Motivational Interviewing: How Advanced Practice Nurses Can Impact the Rise of Chronic Diseases

The Centers for Disease Control and Prevention states that almost 1 of every 2 adults in the United States has at least 1 chronic disease. Traditional methods of patient education, like providing expert advice, are not halting the rise of chronic diseases or risky health behaviors. This article provides an overview of motivational interviewing (MI) and how it can be an alternative to traditional educational methods for increasing patients’ internal motivation to change. Advanced practice nurses can play a pivotal role in decreasing the rise of chronic diseases by incorporating MI into patient care.     

Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development

Mutations in the human L1CAM gene cause X‐linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1^KO) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin‐binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1^KO mice, yet it is required for continued L1 protein expression and motor function in the adult. J. Comp. Neurol. 518:1113–1132, 2010. © 2009 Wiley‐Liss, Inc.     

Flunarizine pretreatment attenuates hyperthermia-induced extravasation in rats

Previous work has established that there is an increase in endothelial permeability in hyperthermic rats. This work assessed the potential of the calcium channel blocker (E)-1-bis(4-fluorophenyl)methyl-4-(3-phenyl-2-propenyl)piperazine dihydrochloride (flunarizine) as a pretreatment to ameliorate this extravasation. Five groups of male rats (n=12 rats per group, 400-500 g) were given 0, 0.3, 1, 2, or 3 mg/kg flunarizine (FL0, FL0.3, FL1, FL2, and FL3, respectively) by gavage 30 min prior to induction of hyperthermia. Hyperthermia was achieved by placing unrestrained animals in their own cages in a chamber maintained at 41.5 degrees C until a core temperature (Tc) of 42.6 degrees C was attained. Then, 25 mg/kg of Evans blue in saline was administered via a jugular cannula. After 15 min the animals were anesthetized, exsanguinated, tissues removed and washed in saline, and Evans blue extracted with formamide. As the dose of flunarizine was increased, there was a significant (P<0.05) reduction of Evans blue recovered from the liver, kidney, lung, spleen, and intestinal tissue. Endurance time in the heat to reach a Tc of 42.6 degrees C increased significantly from 194+/-39 min (mean+/-SD) with FL0 to 275+/-33 min with FL1, but decreased again with FL2 (206+/-42) and FL3 (199+/-60). Thus, flunarizine pretreatment attenuated hyperthermia-induced extravasation, and 1 mg/kg flunarizine markedly increased the tolerance time to heat exposure.     

Ontogeny of the neutral amino acid transporter SAT1/ATA1 in rat brain

The glutamine-glutamate/GABA cycle is critical for the developing brain as glutamatergic neurotransmission is important for neuronal survival and drives synaptogenesis and activity-dependent synaptic plasticity. GABAergic transmission may be essential for the formation of neural circuits. Recently a cDNA encoding a brain-enriched System A transporter (SAT1/ATA1), has been identified which may provide glutamine to neurons for the biosynthesis of neurotransmitters glutamate and gamma-aminobutyric acid (GABA). In this study, we have examined the developmental expression pattern of SAT1/ATA1 protein in rat brain by immunohistochemistry. We find that SAT1/ATA1 was present in the developing rat brain at all gestational ages examined including prenatal days 17 and 19 and postnatal days 2, 10, 14, and adult. SAT1/ATA1 immunoreactivity was seen in the neocortex, hippocampus, and neuroepithelium at the earliest time point examined, prenatal day 17. SAT1/ATA1 was prominent in the striatum, the hippocampus and the cortex in the postnatal animals. In adults, SAT1/ATA1 was limited to the cell body region while in developing animals SAT1/ATA1 protein was found in neuronal processes. These results contribute to our understanding of the relationship between the cycling of glutamate and glutamine between astrocytes and glia and the pathophysiological conditions that occur in hypoxic ischemic encephalopathy.     

