bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of phenobarbitone N‐glucosidation by valproate.
Authors: Bernus I , Dickinson RG , Hooper WD , Eadie MJ
Published: July 2012

Plasma phenobarbitone concentrations and daily urinary excretion of phenobarbitone and its metabolites p‐hydroxyphenobarbitone (conjugated and unconjugated), and [S]‐phenobarbitone‐N‐glucoside were measured under steady‐state conditions in two groups of epileptic patients, (i) taking phenobarbitone with or without other drugs, but not valproate (n = 12), and (ii) taking phenobarbitone with other drugs including valproate (n = 8). Mean steady‐state plasma phenobarbitone concentrations were 5.9 mg l‐1 higher, relative to drug dose, in the patients taking valproate than in those not taking valproate. Urinary excretion of [S]‐phenobarbitone‐N‐glucoside was significantly lower in the group taking valproate (1.9 +/‐ s.d. 2.0% of phenobarbitone dose vs 16.2 +/‐ s.d. 9.9%). Urinary excretion of phenobarbitone (23.7 +/‐ s.d. 9.8% vs 48.2 +/‐ s.d. 13.6%) and unconjugated p‐hydroxyphenobarbitone (5.7 +/‐ s.d. 3.9% vs 16.0 +/‐ s.d. 9.1%) was higher in those taking valproate, while conjugated p‐hydroxyphenobarbitone excretion was similar in both groups (8.3 +/‐ s.d. 4.9% vs 6.5 +/‐ s.d. 2.9%). Valproate appeared to inhibit both the direct N‐glucosidation of phenobarbitone and the O‐glucuronidation of p‐hydroxyphenobarbitone.
Pharmacokinetics and biochemical efficacy of idrapril calcium, a novel ACE inhibitor, after multiple oral administration in humans.
Authors: Wyld PJ , Grant J , Lippi A , Criscuoli M , Del Re G , Subissi A
Published: July 2012

The pharmacokinetic profile and biochemical efficacy of idrapril calcium, a novel angiotensin converting enzyme (ACE) inhibitor, were evaluated in healthy volunteers after multiple dosing for 5 days at the doses of 100, 200 and 400 mg twice daily. The study was conducted as a double‐blind, cross‐over comparison of idrapril calcium against placebo. Plasma concentrations of idrapril were determined by an indirect enzymatic method. Urinary concentrations were measured by reverse phase high performance liquid chromatography (h.p.l.c.). Plasma samples were also analysed for ACE activity. The pharmacokinetics of idrapril calcium did not change significantly between day 1 and day 5. The values of Cmax and AUC were dose‐related over the range of doses tested; tmax was 3‐4 h and apparent elimination half‐life was 1.4‐1.6 h. Plasma ACE activity was maximally inhibited (94‐96%) at all dose levels and remained more than 80% depressed from 2 to at least 6 h after idrapril calcium. Although the maximum effect was not dose‐ related, the duration of inhibition showed some dose‐dependency, ACE activity returning to 56, 45 and 29% of the basal value 12 h after the 100, 200 and 400 mg doses, respectively. There were no clinically significant adverse events experienced by the volunteers. No dose‐ related effects on blood pressure or heart rate were observed. There were no changes in clinical pathology tests, urine analyses or electrocardiograms after dosing with idrapril calcium. Idrapril calcium, the prototype of a new class of ACE inhibitors, appears to be well‐tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Population pharmacokinetics of nortriptyline during monotherapy and during concomitant treatment with drugs that inhibit CYP2D6‐an evaluation with the nonparametric maximum likelihood method.
Authors: Jerling M , Merle Y , Mentre F , Mallet A
Published: July 2012

Therapeutic drug monitoring data for nortriptyline (674 analyses from 578 patients) were evaluated with the nonparametric maximum likelihood (NPML) method in order to determine the population kinetic parameters of this drug and their relation to age, body weight and duration of treatment. Clearance of nortriptyline during monotherapy exhibited a large interindividual variability and a skewed distribution. A small, separate fraction with a very high clearance, constituting between 0.5% and 2% of the population, was seen in both men and women. This may be explained by the recent discovery of subjects with multiple copies of the gene encoding the cytochrome‐P450‐enzyme CYP2D6, which catalyses the hydroxylation of nortriptyline. However, erratic compliance with the prescription may also add to this finding. A separate distribution of low clearance values with a frequency corresponding to that of poor metabolizers of CYP2D6 (circa 7% in Caucasian populations) could not be detected. Concomitant therapy with drugs that inhibit CYP2D6 resulted in a major increase in the plasma nortriptyline concentrations. This was caused by a decrease in nortriptyline clearance, whereas the volume of distribution was unchanged. The demographic factors age and body weight had a minor influence on the clearance of nortriptyline which was also unaffected by the duration of treatment.
Reproducibility and consistency of the responses to supine bicycle ergometry; evaluation in conjunction with beta 1‐adrenoceptor occupancies.
Authors: de Mey C , Breithaupt‐Grogler K , Schloos J , Palm D , Belz GG
Published: July 2012

