bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of toxicity and factors influencing severity in acute adult trimipramine poisoning
Authors: Gutscher Karen , Rauber‐Lüthy Christine , Haller Marina , Braun Michèle , Kupferschmidt Hugo , Kullak‐Ublick Gerd A. , Ceschi Alessandro
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Trimipramine poisoning is a relatively frequent occurrence.

• Although differences between tricyclic antidepressants in receptor affinity and adverse effects profile are documented, previous overdose studies mostly summarize all tricyclics or they only compare the fatality rate of different antidepressants including trimipramine.

• The factors influencing the severity of trimipramine poisoning have not been previously investigated.

WHAT THIS STUDY ADDS

• We have demonstrated that trimipramine poisoning mainly occurs as a consequence of suicide attempts in young female patients and that moderate poisoning can already occur after ingestion of doses in the high therapeutic range.

• We were able to identify a clear dose–effect relationship, a minimal dose for moderate and severe toxicity and the dose bearing a 50% risk of developing moderate or severe symptoms.

• Our study suggests that patients with trimipramine poisoning might benefit from an early gastrointestinal decontamination.

AIMS To analyze the clinical features of trimipramine poisoning, identify a minimal toxic dose, and the dose bearing a 50% risk of developing a moderate, severe or fatal outcome.

METHODS All acute adult trimipramine monointoxications reported by physicians to the Swiss Toxicological Information Centre between January 1992 and December 2009 were identified.

RESULTS Two hundred and thirty cases (26 confirmed and 204 probable) were analyzed, the mean age was 35.7 years and 74% were females. One hundred and thirty‐seven patients showed mild, 54 moderate and 21 severe symptoms. Three cases were fatal due to refractory cardiovascular collapse. Ninety‐three per cent of the events were attempted or completed suicides. The most common symptoms were central nervous system depression (79.2%), tachycardia (19.1%) and QTc prolongation (13.9%). The severity of poisoning depended significantly on the ingested dose (P < 0.001). The minimal dose for moderate symptoms was 250 mg (median dose 1.2 g) and 850 mg for severe symptoms (median dose 2.7 g). The dose for a 50% risk of developing a moderate, severe or fatal outcome was 5.11 g. In 38 patients early gastrointestinal decontamination was performed. Overall, these patients ingested higher trimipramine doses than the late‐ or not‐decontaminated patients (P= 0.113). The median doses were also higher in the decontaminated group within each severity category except in the fatal cases.

CONCLUSIONS We demonstrated that moderate trimipramine poisoning can already occur after ingestion of doses in the high therapeutic range. Poisoned patients have to be monitored for central nervous system depression, dysrhythmias and QTc prolongation. Early decontamination might be beneficial.
Perifosine plus lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma: a Phase I Multiple Myeloma Research Consortium study
Authors: Jakubowiak Andrzej J. , Richardson Paul G. , Zimmerman Todd , Alsina Melissa , Kaufman Jonathan L. , Kandarpa Malathi , Kraftson Stephanie , Ross Charles W. , Harvey Colleen , Hideshima Teru , Sportelli Peter , Poradosu Enrique , Gardner Lesa , Giusti Kathy , Anderson Kenneth C.
Published: May 2012

The combination of lenalidomide–dexamethasone is active in multiple myeloma (MM). Preclinical data showed that the Akt inhibitor, perifosine, sensitized MM cells to lenalidomide and dexamethasone, providing the rationale for this Phase I, multicentre, single‐arm study to assess the safety and determine the maximum‐tolerated dose (MTD) of perifosine–lenalidomide–dexamethasone in relapsed and relapsed/refractory MM. Patients received escalating doses of perifosine 50–100 mg daily and lenalidomide 15–25 mg once daily on days 1–21 of each 28‐d cycle, plus dexamethasone 20–40 mg weekly thereafter, as indicated. Thirty‐two patients were enrolled across four dose cohorts. MTD was not reached, with 31 patients evaluable for safety/tolerability. The most common all‐causality grade 1‐2 adverse events were fatigue (48%) and diarrhoea (45%), and grade 3–4 neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). Among 30 evaluable patients, 73% (95% confidence interval, 57·5–89·2%) achieved a minimal response or better, including 50% with a partial response or better. Median progression‐free survival was 10·8 months and median overall survival 30·6 months. Response was associated with phospho‐Akt in pharmacodynamic studies. Perifosine–lenalidomide–dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory MM.
Nordic MCL2 trial update: six‐year follow‐up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC + autologous stem‐cell support: still very long survival but late relapses do occur
Authors: Geisler Christian H. , Kolstad Arne , Laurell Anna , Jerkeman Mats , Räty Riikka , Andersen Niels S. , Pedersen Lone B. , Eriksson Mikael , Nordström Marie , Kimby Eva , Bentzen Hans , Kuittinen Outi , Lauritzsen Grete F. , Nilsson‐Ehle Herman , Ralfkiær Elisabeth , Ehinger Mats , Sundström Christer , Delabie Jan , Karjalainen‐Lindsberg Marja‐Liisa , Brown Peter , Elonen Erkki
Published: May 2012

