Day-case diagnostic and interventional peripheral angiography: 10-year experience in a radiology specialist nurse-led unit.

We describe a prospective evaluation of the safety of peripheral angiography procedures performed on day-case patients in a dedicated radiological nurse-led and administrated unit. Patients referred for peripheral vascular angiography, over a 10-year period, were pre-assessed by a radiology specialist nurse in a nurse-led clinic. Radiologists performed all procedures, whereas radiology specialist nurses were responsible for patient care before, during and after angiography and during the 24 h follow-up. Procedures were divided into diagnostic or interventional; complications were divided into immediate or delayed (24 h follow-up) either requiring hospital admission (major) or day-case unit management (minor). Patient acceptability was assessed using a standard questionnaire. Cost analysis was also performed. 401 day-case peripheral angiography procedures (144 diagnostic and 257 interventional) were performed in 310 patients. 109/401 (27.2%) procedures were performed on patients with diabetes mellitus. In diagnostic studies, 16/144 (11.1%) immediate and 6/144 (4.2%) delayed complications occurred whereas, in interventional studies, 65/257 (25.3%) immediate and 13/257 (5.1%) delayed complications were noted. A major complication occurred in 17/257 (6.6%) of patients in the interventional group and 3/144 (2.1%) in the diagnostic group. Puncture site haematoma was the most common complication. Nurse-led care was acceptable to the patient, with a high level of patient satisfaction seen. In conclusion, day-case diagnostic and interventional peripheral angiography procedures can be performed safely in a specialist nurse-led and administrated unit, with complication rates being within the accepted guidelines.

Gastrointestinal side effects in chronic opioid users: results from a population-based survey.

BACKGROUND: Gastrointestinal side effects are commonly associated with opioid treatment for pain. AIM: To understand gastrointestinal side effects associated with opioid treatment. METHODS: This study was a population-based survey of adults in the US who use opioids to manage pain unrelated to cancer. Participants were recruited from an existing Web-enabled panel and a supplemental panel of individuals who previously indicated an interest in participating in Web-based surveys. RESULTS: Overall, 2055 individuals participated in the main phase of the survey. Fifty-seven per cent of participants reported having had constipation that they associated with opioid treatment, and 49% reported constipation in the previous 4 weeks. Thirty-six per cent of participants reported new or worsening constipation in the previous 4 weeks. Thirty-three per cent of participants reported constipation as their most bothersome symptom associated with opioid treatment, 13% reported nausea, 11% abdominal pain and 10% gas. Seventy-three per cent of the participants who reported any GI symptoms did not change the dosage level or frequency of use of opioids because of adverse events, which may be explained by the fact that 72% of participants used over-the-counter laxatives and 12% a prescription laxative. CONCLUSION: Constipation is a frequent and significant event occurring with opioid use.

Development of educational image databases and e-books for medical physics training.

Medical physics education and training requires the use of extensive imaging material and specific explanations. These requirements provide an excellent background for application of e-Learning. The EU projects Consortia EMERALD and EMIT developed five volumes of such materials, now used in 65 countries. EMERALD developed e-Learning materials in three areas of medical physics (X-ray diagnostic radiology, nuclear medicine and radiotherapy). EMIT developed e-Learning materials in two further areas: ultrasound and magnetic resonance imaging. This paper describes the development of these e-Learning materials (consisting of e-books and educational image databases). The e-books include tasks helping studying of various equipment and methods. The text of these PDF e-books is hyperlinked with respective images. The e-books are used through the readers' own Internet browser. Each Image Database (IDB) includes a browser, which displays hundreds of images of equipment, block diagrams and graphs, image quality examples, artefacts, etc. Both the e-books and IDB are engraved on five separate CD-ROMs. Demo of these materials can be taken from www.emerald2.net.

A mutant of eukaryotic protein synthesis initiation factor eIF4E(K119A) has an increased binding affinity for both m7G cap analogues and eIF4G peptides.