A protocol is presented for supine bicycle ergometry in healthy subjects, which aims for a target increase of heart rate (HR = 140 beats min‐1) after 4 min cycling under constant load. The required load is selected from a pre‐study ergometry with stepwise increasing load. Repeated testing with this protocol was shown to yield highly reproducible ergometric HR‐responses. Because of their high reliability, the ergometric endpoints and increments permit a highly sensitive comparison of beta 1‐adrenoceptor antagonism across dose and time within a given compound. The relationship between the changes of the ergometric rise of HR and the beta 1‐adrenoceptor occupancy (estimated from radioreceptor assay data) permits to evaluate the ergometric efficiency of different beta‐adrenoceptor antagonists across time and doses and to identify eventual differences that do not relate primarily to the extent of beta 1‐adrenoceptor antagonism itself.
Pravastatin inhibits cellular cholesterol synthesis and increases low density lipoprotein receptor activity in macrophages: in vitro and in vivo studies.
Authors: Keidar S , Aviram M , Maor I , Oiknine J , Brook JG
Published: July 2012

1. Pravastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme‐A (HMG‐CoA) inhibitor, is a highly selective inhibitor of hepatic cholesterol synthesis. We studied the in vivo and in vitro effects of pravastatin on macrophage cholesterol metabolism. 2. The effects of incubating pravastatin with human monocyte derived macrophages (HMDM), mouse peritoneal macrophages (MPM) and a J‐774 A.1 macrophage‐like cell line, on macrophage cholesterol synthesis, cellular degradation of native low density lipoprotein (LDL) and modified LDL, cholesterol efflux from these cells and the cholesterol esterification rate were determined. 3. Pravastatin was administered either as one 40 mg dose or 40 mg daily for 8 weeks to normocholesterolaemic and hypercholesterolaemic individuals. The effects on cholesterol synthesis and degradation in monocytes derived from these subjects were studied. 4. In vitro, pravastatin resulted in a dose‐dependent inhibition of macrophage cholesterol synthesis. Cellular degradation of native LDL increased by 119% in the presence of 0.1 mg ml‐1 pravastatin. Degradation of both acetyl LDL and oxidized LDL was unaffected. Small concentrations of pravastatin (up to 0.19 micrograms ml‐1) increased the cellular cholesterol esterification rate after incubation with LDL, but higher concentrations resulted in an inhibition of the esterification. 5. Single dose pravastatin administration caused a reduction in cholesterol synthesis by the subjects own HMDM by 62% and 47% in normocholesterolaemic and hypercholesterolaemic individuals, respectively. Chronic administration resulted in a 55% inhibition of cholesterol synthesis and a 57% increase in LDL degradation. 6. The results indicate that the selective uptake of pravastatin shown for hepatocytes can be extended to macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)
In vitro proguanil activation to cycloguanil by human liver microsomes is mediated by CYP3A isoforms as well as by S‐mephenytoin hydroxylase.
Authors: Birkett DJ , Rees D. , Andersson T. , Gonzalez FJ , Miners JO , Veronese ME
Published: July 2012

1. The activation of proguanil to cycloguanil by human liver microsomes was studied to define the cytochrome P450 (CYP) isoforms involved in this reaction. 2. Apparent Km values for proguanil ranged from 35 microM to 183 microM with microsomes from four human livers. 3. There was a 6.3‐fold range of activity with microsomes from seventeen human livers. Rates of proguanil activation correlated significantly with CYP3A activities (benzo[a]pyrene metabolism, caffeine 8‐oxidation and omeprazole sulphone formation) and CYP3A immunoreactive content. There was also a highly significant correlation with rates of hydroxyomeprazole formation. Correlations with activities selective for CYP1A2, CYP2C9/10 and CYP2E1, and with immunoreactive CYP1A2 content were not significant. 4. Proguanil activation was inhibited by R,S‐ mephenytoin, troleandomycin and by inhibitory anti‐CYP3A antiserum and anti‐CYP2C IgG and was activated by alpha‐naphthoflavone. Inhibitors selective for CYP1A2, CYP2E1, CYP2A6 or CYP2C9/10 had little or no effect on proguanil activation. The extents of inhibition by R,S‐ mephenytoin, troleandomycin and the two antibodies varied with the immunoreactive CYP3A content of the microsomes used. 5. It is concluded that proguanil activation to cycloguanil by human liver microsomes is mediated both by S‐mephenytoin hydroxylase and isoforms of the CYP3A subfamily. This has implications for the use of proguanil as an in vivo probe for the S‐mephenytoin poor metaboliser phenotype.
Lack of tolerance in forearm blood vessels in man to glyceryl trinitrate.
Authors: Cheesman AR , Benjamin N.
Published: July 2012

