The DIRE score: predicting outcomes of opioid prescribing for chronic pain.

The objective of this retrospective study was to test the validity and reliability of a scoring tool (the DIRE Score), for use by clinicians, that predicts which chronic noncancer pain patients will have effective analgesia and be compliant with long-term opioid maintenance treatment. DIRE scores were assigned to 61 cases from the pain center's databases. These cases were abstracted into vignettes that were reviewed and scored by 6 physicians. Repeat scoring was carried out on a subset of 30 vignettes after 2 weeks. The main outcome measures were: global impression of compliance and efficacy as indicated in the medical record and by interview with the patient's treating clinician; and final disposition, ie, whether or not opioids were continued or discontinued at the time of last clinical documentation. Internal consistency of the factors making up the DIRE Score was high (Cronbach's alpha = .80). Sensitivity and specificity of the DIRE Score for predicting patient compliance were 94% and 87%, respectively. For efficacy, sensitivity and specificity were 81% and 76%. For disposition, the sensitivity and specificity were 86% and 73%. Intraclass correlation was 0.94 for interrater reliability and 0.95 for intrarater reliability. PERSPECTIVE: Public controversy about the use of long-term opioids for chronic pain fuels physician ambivalence about the prescribing process. In this initial retrospective study, validity and reliability of the DIRE Score are demonstrated. The score correlated well with measures of patient compliance and efficacy of long-term opioid therapy.     

Ischemic stroke after using over the counter products containing ephedra

Dietary supplements containing Ephedra used for weight loss and physical performance enhancement such as "herbal ecstasy" are widely available, and it is estimated that at least 1% of the adult population have taken these products. Ephedra products including Ephedra alkaloids such as phenylpropanolamine or other ephedrine compounds are sold under different names such as Metabolife 356, Ripped Fuel, Thermadrene, and Shape-Fast Plus. Over 2 years, five patients with ischemic infarctions associated with use of Ephedra products were evaluated at Indiana University Hospital. Ephedrine, like other sympathomimetic agents, predisposes patients to both ischemic and hemorrhagic strokes. People who take over the counter Ephedra products that claim to boost weight loss, increase energy, or bolster physical performance are at risk of adverse events including ischemic and hemorrhagic strokes.     

Cellular nonmuscle myosins NMHC‐IIA and NMHC‐IIB and vertebrate heart looping

Flectin, a protein previously described to be expressed in a left‐dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC‐II) protein class. During looping, both NMHC‐IIA and NMHC‐IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC‐IIB, rather than NMHC‐IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full‐length human NMHC‐IIA and ‐IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC‐IIB antibody does not. Abnormally looping hearts of the Nodal^{Δ 600} homozygous mouse embryos show decreased NMHC‐IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC‐II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping. Developmental Dynamics 237:3577–3590, 2008. © 2008 Wiley‐Liss, Inc.     

Molecular identification of Physaloptera sp. from wild northern bobwhite (Colinus virginianus) in the Rolling Plains ecoregion of Texas

Parasitology Research - Physaloptera spp. are common nematodes found in the stomach and muscles of mammals, reptiles, amphibians, and birds. Physaloptera spp. have a complicated life cycle with...     

Anti‐retroviral effects of type I IFN subtypes in vivo

Type I IFN play a very important role in immunity against viral infections. Murine type I IFN belongs to a multigene family including 14 IFN‐α subtypes but the biological functions of IFN‐α subtypes in retroviral infections are unknown. We have used the Friend retrovirus model to determine the anti‐viral effects of IFN‐α subtypes in vitro and in vivo. IFN‐α subtypes α1, α4, α6 or α9 suppressed Friend virus (FV) replication in vitro, but differed greatly in their anti‐viral efficacy in vivo. Treatment of FV‐infected mice with the IFN‐α subtypes α1, α4 or α9, but not α6 led to a significant reduction in viral loads. Decreased splenic viral load after IFN‐α1 treatment correlated with an expansion of activated FV‐specific CD8⁺ T cells and NK cells into the spleen, whereas in IFN‐α4‐ and ‐α9‐treated mice it exclusively correlated with the activation of NK cells. The results demonstrate the distinct anti‐retroviral effects of different IFN‐α subtypes, which may be relevant for new therapeutic approaches.     

Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype

PEX7 encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Mutations in PEX7 cause rhizomelic chondrodysplasia punctata (RCDP), a distinct peroxisome biogenesis disorder. In previous work we described three novel PEX7 mutant alleles, including one, L292X, with a high frequency due to a founder effect. We have now extended our analysis to 60 RCDP probands and identified a total of 24 PEX7 alleles, accounting for 95% of the mutant PEX7 genes in our sample. Of these, 50% are L292X, 13% are IVS9+1G>C, and the remainder are mostly private. IVS9+1G>C occurs on at least three different haplotypes and thus appears to result from recurrent mutation. The phenotypic spectrum of RCDP is broader than commonly recognized and includes minimally affected individuals at the mild end of the spectrum. To relate PEX7 genotype and phenotype, we evaluated the consequence of the disease mutation on PEX7 RNA by Northern analysis and RT/PCR. We evaluated the function of the encoded Pex7 protein (Pex7p) by expressing selected alleles in fibroblasts from RCDP patients and assaying their ability to restore import of a PTS2 marker protein. We find that residual activity of mutant Pex7p and reduced amounts of normal Pex7p are associated with milder and variant phenotypes.     