The eukaryotic multisubunit initiation factor eIF4F is an essential component of the translational machinery. Recognition of the cap structure of mRNA, m(7)GpppN, where N is any nucleotide, by eIF4E is required for initiation of translation. Here we compare the equilibrium and thermodynamic binding characteristics of wild-type eIF4E and a high-affinity mutant, eIF4E(K119A), with those of cap analogues and eIF4G peptides. The temperature-dependent K(d) values for cap analogues were markedly lower, indicating tighter binding, with the eIF4E(K119A) mutant compared with wild-type eIF4E. Although interactions with cap analogues were found to be enthalpically driven, entropic contributions were also significant. Moreover, the binding affinities of eIF4G peptides were 2-4-fold tighter for eIF4E(K119A) than for eIF4E(wt). These results demonstrate that the binding affinity for both the mRNA cap and eIF4G peptides can be simultaneously altered by point mutations distant from either binding site. Entropic contributions to binding suggesting hydrophobic interactions are larger in the mutant protein and are most likely due to a conformational change.

Environmental benefits and economic costs of manure incorporation on dairy waste application fields.

Model simulations performed representing dairies in a 93000 ha watershed in north central Texas suggest that manure incorporation results in reduced phosphorus (P) losses at relatively small to moderate cost to producers. Simulated manure incorporation with a tandem disk on fields double-cropped with sorghum/winter wheat resulted in up to 33, 45, and 37% reductions in per hectare sediment-bound, soluble, and total P losses in edge-of-field runoff, relative to simulated surface manure applications. The effects of incorporation were evaluated at three different manure application rates. On aggregate across all three manure application rates, significant declines in P losses were obtained with incorporation except for sediment-bound P losses under the N-based manure application rate scenario. We found that the practice of incorporating manure shortly after it has been broadcast on the soil surface could help reduce P losses in such situations where P-based rates alone prove inadequate. The cost the producer incurs when manure is incorporated is on average about 1% of net returns when manure is applied at the N rate and 2-3% when it is applied at alternative P-based rates. In practice the costs could be lower because producers may substitute the manure incorporation operation for a tandem disk operation performed prior to manure application. As more and more dairy producers switch to the use of sorghum and corn silage in dairy rations and consequent on-farm production of these forages, the practice of manure incorporation may help to reduce phosphorus losses resulting from dairy manure applications to fields with these forage crops.

Homeostasis in mRNA initiation: wheat germ poly(A)-binding protein lowers the activation energy barrier to initiation complex formation.

Previous kinetic binding studies of wheat germ protein synthesis eukaryotic initiation factor iso4F (eIFiso4F) and its subunit, eIF4E, with m(7)GTP and mRNA analogues indicated that binding occurred by a two-step process with the first step being too fast to measure by stopped-flow techniques (). Further equilibrium studies showed that poly(A)-binding protein (PABP) enhanced the cap binding of eIFiso4F about 40-fold. The kinetic effects of PABP on cap binding and the temperature dependence of this reaction were measured and compared. Fluorescence stopped-flow studies of the PABP.eIFiso4F protein complex with cap show a concentration-independent conformational change. PABP did not significantly increase the rate of the conformational change, and because the initial second-order binding is essentially diffusion-controlled, the enhancement of cap affinity must reside in the dissociation rate. The dissociation rate was more than 5-fold slower in the presence of PABP. The temperature dependence of the cap binding reaction was markedly reduced in the presence of PABP. The reduced energy barrier for formation of a cap.eIFiso4F complex suggests a more stable platform for further initiation complex formation and a possible means of adapting to varying temperature conditions.

Distraction-flexion injury in a neurologically intact pediatric patient treated nonoperatively: case study.