1. Nitrate tolerance is a clinical problem. The cause is not known but it has been suggested that tolerance to organic nitrates occurs within the blood vessels to reduce sensitivity to the drug. We have determined the sensitivity of human forearm resistance vessels and veins to glyceryl trinitrate (GTN) at the beginning and end of a 7 day period of GTN administration in healthy volunteers using a clinically relevant dose of transdermal drug. 2. Eight healthy volunteers completed the study which entailed measurement of change in forearm venous compliance and change in forearm blood flow following intraarterial infusions of two doses of glyceryl trinitrate (0.5 and 2.0 micrograms min‐1) before, after 2 h and after 7 days of transdermal GTN administration using one 10 mg patch each 24 h. 3. Changes in venous compliance and blood flow were measured by venous occlusion plethysmography using a basal infusion of noradrenaline (1 microgram min‐1) to increase venous tone. 4. Noradrenaline produced the expected decrease in forearm blood flow and venous compliance. The effect of locally infused GTN on venous compliance and forearm blood flow was similar on the three study days. In particular there was no significant difference in the response to GTN following 7 days transdermal administration compared with that after 2 h. 5. We conclude from this study that local vascular tolerance to GTN is unlikely to explain the clinical problem of nitrate tolerance, and that other mechanisms such as neurohumoral activation may be important.
Patterns of subsequent malignancies after Hodgkin lymphoma in children and adults
Authors: Omer Bilal , Kadan‐Lottick Nina S. , Roberts Kenneth B. , Wang Rong , Demsky Carolyn , Kupfer Gary M. , Cooper Dennis , Seropian Stuart , Ma Xiaomei
Published: July 2012

To evaluate the impact of reduced radiation and combined modality therapy (CMT) in the treatment of Hodgkin lymphoma, we assessed the risk of second malignant neoplasms (SMNs) in patients who received extended‐field radiotherapy only and patients who underwent CMT. Among 404 patients treated at Yale during 1970–2004, the risk of solid SMNs was elevated in the radiotherapy only group (n = 198, median follow‐up = 21·1 years) compared to the general population, with a standardized incidence ratio (SIR) of 1·85 [95% confidence interval (CI): 1·17–2·78]. No increase was observed in the CMT group (n = 206, median follow‐up = 14·3 years), although potential differences in SMN risk were indicated across the age spectrum in subgroup analysis. Patients who received mustard‐containing regimens had increased risks for haematological SMNs (SIR = 8·74) and all SMNs (SIR = 1·85). When the analysis was stratified by age at diagnosis, children (0–20 years) had a significantly higher risk of SMNs (SIR = 5·24, 95% CI: 2·26–10·33), regardless of the treatment received. These findings suggest that recent treatment options utilizing lower dose radiation and less intense alkylator chemotherapy might be associated with lower incidences of SMNs among adults but not necessarily children.
Interleukin‐25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL‐17RB, but not IL‐17RA
Authors: Wang W. , Fan Y. Q. , Lv Z. , Yao X. J. , Wang W. , Huang K. W. , Meng Q. , Fang C. L. , Lee T. H. , Corrigan C. J. , An Y. Q. , Ying S.
Published: July 2012

Background

Unlike other IL‐17 family members, the Th2‐derived cytokine IL‐25 (IL‐17E) induces (promotes) Th2 responses. One or both of the two receptors for IL‐25 (IL‐17RA, IL‐17RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2‐type inflammation IL‐25 may also act on structural cells at sites of Th2‐type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes.

Objective

Our previous studies showed elevated expression of IL‐25 and IL‐17RB immunoreactivity in asthmatic airways with co‐localization of the latter to endothelial cells. We therefore hypothesized that IL‐25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor (bFGF).

Methods

Polymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL‐17RB, IL‐17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL‐25 and bFGF in asthmatic bronchial biopsies. Receptor‐blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL‐25 acts on IL‐17RB or IL‐17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL‐25‐mediated bFGF expression.

Results

HUVEC constitutively expressed IL‐17RB, IL‐17RA and bFGF. Production of the latter was further increased by IL‐25, but attenuated after blockade of the IL‐17RB, but not the IL‐17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL‐25‐induced angiogenesis which was also inhibited by blocking IL‐17RB, but not IL‐17RA. The PI3K‐specific inhibitor LY294002 also completely attenuated IL‐25‐induced bFGF expression. Immunoreactivity for IL‐25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other.

Conclusions and Clinical Relevance

Our data support the hypothesis that IL‐25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL‐17RB receptor through PI3K‐signalling pathways. Targeting the pathways might benefit therapy of airways remodelling.
Immune responses against islet allografts during tapering of immunosuppression – a pilot study in 5 subjects
Authors: Huurman V A L , van der Torren C R , Gillard P , Hilbrands R , van der Meer-Prins E P M W , Duinkerken G , Gorus F K , Claas F H J , Keymeulen B , Roelen D L , Pipeleers D G , Roep B O
Published: July 2012

