagonists increase the dyskinetic response to dopaminergic agents in parkinsonian monkeys: interaction between dopamine and opioid systems.

The pathogenesis of levodopa-induced dyskinesias (LID) still remains obscure. It has been suggested that enhanced opioidergic transmission in striatal output pathways may play a role in the induction of LID. To test this hypothesis, we have investigated the effect of different doses of the opioid receptor antagonists, naloxone and naltrexone on the dyskinetic response to a D1 agonist SKF 82958, a D2 agonist quinpirole and L-3,4-dihydroxyphenylalanine (L-Dopa).

Methodology to determine duration of action for antihypertensive drugs.

Objective: To review and comment on methods used to assess the duration of action of antihypertensive drugs.

Data Sources: A MEDLINE search (1966-June 2000) using key terms such as trough-to-peak ratio and ambulatory blood pressure monitoring was conducted.

Study Selection: An article was considered for this review if it pertained to the assessment of the duration of action of antihypertensive drugs.

Stereospecific prevention by 17beta-estradiol of MPTP-induced dopamine depletion in mice.

Neuroprotective activity of estrogens is reported in Alzheimer disease and recently has also been suggested for Parkinson disease, a disease affecting more men than women. To characterize this estrogenic activity, we studied the effects of 17beta- and 17alpha-estradiol treatment (1 microg twice daily 5 days before, during the day of four MPTP (15 mg/kg) injections, and for the following 5 days) on dopamine striatal toxicity induced by the neurotoxin MPTP in retired breeder male C57BL/6 mice. Striatal dopamine concentrations and its metabolites dihydroxyphenylacetic acid and homovanillic acid measured by HPLC in MPTP mice that received 17beta-estradiol were comparable to control animals, whereas MPTP mice treated with saline or 17alpha-estradiol showed important decreases of dopamine and its metabolites.

Molecular basis of levodopa-induced dyskinesias.

A series of experiments were performed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism for the purpose of understanding the mechanism of dopaminergic dyskinesias. Dyskinesias can be induced in this model by de novo treatment with levodopa, or selective D1 or D2 agonists, provided the drugs are short acting and administered in the pulsatile mode. Biochemical analysis of the brains revealed several alterations in dopamine receptor-binding and messenger RNA message following denervation and dopaminergic treatment, but none that clearly correlated with the presence of dyskinesias.

Improvement of pagetic bone lesions with risedronate treatment: a radiologic study.

Risedronate is a potent pyridinyl bisphosphonate in clinical development for treatment and prevention of osteoporosis, and has been recently approved for treatment of Paget's disease in the United States. An open-label study was conducted to determine the effect of risedronate treatment on pagetic bone lesions in patients with moderate to severe Paget's disease (mean serum alkaline phosphatase levels [ALP] approximately seven times the upper limit of normal). Patients were treated with 30 mg/day oral risedronate for 84 days followed by a 112-day nontreatment period.

Androgen receptor antagonists (antiandrogens): structure-activity relationships.

Prostate cancer, acne, seborrhea, hirsutism, and androgenic alopecia are well recognized to depend upon an excess or increased sensitivity to androgens or to be at least sensitive to androgens. It thus seems logical to use antiandrogens as therapeutic agents to prevent androgens from binding to the androgen receptor. The two predominant naturally occurring androgens are testosterone (T) and dihydrotestosterone (DHT).

Differential androgen sensitivity is associated with clonal heterogeneity in steroid metabolism, ornithine decarboxylase regulation and IL-1alpha action in mouse mammary tumor cells.

Upon androgen deprivation, Shionogi (SC-115) mouse mammary tumors undergo phenotypic changes enabling their escape from growth dependence on androgens. Even within androgen-responsive cell populations, marked clonal heterogeneity is observed in the trophic effects of androgens. The present study compares several parameters of androgen action between three SC-115 cell clonal subpopulations exhibiting high (clone 107), low (clone S1A2) and no trophic response (clone 415) to androgens.

Effect of dehydroepiandrosterone and its sulfate and fatty acid ester derivatives on rat brain membranes.

The effects of dehydroepiandrosterone (DHEA) as well as its sulfate and fatty acid ester derivatives on rat brain membrane fluidity was investigated by fluorescence depolarization of a lipid probe 1,6-diphenyl-1,3,5-hexatriene and compared to its effect on phospholipid conformation investigated by Fourier transform infrared spectroscopy. In rat brain, membrane fluidity varied rostro-caudally, the frontal cortex showing the highest fluidity compared to the hypothalamus, hippocampus, striatum, thalamus, and hindbrain. As previously reported, it was observed that cholesteryl hemisuccinate and stearic acid rigidify striatal membrane whereas linoleic acid and L-alpha-phosphatidylcholine increase the membrane fluidity.

Effect of estradiol and tamoxifen on brain membranes: investigation by infrared and fluorescence spectroscopy.

Nongenomic effects of steroids on rat brain neurotransmitter transporters and receptors have been reported in several laboratories. In the present study, we have investigated possible membrane effects of 17alpha- and 17beta-estradiol, as well as tamoxifen, by studying their interactions with synthetic phospholipid membranes using Fourier transform infrared spectroscopy. We have also used the fluidity of rat striatal and frontal cortex membranes, as determined by fluorescence depolarization of the probe 1,6-diphenyl-1,3,5-hexatriene (DPH), to probe the effects of these drugs on membranes.