Calcitriol (1,25-dihydroxycholecalciferol) potentiates activity of mitoxantrone/dexamethasone in an androgen independent prostate cancer model

PURPOSE: Mitoxantrone combined with glucocorticoids is widely used for androgen independent prostate cancer. It is well tolerated, reduces prostate specific antigen, diminishes pain and improves quality of life. Calcitriol (1,25-dihydroxycholecalciferol) inhibits proliferation, modulates cell cycle progression, induces apoptosis and potentiates the cytotoxic effects of a number of agents. Glucocorticoids potentiate the antitumor effects of calcitriol and blunt calcitriol induced hypercalcemia. Therefore, we investigated the effect of calcitriol on the antitumor efficacy of mitoxantrone and dexamethasone or mitoxantrone/dexamethasone in the PC-3 androgen independent prostate cancer model. MATERIALS AND METHODS: We treated PC-3 cells in vitro with various concentrations of mitoxantrone/dexamethasone with and without calcitriol, and assessed growth inhibition by crystal violet assays. We similarly treated mice bearing PC-3 xenografts and performed excision clonogenic assays and tumor outgrowth studies to assess antitumor activity. RESULTS: Calcitriol significantly increased mitoxantrone/dexamethasone mediated growth inhibition in PC-3 cells (p <0.05). Median dose effect analysis indicated that calcitriol is synergistic with mitoxantrone. Adding calcitriol to mitoxantrone/dexamethasone significantly reduced the surviving fraction per gm. tumor compared with mitoxantrone/dexamethasone or untreated controls (p <0.03). Calcitriol plus mitoxantrone/dexamethasone also caused significantly greater tumor regression in PC-3 xenografts compared with treatment with mitoxantrone/dexamethasone or untreated controls (p <0.02). CONCLUSIONS: These preclinical data demonstrate that calcitriol increases the antitumor activity of mitoxantrone/dexamethasone in the PC-3 model system. This combination may be efficacious for prostate cancer.     

Decreased tumor blood flow as measured by positron emission tomography in cancer patients treated with interleukin-1 and carboplatin on a phase I trial

BACKGROUND: Positron emission tomography (PET) scanning can be used to measure blood flow. When interleukin-1alpha (IL-1) is given in a murine model, it induces acute hemorrhagic necrosis, tumor vascular injury and decreased tumor blood flow, and when given prior to carboplatin, there is enhanced antitumor activity compared to either agent alone. METHODS: In a phase I trial of IL-1 and carboplatin, eligible patients with metastatic disease to the lung had PET scanning performed with (15)O water to assess tumor blood flow before and after IL-1 administration. Doses of IL-1 were 0.03, 0.06, 0.10, 0.15, 0.20 and 0.30 micro g/kg given i.v. over 2 h. At 4 h after IL-1 initiation, carboplatin was administered as a 30-min i.v. infusion at a dose of 400 mg/m(2). Treatment was repeated every 28 days. Other measured parameters included granulocyte kinetics, integrin expression on circulating WBC, and carboplatin pharmacokinetics. Of 16 patients, 11 (8 evaluable) underwent PET scanning before and at 2, 4 and 24 h after IL-1 initiation. RESULTS: Mean measured pretreatment tumor blood flow was 1.82 ml/min per g. At 2, 4 and 24 h it was 1.35, 1.67 and 1.62 ml/min per g respectively. Tumor blood flow was significantly decreased ( P<0.008) at 2 h after IL-1 initiation. In four patients, liver blood flow was measured at the same time-points as tumor blood flow. Liver blood flow was discordant with the tumor blood flow measures, showing no statistically significant change. IL-1 also caused a decreased WBC at 2 h after initiation ( n=14, P=0.025). In addition, polymorphonuclear leukocyte (PMN) and monocyte surface expression of CD11b at 2 h was increased when measured by mean fluorescence intensity flow cytometry (PMN P=0.0269, monocytes P=0.0420). No consistent effect of IL-1 on either carboplatin AUC or platelet nadir was demonstrated. CONCLUSIONS: We conclude that IL-1 has measurable effects on tumor blood flow and causes a significant decrease in blood flow as measured by PET scanning with (15)O water at 2 h after initiation. This decrease is temporally associated with a significant leukopenia and an increased expression of the adhesion integrin CD11b on the circulating cell surface (PMN and monocytes). These results suggest that IL-1 causes decreased tumor blood flow in vivo in human cancer patients, an effect that was temporally related to cytokine-induced peripheral blood cellular changes. Furthermore, our findings suggest that PET scanning may be useful to assess the effect of a systemic antineoplastic agent on tumor blood flow in cancer patients.