Transplantation of isolated islet of Langerhans cells has great potential as a cure for type 1 diabetes but continuous immune suppressive therapy often causes considerable side effects. Tapering of immunosuppression in successfully transplanted patients would lower patients' health risk. To identify immune biomarkers that may prove informative in monitoring tapering, we studied the effect of tapering on islet auto- and alloimmune reactivity in a pilot study in five transplant recipients in vitro. Cytokine responses to the graft were measured using Luminex technology. Avidity of alloreactive cytotoxic T Lymphocytes (CTL) was determined by CD8 blockade. The influence of immunosuppression was mimicked by in vitro replenishment of tacrolimus and MPA, the active metabolite of mycophenolate mofetil. Tapering of tacrolimus was generally followed by decreased C-peptide production. T-cell autoreactivity increased in four out of five patients during tapering. Overall alloreactive CTL precursor frequencies did not change, but their avidity to donor mismatches increased significantly after tapering (P = 0·035). In vitro addition of tacrolimus but not MPA strongly inhibited CTL alloreactivity during tapering and led to a significant shift to anti-inflammatory graft-specific cytokine production. Tapering of immunosuppression is characterized by diverse immune profiles that appear to relate inversely to plasma C-peptide levels. Highly avid allospecific CTLs that are known to associate with rejection increased during tapering, but could be countered by restoring immune suppression in vitro. Immune monitoring studies may help guiding tapering of immunosuppression after islet cell transplantation, even though we do not have formal prove yet that the observed changes reflect direct effects of immune suppression on immunity.
Responses of benthic macroinvertebrate communities to altitude and geology in tributaries of the Sepik River (Papua New Guinea): the influence of taxonomic resolution on the detection of environmental gradients
Authors: DUDGEON DAVID
Published: July 2012

1. Benthic macroinvertebrate communities were sampled in 30 tributary streams at altitudes from sea level to about 3000 m draining three geologically distinct regions within the catchment of the Sepik River, Papua New Guinea. The fauna of this near‐pristine river has been little studied, and the impacts of ongoing and anticipated human impacts on the Sepik are uncertain.

2. Data on community composition were analysed at different levels of taxonomic resolution (species or morphospecies versus family) to compare their responses to environmental variables such as altitude and geology (reflected in water chemistry), and to indicate their potential utility for the detection of environmental change.

3. A total of 183 000 macroinvertebrates representing 250 species were collected, predominantly insects (232 species and >99% of individuals). The fauna was co‐dominated by Diptera (42% of individuals; 32 morphospecies, mainly Orthocladiinae, Simuliidae and Chironominae) and Ephemeroptera (36%; 48 species), although the Trichoptera showed the highest species (67) and family (13) richness, with Coleoptera ranked third (43 species). Naucoridae (Heteroptera) and Crambidae: Acentropinae (Lepidoptera), each represented by 13 species, were distinctive faunal elements. Mayflies were represented by only four families, one consisting of a single species.

4. Multivariate analysis of the species‐level data set revealed that community composition was influenced by geological region, but the effect was largely due to altitude as most streams in one region (the Central Highlands) were at higher elevations (>800 m) than streams in the other two regions (<500 m). However, altitude had no direct effect on species richness. A secondary influence of current speed and a subsidiary effect of water chemistry (pH and N‐NO3) on community composition were also detected. Naucorid bugs showed evidence of altitudinal zonation and some species replacement, plus a tendency for certain genera to be associated with highland or lowland streams.

5. Analysis of the family‐level data set failed to uncover strong effects of any environmental variable, either individually or in combination, although some sensitivity to altitude plus slope was detected.

6. These findings suggest that attempts to use macroinvertebrates to detect environmental change in New Guinea streams will require species‐level monitoring of community composition.
The signal crayfish is not a single species: cryptic diversity and invasions in the Pacific Northwest range of Pacifastacus leniusculus
Authors: LARSON ERIC R. , ABBOTT CATHRYN L. , USIO NISIKAWA , AZUMA NORIKO , WOOD KIMBERLY A. , HERBORG LEIF‐MATTHIAS , OLDEN JULIAN D.
Published: July 2012

1. We used historical sources, morphology‐based taxonomy and mtDNA sequence data to address questions about the signal crayfish Pacifastacus leniusculus. These included evaluating unrecognised cryptic diversity and investigating the extent to which P. leniusculus may have been introduced within its presumed native range in the Pacific Northwest region of North America. Our study builds and expands on Pacific Northwest phylogeographic knowledge, particularly related to patterns of glacial refugia for freshwater species.

2. Extensive collections (824 specimens) from British Columbia (Canada), Idaho, Nevada, Oregon and Washington (United States) were used to characterise P. leniusculus at the mitochondrial 16S rRNA gene. Genetic groups within the species were elucidated by phylogenetics and amova; evolutionary relationships within the most common and diverse group were investigated using a statistical parsimony haplotype network, a nested amova, and tests of isolation by distance. Morphological measurements were used to relate findings of molecular analyses to three historically recognised P. leniusculus subspecies and characterise cryptic diversity by morphology.

3. We found substantial cryptic diversity, with three groups highly distinct from P. leniusculus in discrete geographic regions: the Chehalis River glacial refugium, Central Oregon and the Okanagan Plateau. Disjunct distributions of P. leniusculus relative to these cryptic groups and known patterns of Pleistocene glaciation and landscape evolution cast doubt on whether P. leniusculus is native to some areas such as coastal drainages of northern Washington and southern British Columbia. Morphological traits previously used to characterise P. leniusculus subspecies still persist but may be incapable of distinguishing P. leniusculus from newly discovered cryptic groups.

