Search for genes involved in Joubert syndrome: evidence that one or more major loci are yet to be identified and exclusion of candidate genes EN1, EN2, FGF8, and BARHL1.

Joubert syndrome (JS) is a rare autosomal recessive malformation syndrome involving agenesis or dysgenesis of the cerebellar vermis with accompanying brainstem malformations. JS is further characterized by hypotonia, developmental delay, intermittent hyperpnea, and abnormal eye movements. The biochemical and molecular basis of JS remains unknown, although several genes that are crucial in the development of the cerebellum have been proposed as attractive candidate genes. JS is clinically heterogeneous; this, together with previous linkage analyses, suggests that there may also be genetic heterogeneity. A locus for JS was previously identified on chromosome 9q34 by linkage analysis in a consanguineous family of Arabian origin. A putative second JS locus was recently suggested when a deletion on chromosome 17p11.2 was observed in a patient with Smith-Magenis syndrome and JS phenotype. We have investigated a cohort of apparently unrelated North American JS pedigrees for association with the loci on chromosomes 9q34 and 17p11.2 and excluded them in all cases where data were informative. Analysis of an additional 21 unrelated JS patients showed no evidence of homozygosity at the 9q34 and 17p11.2 loci that would suggest inheritance of founder JS mutation(s) or unreported consanguinity. Together, these data suggest that one or more major loci for JS remain to be identified. Consequently, we undertook mutation analysis of several functional candidate genes, EN1, EN2, and FGF8, in a total of 26 unrelated JS patients. Our data suggest that all of these genes may be excluded from a direct pathogenic role in JS. The BARHL1 gene, which localizes to chromosome 9q34 and has previously been proposed as a strong positional candidate gene for JS, was also investigated and excluded from involvement in JS that is linked to chromosome 9q34.     

Mapping myocardial viability using interleaved T 1—T 2 * weighted imaging

The present study was to evaluate the efficacy of our interleaved T1-T2* weighted imaging for assessing myocardial viability. The left anterior descending coronary artery (LAD) of pig hearts (n = 7) were occluded for 2 h, followed by 1 h reperfusion. After removed from animals, the hearts were perfused in a Langendorff apparatus with a mixture of pig blood and crystalloid solution in 1:1 ratio. T1 relaxation times of the myocardium were measured with a TurboFLASH inversion-recovery sequence. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.05 mmol/kg body wt) was then injected as a bolus into the aortic perfusion line. The first pass of the contrast agent through the heart was followed using the interleaved T1-T2* imaging sequence. Once the concentration of the contrast agent was in an equilibrium state, T1 relaxation times were measured again. It was found that the percentage recovery of T2* intensity (PRT2*) at the maximum T1 intensity measured during the first pass of the contrast agent with the interleaved T1-T2* imaging was significantly higher in infarcted myocardium than in normal myocardium. Moreover, the regions showing a high T2* percentage recovery on PRT2* maps matched well with the infarcted myocardium demarcated with triphenyl tetrazolium chloride (TTC) staining. We therefore conclude that infarcted myocardium can be delineated using the interleaved T1-T2* imaging method.     

Putting evidence into practice: evidence-based interventions to prevent, manage, and treat chemotherapy-induced nausea and vomiting

Chemotherapy-induced nausea and vomiting (CINV) continues to have a considerable effect on the physical and psychological well-being of patients with cancer, despite significant advances in antiemetic drugs since the 1990s. This article reviews and summarizes past and current empirical evidence related to interventions for CINV. A resource that summarizes evidence-based interventions for CINV is critical for effective management of this distressing symptom. Pharmacologic and nonpharmacologic interventions are appraised. Finally, gaps in the literature and opportunities for research, education, and practice changes are discussed.     

Acute musculoskeletal pain in the emergency department: a review of the literature and implications for the advanced practice nurse

Acute pain assessment and management and their accurate documentation have been identified by The Joint Commission on the Accreditation of Healthcare Organization as significant components of the emergency department experience. Research studies have historically focused on the subjective perception of the physician or nurse for evidence of acute musculoskeletal pain assessment for the patient; however, the lack of interrater reliability between caregivers and patients has illustrated the need to evaluate the patient's perception of pain. A review of the literature for acute musculoskeletal pain in the emergency department shows that a patient's pain experience is often underestimated, and severity of pain often does not predict pain management. Relying on patient satisfaction surveys as a surrogate marker for effectiveness of pain management is inadequate, and factors, such as age, gender, or ethnicity, may contribute to a disparity in pain management. The purpose of this article is to review pain management practices for patients with acute musculoskeletal pain who present to the emergency department and to provide recommendations for advanced practice nurses working with this emergency department patient population. Promising areas for future research include targeting mechanisms of pain with specific medications, identifying vulnerable populations at risk for inadequate pain management, and universal use of a standardized pain rating scale.     

Add-on Treatment of Quetiapine for Fibromyalgia: A Pilot, Randomized, Double-Blind, Placebo-Controlled 12-Week Trial

ABSTRACT: Recently, second-generation antipsychotic drugs have attracted interest in the treatment of chronic pain, including fibromyalgia (FM). Preliminary uncontrolled studies have shown that quetiapine treatment may be helpful for FM patients. In this trial, we sought to examine-for the first time-the efficacy and tolerability of quetiapine as a treatment for FM and its associated psychiatric symptoms. This was a 12-week double-blind, randomized, placebo-controlled trial of quetiapine XR as an add-on treatment for FM syndrome. Fifty-one female FM patients were randomized, and a flexible dosage of 50 to 300 mg/d was used. The primary outcome was the change from baseline to end point in the Fibromyalgia Impact Questionnaire total score. Secondary outcomes included mood symptoms, sleep disturbances, and tender points. Using a low dose (mean = 132.2 mg) of quetiapine, we observed significant benefits of drug treatment on sleep, uncertain effects on FM and mood symptoms, but no effects on pain, in a small group of polymedicated FM patients. Quetiapine was generally well tolerated.