STUDY DESIGN: A case study was conducted. OBJECTIVE: To detail the successful nonoperative management of a distraction-flexion Salter-Harris Type 1 midcervical spine injury in a young child. SUMMARY OF BACKGROUND DATA: Documented cases of neurologically intact pediatric patients with unstable flexion-distraction injuries of the midcervical spine are rare. METHODS: A case report and literature review are presented. RESULTS: A rare distraction-flexion injury was successfully treated nonoperatively. CONCLUSIONS: Although distraction-flexion cervical spine injuries are common in adults and often occur with concomitant neurologic sequelae, they also can occur in the pediatric patient. Whereas these injuries require surgery in adults, they can be managed nonoperatively in the pediatric population.

Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice.

Mutations at the waltzer (v) locus result in deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear. Here, we use a positional cloning approach to show that waltzer encodes a novel cadherin (Cdh23), which is most closely related to the Drosophila Fat protein. A single nucleotide deletion in the v(J) allele and a single nucleotide insertion in the v allele are predicted to truncate each protein near the N-terminus and produce a functional null allele. In situ hybridization analysis showed that Cdh23 is expressed in the sensory hair cells of the inner ear, where it has been suggested to be a molecule critical for crosslinking of the stereocilia. In addition, Cdh23 is expressed in the urticulo-saccular foramen,the ductus reuniens, and Reissner's membrane, suggesting that Cdh23 may also be involved in maintaining the ionic composition of the endolymph. Finally, mutations in human CDH23 have recently been described for two loci, DFNB12 and USH1D, which cause nonsyndromic deafness, identifying waltzer as a mouse model for human hearing loss.

Reliability of rotary prism fusional vergence ranges.

BACKGROUND: The measurement of fusional vergence ranges is an important clinical test in the assessment of binocular vision status. Fusional vergence ranges are typically measured by recording a patient's reports of blur, break, and recovery to base-in (BI) and base-out (BO) prism. Published reliability data on fusional vergence ranges are very limited. METHODS: Eight subjects underwent four testing sessions, at which repeated measurements of fusional vergence ranges were taken. Near ranges were tested at the first session only Distance ranges were tested at all four sessions. Intra-examiner standard deviations were calculated for each fusional vergence test result (BI and BO; blur, break, and recovery) for each session. Intra-examiner standard deviations were averaged. These values were used to determine 95% limits of agreement. RESULTS: The 95% limits of agreement were between 2 delta and 2.5 delta for the distance BI break and recovery and for the near BI recovery; between 3 and 4 delta for near BI break and near BO break; between 4 and 5 delta for distance BO blur and recovery and for near BI blur; and between 5 and 5.5 delta for distance BO break and near BO blur and recovery.

Kinetic proofreading scanning models for eukaryotic translational initiation: the cap and poly(A) tail dependency of translation.

Two simplified kinetic proofreading scanning (KPS) models were proposed to describe the 5' cap and 3' poly(A) tail dependency of eukaryotic translation initiation. In Model I, the initiation factor complex starts scanning and unwinding the secondary structure of the 5' untranslated region (UTR) from the 5' terminus of mRNA. In Model II, the initiation factor complex starts scanning from any binding site in the 5' UTR. In both models, following ATP hydrolysis, the initiation factor complex either dissociates from mRNA or continues to scan and unwind RNA secondary structure in the 5' UTR. This step repeats n times until the AUG codon is reached. These two models show very different cap and/or poly(A) tail dependency of translation initiation. The models predict that both cap and poly(A) tail dependencies of translation, and translatability of mRNAs are coupled with the structure of 5' UTR: the translation of mRNA with structured 5' UTR is strongly cap- and poly(A) tail-dependent; while translation of mRNA with unstructured 5' UTR is less cap- and poly(A) tail-dependent. We use these two models to explain: (1) the cap and poly(A) tail dependence of translation; (2) the effect of exogenous poly(A) on translation; (3) repression of host mRNA and translation of late adenovirus mRNA in the late phase of adenovirus infection; (4) repression of host mRNA and translation of Vaccinia virus mRNA in virus-infected cell; (5) heat shock repression of translation of normal mRNA and stimulation of translation of hsp mRNA; and (6) the synergistic effect of cap and poly(A) tail on stimulating translation. The kinetic proofreading scanning models provide a coherent interpretation of those phenomena.