4. Cryptic diversity found within P. leniusculus highlights the pressing need for a thorough investigation of the genus Pacifastacus using data based on more extensive gene and taxon sampling. It also warrants conservation attention, as introductions of P. leniusculus within the Pacific Northwest may carry risks of hybridisation and introgression for cryptic groups. Owing to high genetic diversity and limited dispersal capacity relative to more vagile organisms like freshwater fish, crayfish of the genus Pacifastacus offer powerful potential insights into the geological history and phylogeography of the Pacific Northwest region. Finally, by shedding light on the long‐neglected native range of P. leniusculus, our results should also better inform our understanding of potential source populations for, and the ecology of, this important invasive species in regions including Europe, Japan and elsewhere in North America.
An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group
Authors: Lundin B. , Manco‐Johnson M. L. , Ignas D. M. , Moineddin R. , Blanchette V. S. , Dunn A. L. , Gibikote S. V. , Keshava S. N. , Ljung R. , Manco‐Johnson M. J. , Miller S. F. , Rivard G. E. , Doria A. S. ,   The International Prophylaxis Study Group
Published: July 2012

Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty‐one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty‐six of the joints were evaluated using two X‐ray scales. For all MRI scores, interreader agreement and correlations with X‐ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35–0.68) and with the X‐ray scores (Spearman correlation 0.40–0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X‐ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.
The unsayable: a concept analysis
Authors: Schick Makaroff Kara L.
Published: July 2012

Aim

To report an analysis of the concept of the unsayable.

Background

Within nursing, there is recognition that not all experiences of illness can be fully voiced and therefore may be unsayable. However, focus has been on that which is sayable, those experiences that can be communicated through language, leaving the unsayable unexamined. There is little examination of the meaning or relevance of the concept for nursing practice.

Data sources

The literature search was not limited by date and includes English, peer‐reviewed texts in the databasesCINAHL, Web of Science, and PsychINFOfrom 1959–2011.

Design

Rodgers' method of evolutionary concept analysis was used.

Review methods

References were read and analyzed according to surrogate terms, related concepts, attributes, antecedents, and consequences.

Results

Three surrogate terms, one related concept, four attributes, four antecedents, and two consequences were identified in this concept analysis. Based on this analysis, the unsayable refers to what is not expressed yet alluded to through language and may be conscious or unconscious. The meaning of this concept differs substantially between psychology and nursing.

Conclusion

Although literature on the unsayable has been developed primarily outside the discipline of nursing, exploration of the concept within nursing may assist nurses to consider situations and experiences that are challenging, elusive, and perhaps impossible for patients to language while living amid illness.
Research on nursing handoffs for medical and surgical settings: an integrative review
Authors: Staggers Nancy , Blaz Jacquelyn W.
Published: July 2012

Aims

To synthesize outcomes from research on handoffs to guide future computerization of the process on medical and surgical units.

Background

Handoffs can create important information gaps, omissions and errors in patient care. Authors call for the computerization of handoffs; however, a synthesis of the literature is not yet available that might guide computerization.

Data sources

PubMed, CINAHL, Cochrane, PsycINFO, Scopus and a handoff database from Cohen and Hilligoss.

Design

Integrative literature review.

Review methods

This integrative review included studies from 1980–March 2011 in peer‐reviewed journals. Exclusions were studies outside medical and surgical units, handoff education and nurses' perceptions.

Results

The search strategy yielded a total of 247 references; 81 were retrieved, read and rated for relevance and research quality. A set of 30 articles met relevance criteria.

Conclusion

Studies about handoff functions and rituals are saturated topics. Verbal handoffs serve important functions beyond information transfer and should be retained. Greater consideration is needed on analysing handoffs from a patient‐centred perspective. Handoff methods should be highly tailored to nurses and their contextual needs. The current preference for bedside handoffs is not supported by available evidence. The specific handoff structure for all units may be less important than having a structure for contextually based handoffs. Research on pertinent information content for contextually based handoffs is an urgent need. Without it, handoff computerization is not likely to be successful. Researchers need to use more sophisticated experimental research designs, control for individual and unit differences and improve sampling frames.
The role of epiphytism in architecture and evolutionary constraint within mycorrhizal networks of tropical orchids
Authors: MARTOS FLORENT , MUNOZ FRANÇOIS , PAILLER THIERRY , KOTTKE INGRID , GONNEAU CÉDRIC , SELOSSE MARC‐ANDRÉ
Published: July 2012