Cell-free fetal DNA and intact fetal cells in maternal blood circulation: implications for first and second trimester non-invasive prenatal diagnosis

Both intact fetal cells as well as cell-free fetal DNA are present in the maternal circulation and can be recovered for non-invasive prenatal genetic diagnosis. Although methods for enrichment and isolation of rare intact fetal cells have been challenging, diagnosis of fetal chromosomal aneuploidy including trisomy 21 in first- and second-trimester pregnancies has been achieved with a 50-75% detection rate. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. Real-time PCR assays are robust in detecting low-level fetal DNA concentrations, with sensitivity of approximately 95-100% and specificity near 100%. Comparing intact fetal cell versus cell-free fetal DNA methods for non-invasive prenatal screening for fetal chromosomal aneuploidy reveals that the latter is at least four times more sensitive. These preliminary results do not support a relationship between frequency of intact fetal cells and concentration of cell-free fetal DNA. The above results imply that the concentration of fetal DNA in maternal plasma may not be dependent on circulating intact fetal cells but rather be a product of growth and cellular turnover during embryonic or fetal development.     

Postpartum intrauterine device contraception: A review

AIM: To review the safety (infection, perforation) and efficacy (expulsion, continuation rates, pregnancy) of intrauterine device (IUD) insertion in the postpartum period. METHODS: MEDLINE, PubMed and Google Scholar were searched for randomized controlled trials and prospective cohort studies of IUD insertions at different times during the postpartum period. Time of insertion during the postpartum period was documented specifically, immediate post placenta period (within 10 min), early post placenta period (10 min to 72 h), and delayed/interval period (greater than 6 wk). Other study variables included mode of delivery, vaginal vs cesarean, manual vs use of ring forceps to insert the IUD. RESULTS: IUD insertion in the immediate postpartum (within 10 min of placental delivery), early postpartum (10 min up to 72 h) and Interval/Delayed (6 wk onward) were found to be safe and efficacious. Expulsion rates were found to be highest in the immediate postpartum groups ranging from 14% to 27%. Immediate post placental insertion found to have expulsion rates that ranged from 3.6% to 16.2%. Expulsion rate was significantly higher after insertion following vaginal vs cesarean delivery. The rates of infection, perforation and unplanned pregnancy following postpartum IUD insertion are low. Method of insertion such as with ring forceps, by hand, or another placement method unique to the type of IUD did not show any significant difference in expulsion rates. Uterine perforations are highest in the delayed/interval IUD insertion groups.Breastfeeding duration and infant development are not affected by delayed/interval insertion of the non-hormonal (copper) IUD or the Levonorgestrel IUD. Timing of the Levonorgestrel IUD insertion may affect breastfeeding. CONCLUSION: IUD insertion is safe and efficacious during the immediate postpartum, early postpartum and delayed postpartum periods. Expulsion rates are highest after vaginal delivery and when inserted during the immediate postpartum period. IUD associated infection rates were not increased by insertion during the postpartum period over interval insertion rates. There is no evidence that breastfeeding is negatively affected by postpartum insertion of copper or hormone-secreting IUD. Although perforation rates were higher when inserted after lactation was initiated. Randomized controlled trials are needed to further elucidate the consequence of lactation on postpartum insertion. Despite the concerns regarding expulsion, perforation and breastfeeding, current evidence indicates that a favorable risk benefit ratio in support of postpartum IUD insertion. This may be particularly relevant for women for whom barriers exist in achieving desired pregnancy spacing.     

Phenotypic and functional properties of murine {gamma}{delta} T cell clones derived from malaria immunized, {alpha}{beta} T cell-deficient mice

Six murine T cell clones expressing TCR were generated frommalaria immunized, ß T celldeficient mice. Phenotypiccharacterization of these clones has revealed that, in contrastto conventional ß T cells, there is a considerabledegree of heterogeneity among these clones with regard to theirsurface markers and their lymphokine profile. One clone wasfound to display significant anti-parasite activity in vivoupon adoptive transfer. We attempted to determine whether theprotective clone differs in one or more key characteristicsfrom the non-protective clones. Although no obvious patternpeculiar to the protective clone was observed, it appears thatmore than one parameter may, in combination, define a distinctprotective phenotype, and thus explain the functional differencebetween the protective and non-protective clones.     

Effect of <Emphasis Type="Italic">Myracrodruon urundeuva</Emphasis> leaf lectin on survival and digestive enzymes of <Emphasis Type="Italic">Aedes aegypti</Emphasis> larvae

Aedes aegypti transmits the viruses that cause yellow and dengue fevers. Vector control is essential, since a vaccine for dengue has not as yet been made available. This work reports on the larvicidal activity of Myracrodruon urundeuva leaf lectin (MuLL) against A. aegypti fourth-stage larvae (L₄). Also, the resistance of MuLL to digestion by L₄ gut proteases and the effects of MuLL on protease, trypsin-like and α-amylase activities from L₄ gut were evaluated to determine if lectin remains active in A. aegypti gut and if insect enzyme activities can be modulated by MuLL. MuLL promoted mortality of L₄ with LC₅₀ of 0.202 mg/ml. Haemagglutinating activity of MuLL was detected even after incubation for 96 h with L₄ gut preparation containing protease activity. MuLL affected the activity of gut enzymes, inhibiting protease and trypsin activities and stimulating α-amylase activity. The results suggest that MuLL may become a new biodegradable larvicidal agent for dengue control. Larvicidal activity of MuLL may be linked to its resistance to proteolysis by larval enzymes and interference in the activity of digestive larval enzymes.