Wheat germ translation initiation factor eIF4B affects eIF4A and eIFiso4F helicase activity by increasing the ATP binding affinity of eIF4A.

It has been proposed that, during translational initiation, structures in the 5' untranslated region of mRNA are unwound. eIF4A, a member of the DEAD box family of proteins (those that contain a DEAD amino acid sequence), separately or in conjunction with other eukaryotic initiation factors, utilizes the energy from ATP hydrolysis to unwind these structures. As a step in defining the mechanism of helicase activity in the wheat germ protein synthesis system, we have utilized direct fluorescence measurements, ATPase assays, and helicase assays. The RNA duplex unwinding activity of wheat germ eIF4A is similar to other mammalian systems; however, eIF4F or eIFiso4F is required, probably because of the low binding affinity of wheat germ eIF4A for mRNA. Direct ATP binding measurements showed that eIF4A had a higher binding affinity for ADP than ATP, resulting in a limited hydrolysis and procession along the RNA in the helicase assay. The addition of eIF4B resulted in a change in binding affinity for ATP, increasing it almost 10-fold while the ADP binding affinity was approximately the same. The data presented in this paper suggest that eIF4F or eIFiso4F acts to position the eIF4A and stabilize the interaction with mRNA. ATP produces a conformational change which allows a limited unwinding of the RNA duplex. The binding of eIF4B either prior to or after hydrolysis allows for increased affinity for ATP and for the cycle of conformational changes to proceed, resulting in further unwinding and processive movement along the mRNA.

Wheat germ poly(A)-binding protein increases the ATPase and the RNA helicase activity of translation initiation factors eIF4A, eIF4B, and eIF-iso4F.

Recent studies demonstrated that wheat germ poly(A)-binding protein (PABP) interacted with translation eukaryotic initiation factor (eIF)-iso4G and eIF4B, and these interactions increased the poly(A) binding activity of PABP (Le, H., Tanguay, R. L., Balasta, M. L., Wei, C. C., Browning, K. S., Metz, A. M., Goss, D. J., and Gallie, D. R. (1997) J. Biol. Chem. 272, 16247-16255) and the cap binding activity of eIF-iso4F (Wei, C. C., Balasta, M. L., Ren, J., and Goss, D. J. (1998) Biochemistry 37, 1910-1916). We report here that the interaction between PABP and eIF-iso4G has a substantial effect on the ATPase activity and RNA helicase activity of (eIF4A + eIF4B + eIF-iso4F) complex. ATPase kinetic assays show, in the presence of poly(U), PABP can increase the parameter (k(cat)/K(m)) by 3.5-fold with a 2-fold decrease of K(m) for the (eIF4A + eIF-iso4F) complex. In the presence of globin messenger RNA, the ATPase activity of the complex (eIF4A + eIF-iso4F) was increased 2-fold by the presence of PABP. RNA helicase assays demonstrated that the presence of PABP enhanced the RNA duplex unwinding activity of the initiation factor complex. These results suggest that, in terms of the scanning model of translation initiation, PABP may enhance the mRNA scanning rate of the complex formed by eIF4A, eIF4B, and eIF4F or eIF-(iso)4F and increase the rate of translation.

Deletion of Dad1 in mice induces an apoptosis-associated embryonic death.

Dad1 is a putative anti-apoptosis gene identified in several distantly related organisms. Expression of Dad1 in transfected cells inhibits apoptosis in vitro. To determine whether Dad1 has a similar function in vivo, we used gene targeting to delete Dad1. Heterozygous adult mice (+/-) show no obvious phenotype or abnormalities, but genotype analysis of over 100 offspring from heterozygous matings detected no weanling, homozygous Dad1 null (-/-) mice. Subsequent analysis of embryos from heterozygous matings detected Dad1 null (-/-) embryos at E3.5 but no later, suggesting Dad1 is required for development beyond the late blastocyst stage. Increased levels of apoptosis were observed in cultured embryos lacking a functional copy of the gene, consistent with an anti-apoptotic role for Dad1.