Characterizing the architecture of bipartite networks is increasingly used as a framework to study biotic interactions within their ecological context and to assess the extent to which evolutionary constraint shape them. Orchid mycorrhizal symbioses are particularly interesting as they are viewed as more beneficial for plants than for fungi, a situation expected to result in an asymmetry of biological constraint. This study addressed the architecture and phylogenetic constraint in these associations in tropical context. We identified a bipartite network including 73 orchid species and 95 taxonomic units of mycorrhizal fungi across the natural habitats of Reunion Island. Unlike some recent evidence for nestedness in mycorrhizal symbioses, we found a highly modular architecture that largely reflected an ecological barrier between epiphytic and terrestrial subnetworks. By testing for phylogenetic signal, the overall signal was stronger for both partners in the epiphytic subnetwork. Moreover, in the subnetwork of epiphytic angraecoid orchids, the signal in orchid phylogeny was stronger than the signal in fungal phylogeny. Epiphytic associations are therefore more conservative and may co‐evolve more than terrestrial ones. We suggest that such tighter phylogenetic specialization may have been driven by stressful life conditions in the epiphytic niches. In addition to paralleling recent insights into mycorrhizal networks, this study furthermore provides support for epiphytism as a major factor affecting ecological assemblage and evolutionary constraint in tropical mycorrhizal symbioses.
Detection of phytoecdysteroids by gustatory sensilla on chelicerae of the brown dog tick Rhipicephalus sanguineus
Authors: SOARES SARA F. , LOULY CARLA CRISTINA B. , NEVES CARLA A. , MARION‐POLL FRÉDÉRIC , BORGES LIGIA M. F.
Published: July 2012

Ecdysteroids are polyhydroxylated steroids that act as moulting hormones in arthropods and regulate several important life‐cycle processes. Phytoecdysteroids are ecdysteroid analogues produced by some plants that disrupt the growth and development of insects feeding on them, and can be perceived by the taste receptors of insects. The present study tested the hypothesis that the blood‐feeding tick Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) is capable of detecting phytoecdysteroids. By recording from the chelicerae, six phytoecdysteroids are tested: α‐ecdysone, 20‐hydroxyecdysone, ponasterone A, makisterone A, inokosterone and pterosterone. In unfed ticks, makisterone A and pterosterone elicit frequencies of neural impulses higher than in a negative control (a KCl solution at 10−3m), with detection thresholds of 10−6m and 10−12m, respectively. The spike amplitudes of the responses to these compounds, and also for 20‐hydroxyecdysone and ponasterone A, are higher than in the control, indicating that a different neurone may be involved: perhaps a deterrent cell, as observed in insects. In fed ticks, only pterosterone at 10−4m remains active. In behavioural attachment assays, no difference is observed between electrophysiologically active compounds and the negative control. These results show the capability of R. sanguineus ticks to detect phytoecdysteroids, although they do not clarify the role of ecdysteroids in tick biology, for which further studies are required.
From mouse to humans: discovery of theCACNG2pain susceptibility gene
Authors: Nissenbaum J
Published: July 2012

Chronic pain is a major healthcare problem affecting the daily lives of millions with enormous financial costs. The notorious variability and lack of efficient pain relief pharmaceuticals provide both genetic and therapeutic challenge. There are several genetic approaches that aim to uncover the molecular nature of pain phenotypes into their genetic components. Gene mapping using model organisms for various pain phenotypes has led to the identification of novel genes affecting susceptibility and response to pain stimuli. Translational studies have succeeded to tie those genes to human pain syndromes, thus suggesting new targets for drug discovery. In this short review, a perspective on pain genetics and the trajectory from pain phenotype to pain gene involving fine‐mapping strategies, bioinformatic analysis and microarray profiling alongside human association analysis will be introduced. This integrated approach has led to identification ofCACNG2as a novel neuropathic pain gene affecting pain susceptibility both in mice and humans. It also serves as a prototype for efficient and economic discovery of pain genes. Comparisons to other methods as well as future directions of pain genetics will be discussed as well.
Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation
Authors: Stuckless S , Green J , Dawson L , Barrett B , Woods MO , Dicks E , Parfrey PS
Published: July 2012

Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological cancer incidence and overall survival was compared in female mutation carriers who received gynecological screening (cases) and in matched controls. Controls were randomly selected from non‐screened mutation carriers who were alive and disease‐free at the age the case entered the screening program. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in controls (p = 0.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (p = 0.17). Two of three deaths in the screened group were the result of ovarian cancer. Mean survival in the screened group was 79 years compared to 69 years in the control group (p = 0.11), likely associated with concomitant colonoscopy screening. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo‐oophorectomy be considered in female mutation carriers who have completed childbearing.
The genetics of primary and secondary sexual character trade‐offs in a horned beetle
Authors: House C. M. , Simmons L. W.
Published: July 2012

When structures compete for shared resources, this may lead to acquisition and allocation trade‐offs so that the enlargement of one structure occurs at the expense of another. Among the studies of morphological trade‐offs, their importance has been demonstrated primarily through experimental manipulations and comparative analyses. Relatively, a few studies have investigated the underlying genetic basis of phenotypic patterns. Here, we use a half‐sibling breeding design to determine the genetic underpinnings of the phenotypic trade‐off between head horns and the male copulatory organ or aedeagus that has been found in the dung beetle Onthophagus taurus. Instead of the predicted negative genetic covariance among characters that trade‐off, we find positive genetic covariance between absolute horn and aedeagus length and zero genetic covariance between relative horn and aedeagus length. Therefore, although the genetic covariance between absolute horn and aedeagus length would constrain the independent evolution of primary and secondary sexual characters in this population, there was no evidence of a trade‐off. We discuss alternative hypotheses for the observed patterns of genetic correlation between traits that compete for resources and the implications that these have for selection and the evolution of such traits.
Ultrio and Ultrio Plus non‐discriminating reactives: false reactives or not?
Authors: Charlewood R. , Flanagan P.
Published: July 2012

Background  The low, fluctuating levels of DNA characteristic of occult hepatitis B infection make its detection by nucleic acid testing (NAT) a challenge.