Mantle cell lymphoma (MCL) is a heterogenic non‐Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early – based on the median observation time of 4 years – results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event‐free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6·5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event‐free survival of 7·4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki‐67‐expression were the only independent prognostic factors. Subdivided by the MIPI‐Biological Index (MIPI + Ki‐67, MIPI‐B), more than 70% of patients with low‐intermediate MIPI‐B were alive at 10 years, but only 23% of the patients with high MIPI‐B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk‐adapted treatment strategy for MCL. The study was registered at www.isrctn.org as ISRCTN 87866680.
Current treatment protocols can offer a normal or near‐normal quality of life in the majority of patients with non‐functioning pituitary adenomas
Authors: Capatina Cristina , Christodoulides Constantinos , Fernandez Alberto , Cudlip Simon , Grossman Ashley B. , Wass John A. H. , Karavitaki Niki
Published: May 2012

Objective

Non‐functioning pituitary adenomas (NFA) may be associated with significant morbidity. Published data on the quality of life (QoL) of patients with NFA are scarce and conflicting. In view of the discordant findings and the advances in the management of these subjects, we aimed to evaluate the QoL in patients with NFA followed up in a tertiary endocrine UK referral centre.

Subjects and Methods

All consecutive patients with NFA attending the outpatient clinic in the Department of Endocrinology in Oxford over a 6‐month period (n = 193) were offered 3 health‐related QoL questionnaires [Short Form 36 (SF36), Nottingham Health Profile (NHP), European Quality of Life Scale (EuroQoL)] to complete. Patient outcomes (response rate 93·3%) were compared with age‐related UK reference values.

Results

None of the QoL scores in the SF‐36 or the 5 dimensions of health in the EuroQoL was different from the reference values. The visual analogue scale (VAS) score (EuroQoL) was slightly compromised (P = 0·041). In the NHP questionnaire, males had no parameter significantly affected, whereas females performed worse in 1/6 areas (energy levels). Tumour recurrence was an independent predictor for compromised VAS score and for anxiety/depression (EuroQoL), and visual field defects for more frequent problems with interests/hobbies (NHP).

Conclusions

Overall, the health‐related QoL and perception of subjective health in patients with NFA was not compromised to any major extent suggesting that we can now offer the prospect of treatment and replacement, which will provide a normal or near‐normal QoL. Specific groups are affected in various dimensions, necessitating measures to compensate for predisposing factors.
An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth
Authors: Drake Amanda J. , McPherson Rhoanne C. , Godfrey Keith M. , Cooper Cyrus , Lillycrop Karen A. , Hanson Mark A. , Meehan Richard R. , Seckl Jonathan R. , Reynolds Rebecca M.
Published: May 2012

Objective

In epidemiological studies, adverse early‐life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early‐life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth.

Design

We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring.

Measurements

DNA methylation at 11β‐hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin‐like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA.

Results

Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy.

Conclusions

Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early‐life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early‐life maternal diet and/or foetal growth and cardiovascular disease risk in humans.
Response of stream‐breeding salamander larvae to sediment deposition in southern Appalachian (U.S.A.) headwater streams
Authors: CONOR KEITZER S. , GOFORTH REUBEN R.
Published: May 2012

1. Increased fine sediment deposition is a prevalent threat to stream biodiversity and has been shown to impact stream‐breeding salamanders negatively. However, their complex life histories make it difficult to determine which stage is affected.

2. We conducted field experiments from 26 August to 11 September 2010 and 11 October to 11 November 2010 in two southern Appalachian headwater streams (U.S.A.) to examine the response of larval salamanders to increased fine sediment deposition. Fine sediment was increased in artificial stream channels by 0, 33 and 67%. The number of larvae observed at the end of the experiments was used to determine whether larval microhabitat selection was influenced by fine sediment deposition. A concurrent survey of aquatic larvae in three nearby streams complemented this experiment. Stream substratum composition at survey sites was quantified to examine the effects of fine sediment on larval salamander abundance.