Absence of the tight junctional protein AF-6 disrupts epithelial cell-cell junctions and cell polarity during mouse development.

BACKGROUND: The establishment, maintenance and rearrangement of junctions between epithelial cells are extremely important in many developmental, physiological and pathological processes. AF-6 is a putative Ras effector; it is also a component of tight and adherens junctions, and has been shown to bind both Ras and the tight-junction protein ZO-1. In the mouse, AF-6 is encoded by the Af6 gene. As cell-cell junctions are important in morphogenesis, we generated a null mutation in the murine Af6 locus to test the hypothesis that lack of AF-6 function would cause epithelial abnormalities. RESULTS: Although cell-cell junctions are thought to be important in early embryogenesis, homozygous mutant embryos were morphologically indistinguishable from wild-type embryos through 6.5 days post coitum (dpc) and were able to establish all three germ layers. The earliest morphological abnormalities were observed in the embryonic ectoderm of mutant embryos at 7.5 dpc. The length of the most apical cell-cell junctions was reduced, and basolateral surfaces of those cells were separated by multiple gaps. Cells of the embryonic ectoderm were less polarized as assessed by histological criteria and lateral localization of an apical marker. Mutant embryos died by 10 dpc, probably as a result of placental failure. CONCLUSIONS: AF-6 is a critical regulator of cell-cell junctions during mouse development. The loss of neuroepithelial polarity in mutants is consistent with a loss of efficacy of the cell-cell junctions that have a critical role in establishing apical/basolateral asymmetry.

Clinical findings before the onset of myopia in youth: 5. Intraocular pressure.

BACKGROUND: We conducted a study to compare variables in children who were initially emmetropic and subsequently became myopic to those in children who remained emmetropic. This paper investigates intraocular pressure (IOP) in the two groups. Some theories of myopia development suggest a role for elevated IOP in axial elongation of the eye, and some studies have found higher IOPs in myopes than in nonmyopes. METHODS: A cohort of initially emmetropic children were given eye and vision examinations at 6-month intervals over a 3-year period. IOPs were obtained by Goldmann tonometry. RESULTS: The mean IOP for the became-myopic group was 13.9 mm Hg (N = 24; SD = 2.5). The mean IOP for the remained-emmetropic group was 14.7 mm Hg (N = 53; SD = 3.1). The difference was not statistically significant. CONCLUSION: Children who became myopic did not show a greater IOP at an examination 6 months or less before the onset of myopia than children who remained emmetropic.

Relationship of accommodative response and nearpoint phoria in a sample of myopic children.

Esophoria has been associated with onset and progression of myopia in children. The induction of myopia by optical defocus shown by animal models suggests that a high lag of accommodation during near work may contribute to myopia in children. This paper examines the relationship of nearpoint phoria and accommodative response in a sample of children with myopia. Accommodative response was measured under binocular conditions with the Canon Autoref R-1 autorefractor with a 40 cm viewing distance. Phorias were measured with the von Graefe method using a 40 cm test distance. In the statistical analysis exophoria was scored as a negative number and esophoria was scored as a positive number. The coefficient of correlation of accommodative response with phoria was -0.32 (n = 73; p<0.01), thus showing an association of a more positive (more convergent) near phoria with lower accommodative response. The correlation coefficient increased to -0.39 when an exponential function was used. When only esophores were considered, the correlation coefficient was -0.59 (n = 44; p<0.001). Lower accommodative response (higher lag of accommodation) was associated with greater esophoria.

Refractive error changes in mixed astigmatism.

The purpose of this note is to examine refractive error changes in children who change from mixed astigmatism to myopic astigmatism. Data were collected for 16 children who changed from mixed astigmatism to simple myopic or compound myopic astigmatism. Children with mixed astigmatism showed minimal refractive changes until they converted to myopic astigmatism, at which time refractive changes increased.