Methods  Four year’s routine use of the Ultrio and Ultrio Plus assays in blood donations in New Zealand was analysed.

Results  0·09% of donations tested with Ultrio and Ultrio Plus assays showed reactivity in the multiplex assay, but non‐reactivity in all three discriminatory assays and relevant mandatory serological assays (anti‐HIV, anti‐HCV, HBsAg). These donations were more likely to be anti‐HBc reactive (Ultrio, 13%; Ultrio Plus, 57%; random donors, 6·8%). Thirty‐four per cent of these anti‐HBc‐reactive donations were also reactive in either an alternate NAT assay or on repeat multiplex testing. Thirteen per cent of the donors of the discriminatory‐negative, anti‐HBc‐reactive donations who had given other Ultrio‐ or Ultrio Plus‐tested donations had at least one other multiplex reactive donation.

Conclusion  These findings suggest that their HBV DNA levels are around the assay’s limit of detection, that false reactivity cannot be presumed when a donor fails to discriminate and that caution should be applied when deciding whether to continue accepting donations from such donors.
A study of blood transfusion services at a district hospital in Malawi
Authors: Bugge H. F. , Karlsen N. C. T. , Oydna E. , Rake M. M. , Wexels N. , Bendabenda J. , Roald B. , Heier H. E. , Chisuwo L. , Jourdan P. M.
Published: July 2012

Background and objectives  Severe anaemia is an important cause of mortality in developing countries. However, few studies have explored the use of and possibilities for blood transfusion services. The aims of this study are to explore the use of blood transfusion services at a hospital in sub‐Saharan Africa and to assess the quality of the transfusion services according to WHO guidelines.

Materials and methods  Patient age, gender, haemoglobin (Hb) level, diagnosis, hospital department and replacement donations were recorded for all blood transfusions administered at a district hospital in Malawi in January 2010. The laboratory equipment and procedures were scored according to WHO guidelines.

Results  The mean Hb of transfused patients was 4·8 g/dl. Fifty‐seven per cent (59/104) of the transfusions were given to children diagnosed with malaria, and 17% (18/104) were given to pregnant women. During the study period, blood was in stock and available for transfusion within 1 h of requisition. The equipment and procedures at this hospital met the main criteria for an adequate WHO stage of development.

Conclusion  In contrast to the advanced transfusion medicine in developed nations, our findings highlight the persistent and urgent need for life‐saving blood transfusions in especially young children and pregnant women in Africa. The results indicate that blood transfusion services adapted to local conditions may be a realistic solution for providing safe blood products in developing countries. Serious challenges, such as HIV transmission and sustainable organization of low‐risk blood donations should be addressed to assure access to safe blood products.
Labial adhesion causing voiding but not sexual problems in a married woman
Authors: Watanabe Takashi , Matsubara Shigeki , Ikeda Tomoe , Kawai Shina , Nakamura Shigeru , Nakai Hideo
Published: July 2012

A married woman of reproductive age had labial adhesion with voiding difficulty. She and her husband had not been bothered by their inability to engage in sexual intercourse for the 10 years of their marriage. Surgical incision and reconstruction disclosed the normal vaginal vestibule and urethral meatus. Six months after surgery, her labium was fully open without recurrence. We must be aware that labial adhesion may occur and be hidden in a woman of reproductive age, even when the patient does not notice any ‘abnormality’ in her genitalia.
Premature delivery due to intrauterine Candida infection that caused neonatal congenital cutaneous candidiasis: A case report
Authors: Ito Fumitake , Okubo Tomoharu , Yasuo Tadahiro , Mori Taisuke , Iwasa Koichi , Iwasaku Kazuhiro , Kitawaki Jo
Published: July 2012

Congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature. Neonates having this disease present with systemic skin lesions caused by intrauterine Candida infections. We present a case of threatened premature delivery due to Candida chorioamnionitis, which caused both maternal postpartum endometritis and neonatal congenital cutaneous candidiasis. A 34‐year‐old woman who was admitted for fetal membrane bulging at 20 weeks of gestation underwent McDonald cervical cerclage. We diagnosed threatened premature delivery due to intrauterine infection; therefore, we terminated the gestation by cesarean section at 24 weeks of gestation. Fungi‐like yeast was detected in infantile gastric juice. Histopathological findings of the placenta revealed that Candida albicans mycelium invaded the placenta, chorioamniotic membrane and umbilical cord.
TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like‐1 gene may have a role in stress urinary incontinence physiopathology
Authors: Ozbek Emin , Polat Emre Can , Ozcan Levent , Otunctemur Alper , Emrence Zeliha , Ustek Duran
Published: July 2012

Aim:  In experimental studies, lysyl oxidase like‐1 (LOX‐L1) (−/−) mice were shown to have similar pelvic floor dysfunction to female rats. LOX‐L1 levels in endopelvic fascia decrease as a result of increasing births in women with pelvic prolapse. For these reasons, we investigated the LOX‐L1 gene polymorphism, which has an important role in connective tissue and collagenous metabolism in stress urinary incontinence (SUI).