3. Increases in fine sediment deposition failed to explain the number of larval salamanders detected in stream channels. Similarly, a negligible effect of fine sediment was observed on abundance estimates.

4. These results suggest that fine sediment deposition has a minimal impact on aquatic salamander larvae. Therefore, the effects of increased fine sediment loads on stream‐breeding salamanders may not be the result of deleterious effects on the aquatic larvae but instead may be the result of effects on other stages. Management efforts that consider these other stages are therefore needed to protect stream‐breeding salamander communities.
Herbivore‐induced aspen volatiles temporally regulate two different indirect defences in neighbouring plants
Authors: Li Tao , Holopainen Jarmo K. , Kokko Harri , Tervahauta Arja I. , Blande James D.
Published: May 2012

1. Many plant species have two inducible indirect defences against herbivores, emission of volatile organic compounds (VOCs) and secretion of extrafloral nectar (EFN). Moreover, herbivore‐induced VOCs can serve as airborne signals in plant–plant communication, inducing and/or priming defences in undamaged neighbouring plants. However, it remains largely unknown, particularly in woody plants, whether herbivore‐induced VOCs induce and/or prime these two indirect defences simultaneously.

2. We investigated the VOC‐mediated induction and priming of VOC emission and EFN secretion in the woody plant hybrid aspen (Populus tremula × Populus tremuloides) in the context of plant–plant communication. Hybrid aspen saplings were exposed to VOCs released either from herbivore‐infested or uninfested conspecifics and subsequently challenged by herbivores. VOCs and EFN from exposed plants were collected throughout experiments. Additionally, local and systemic EFN induction was investigated.

3. Exposure to VOCs from infested plants directly induced secretion of EFN sugars but not emission of volatile terpenes. Upon subsequent herbivore attack, however, plants previously exposed to herbivore‐induced VOCs released significantly more terpenes than unexposed plants, whereas EFN secretion was not increased, indicating that herbivore‐induced VOCs prime VOC emission but not EFN secretion. This switching in the indirect defence priority from induced EFN secretion to primed VOC emission may reflect the potential fitness disadvantages of VOC emission and EFN secretion on their own. In addition, feeding by Epirrita autumnata larvae reduced EFN sugar production both locally and systemically, which disagrees with previous findings and suggests that EFN secretion varies depending on plant and herbivore species.

4. Thereby, our work has parallels and divergences from the most significant previous studies. Nevertheless, it suggests that plants can respond differently to early warning signals and ensuing herbivory and in doing so fine‐tune their different indirect defences timely to achieve optimal use of resources.
How do temperate bryophytes face the challenge of a changing environment? Lessons from the past and predictions for the future
Authors: Désamoré Aurélie , Laenen Benjamin , Stech Michael , Papp Beata , Hedenäs Lars , Mateo Ruben G. , Vanderpoorten Alain
Published: May 2012

Bryophytes are a group of early land plants, whose specific ecophysiological and biological features, including poikilohydry, sensitivity to moderately high temperature and high dispersal ability, make them ideal candidates for investigating the impact of climate changes. Employing a combined approach of species distribution modelling (SDM) and molecular phylogeography in the temperate moss Homalothecium sericeum, we explore the significance of the Mediterranean refugia, contrasting the southern and northern refugia hypotheses, determine the extent to which recolonization of previously glaciated areas has been facilitated by the high dispersal ability of the species and make predictions on the extent to which it will be impacted by ongoing climate change. The Mediterranean areas exhibit the highest nucleotidic diversities and host a mixture of ancestral, endemic and more recently derived haplotypes. Extra‐Mediterranean areas exhibit low genetic diversities and Euro‐Siberian populations display a significant signal of expansion that is identified to be of Euro‐Siberian origin, pointing to the northern refugia hypothesis. The SDMs predict a global net increase in range size owing to ongoing climate change, but substantial range reductions in southern areas. Presence of a significant phylogeographical signal at different spatial scales suggests, however, that dispersal limitations might constitute, as opposed to the traditional view of spore‐producing plants as efficient dispersers, a constraint for migration. This casts doubts about the ability of the species to face the massive extinctions predicted in the southern areas, threatening their status of reservoir of genetic diversity.
Incident radiation and the allocation of nitrogen within Arctic plant canopies: implications for predicting gross primary productivity
Authors: Street Lorna E. , Shaver Gaius R. , Rastetter Edward B. , van Wijk Mark T. , Kaye Brooke A. , Williams Mathew
Published: May 2012

Arctic vegetation is characterized by high spatial variability in plant functional type (PFT) composition and gross primary productivity (P). Despite this variability, the two main drivers of P in sub‐Arctic tundra are leaf area index (LT) and total foliar nitrogen (NT). LT and NT have been shown to be tightly coupled across PFTs in sub‐Arctic tundra vegetation, which simplifies up‐scaling by allowing quantification of the main drivers of P from remotely sensed LT. Our objective was to test the LT–NT relationship across multiple Arctic latitudes and to assess LT as a predictor of P for the pan‐Arctic. Including PFT‐specific parameters in models of LT–NT coupling provided only incremental improvements in model fit, but significant improvements were gained from including site‐specific parameters. The degree of curvature in the LT–NT relationship, controlled by a fitted canopy nitrogen extinction co‐efficient, was negatively related to average levels of diffuse radiation at a site. This is consistent with theoretical predictions of more uniform vertical canopy N distributions under diffuse light conditions. Higher latitude sites had higher average leaf N content by mass (NM), and we show for the first time that LT–NT coupling is achieved across latitudes via canopy‐scale trade‐offs between NM and leaf mass per unit leaf area (LM). Site‐specific parameters provided small but significant improvements in models of P based on LT and moss cover. Our results suggest that differences in LT–NT coupling between sites could be used to improve pan‐Arctic models of P and we provide unique evidence that prevailing radiation conditions can significantly affect N allocation over regional scales.
Marine invertebrate skeleton size varies with latitude, temperature and carbonate saturation: implications for global change and ocean acidification
Authors: Watson Sue‐Ann , Peck Lloyd S. , Tyler Paul A. , Southgate Paul C. , Tan Koh Siang , Day Robert W. , Morley Simon A.
Published: May 2012

There is great concern over the future effects of ocean acidification on marine organisms, especially for skeletal calcification, yet little is known of natural variation in skeleton size and composition across the globe, and this is a prerequisite for identifying factors currently controlling skeleton mass and thickness. Here, taxonomically controlled latitudinal variations in shell morphology and composition were investigated in bivalve and gastropod molluscs, brachiopods, and echinoids. Total inorganic content, a proxy for skeletal CaCO3, decreased with latitude, decreasing seawater temperature, and decreasing seawater carbonate saturation state (for CaCO3 as calcite (Ωcal)) in all taxa. Shell mass decreased with latitude in molluscs and shell inorganic content decreased with latitude in buccinid gastropods. Shell thickness decreased with latitude in buccinid gastropods (excepting the Australian temperate buccinid) and echinoids, but not brachiopods and laternulid clams. In the latter, the polar species had the thickest shell. There was no latitudinal trend in shell thickness within brachiopods. The variation in trends in shell thickness by taxon suggests that in some circumstances ecological factors may override latitudinal trends. Latitudinal gradients may produce effects similar to those of future CO2‐driven ocean acidification on CaCO3 saturation state. Responses to latitudinal trends in temperature and saturation state may therefore be useful in informing predictions of organism responses to ocean acidification over long‐term adaptive timescales.
Tertiary prophylaxis in adults: is there a rationale?
Authors: Gringeri A. , Lambert T. , Street A. , Aledort L.
Published: May 2012

There is lack of evidence‐based recommendations or clear‐cut consensus regarding the clinical and economic utility of regular prophylaxis started in adulthood, with the aim of keeping the clinical situation from getting worse by prevention of further bleeds contributing to increasing musculo‐skeletal or other morbidity in haemophilia. Such a prophylaxis program has been shown in relatively small cohorts to be effective in reducing bleeding occurrence, with a variable effect on the joint status, but with significantly higher factor consumption and consequently higher costs than on‐demand therapy. There has been no attempt to identify subsets of patients who may benefit from “tertiary” prophylaxis more than others, for example, due to their bleeding phenotype and/or requirements for product issued on‐demand or to identify the dosage that provides the optimal balance of clinical benefit and cost effectiveness. This article reviews the published literature on prophylaxis started beyond the age of 18 years, the barriers to the uptake of prophylaxis programs particularly in adults and highlights areas in need of further research.
Haemophilia Care in Europe: the ESCHQoL study
Authors: Schramm W. , Gringeri A. , Ljung R. , Berger K. , Crispin A. , Bullinger M. , Giangrande P. L. F. , Von Mackensen S. , Mantovani L. G. , Nemes L. , Serban M. ,   For the eschqol study group
Published: May 2012