Materials and Methods:  A total of 87 women with SUI who underwent normal vaginal delivery and 87 controls were involved in the study. Single nucleotide gene polymorphisms in LOX‐L1's rs1048661, G > T, pArg141Leu, Exon‐1 SmaI; rs3825942, C > T, pGly153Asp, Hinf‐1 and rs2165241, C > T, İntron‐1 BsrI regions were searched. The results were statistically compared as alleles with 3 × 2 χ2‐test.

Results:  A total of 32 (34%) GG, 20 (21%) GT, 42 (45%) TT, 32 (37%) GG, 43 (39%) GT, 21 (24%) TT polymorphisms in rs1048661; 30 (36%) CC, 16 (19%) CT, 37 (45%) TT, 41 (59%) CC, 15 (22%) CT, 13 (19%) TT polymorphisms in rs2165241; and 63 (72%) CC, 21 (24%) CT, 3 (4%) TT; 48 (6%) CC, 22 (30%) CT, 3 (4%) TT polymorphisms in rs3825942 were found in patients and the control group, respectively. In patients, the TT polymorphism in the rs1048661 and rs2165241 region were found to be significant.

Conclusions:  The homozygote TT polymorphism in the rs1048661 and rs2165241 region of LOX‐L1 gene may be responsible from SUI physiopathology.
Some factors exerting an influence on the coaxing effect of austenitic stainless steels
Authors: AKITA M. , NAKAJIMA M. , UEMATSU Y. , TOKAJI K. , JUNG J.‐W.
Published: July 2012

The present paper describes some factors exerting an influence on the coaxing effect of austenitic stainless steels. Particularly, the influence of prestrain was investigated in detail. The materials used were austenitic stainless steels, type 304 and 316. Type 304N2 was also used to examine the properties of the stabilized austenitic phase in type 304. Two types of rotating bending fatigue tests, i.e. the conventional constant amplitude tests and stress‐incremental tests, were performed using the specimens subjected to the several tensile‐prestrain levels. Under the constant amplitude tests, the fatigue strengths of type 304 and 316 increased with increasing prestrain. Under the stress‐incremental tests, type 304 showed a remarkable coaxing effect, where the fatigue failure stress significantly increased regardless of the prestrain level. The coaxing effect in the unprestrained specimens was larger than those of the prestrained ones. Type 304N2 showed lower coaxing effect than type 304. In addition, the strain‐induced martensitic transformation did not occur because of the higher stability of austenitic phase in type 304N2. In type 316, the coaxing effect was dependent on the prestrain level, i.e. below 15% prestrain the coaxing effect became smaller with increasing prestrain, whereas above 25% prestrain the coaxing effect reappeared. Based on the tests results, it was considered that the coaxing effect in austenitic stainless steel was due to the mechanisms such as work hardening, strain ageing and strain‐induced martensitic transformation. The contribution of these mechanisms to the coaxing effect was different among type 304, 304N2 and 316.
Effect of saxagliptin on the pharmacokinetics of the active components of Ortho‐Cyclen®, a combined oral contraceptive containing ethinyl estradiol and norgestimate, in healthy women
Authors: Upreti V. V. , Hsiang C. B. , Li L. , Xu X. , LaCreta F. P. , Boulton D. W.
Published: July 2012

Saxagliptin (Onglyza™) is a dipeptidyl peptidase‐4 (DPP4) inhibitor for treating type 2 diabetes mellitus. This open‐label, randomized, two‐way crossover study in 20 healthy female subjects investigated the effect of saxagliptin on the pharmacokinetics (PK) of the active components of a combined oral contraceptive (COC). Subjects received either COC (Ortho‐Cyclen®) once daily (QD) for 21 days, then 5 mg saxagliptin QD + COC QD for 21 days, or vice versa. Coadministration of saxagliptin and COC did not alter the steady‐state PK of the primary active oestrogen (ethinyl estradiol) or progestin (norelgestromin) COC components. The area under the concentration–time curve (AUC) and peak plasma concentration (Cmax) of an active metabolite of norelgestromin (norgestrel) were increased by 13 and 17%, respectively, a magnitude that was not considered clinically meaningful. Coadministration of saxagliptin and COC in this study was generally well‐tolerated. Saxagliptin can be co‐prescribed with an oestrogen/progestin combination for women taking oral contraceptive.