The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross‐sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (<1%). More than half of the adults were carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8% children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount of clotting factor used in patients' region of residence in 2005: region 1: >5 IU; region 2: 2–5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence.
Analysis of F9 point mutations and their correlation to severity of haemophilia B disease
Authors: Hamasaki‐Katagiri N. , Salari R. , Simhadri V. L. , Tseng S. C. , Needlman E. , Edwards N. C. , Sauna Z. E. , Grigoryan V. , Komar A. A. , Przytycka T. M. , Kimchi‐Sarfaty C.
Published: May 2012

Haemophilia B is an X‐linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non‐severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed‐rank tests showed highly significant differences between severe and non‐severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins.
Acute pain management and assessment: are guidelines being implemented in developing countries (Lebanon)
Authors: Zeitoun Abeer A. , Dimassi Hani I. , Chami Bahija A. , Chamoun Nibal R.
Published: May 2012

Rationale  Pain assessment and treatment is influenced by subjective perception of pain. Despite the international efforts to implement guidelines and protocols for pain management, pain continues to be regarded as a complication rather than a primary problem. The literature pertaining to the adequacy of pain management in the Middle East is frail. This study focuses on revealing the implemented practices of initial pain assessment, follow‐up and re‐evaluation of pain treatment in Lebanese hospitals.

Aim and objectives  The objective of this study is to evaluate the presence and effectiveness of acute pain management and its impact on the quality of life in hospitals throughout Lebanon, in both cancer and non‐cancer populations.

Methods  A Lebanese multi‐centre, prospective, chart review study was conducted over a period of 3 months. Data on demographics, pain medication, dose, route, duration and adjunct pain management were collected. Appropriateness of pain management was determined as per World Health Organization guidelines. Institutional Review Board approvals were obtained from each hospital.

Results  Results from 582 participants revealed that 50% of initial pain assessment intensity scores were based on the assumptions of health care professionals. Furthermore, as pain severity scores increased, the adequacy of pain management decreased. Only 22% of the patients had a daily follow‐up, and the majority of those continued to receive inappropriate therapy.

Conclusion  This study reflects the lack of a well‐structured system for pain management in Lebanese hospitals. It underlines the need for pain research in the region. It also highlights the need for implementing the recommendations discussed to minimize risk and optimize pain management.
Problem perception, technology and effectiveness in medical practice
Authors: Holmberg Leif
Published: May 2012

Rationale, aims and objectives  Evidence‐based medicine and clinical guidelines have been found difficult to implement in the clinical practice – mainly because lack of evidence quality and guidelines that, generally, do not account for variations in the medical cases. Variation in the medical cases enhances task uncertainty and uncertainty seems to be further enhanced through clinical guidelines. In this article, concept development is attempted, where task uncertainty is classified into a few medical problem‐solving processes according to differences in medical technology and in the (initial) perception of the medical problem. Furthermore is argued the need for using different strategies in evaluating performance quality in medical health care depending on the variation in the degree of task uncertainty.

Method  Qualitative data about medical activities related to certain diseases are used to exemplify problem‐solving processes representing different types of task uncertainty.

Results  It is argued that the main characteristics of medical problem‐solving processes vary according to differences in medical technology and perception of perceived medical problem. Four main medical problem‐solving processes are defined and demonstrated through empirical examples.

Conclusion  What may be regarded as rational behaviour is different for each type of problem‐solving processes. Consequently, the processes need different organizational settings and need to be evaluated according to different criteria. Furthermore, from a practical point of view, development and education related to problem perception would seem as important as development of medical technology.
Exploring sources of knowledge utilized in practice among Jordanian registered nurses
Authors: Al‐Ghabeesh Suhair Husni , Abu‐Moghli Fathieh , Salsali Mahvash , Saleh Mohammad
Published: May 2012

Rationale, aims and objectives  Understanding sources of knowledge used in everyday practice is very helpful in improving the quality of health care services. There is a consensus in the literature that nurses mostly relied in their practice on experiential knowledge gained through their interactions with other members of health care professionals and patients. The general aim of this study is to explore the sources of knowledge Jordanian registered nurses use during their practice.

Method  A descriptive correlational design was used to collect data from 539 Jordanian registered nurses from 10 hospitals using a self‐administered questionnaire.

Results  The mean year of experience of the sample was 7.08 years. Of the 615 questionnaires distributed, 555 were returned. This yields a response rate of 87.6%. Results revealed that the top five ranked sources used by Jordanian registered nurses include: the information that nurses learned during nursing education, personal experience in nursing over time, what was learned through providing care to patients, information gained through discussion between physicians and nurses about patients, and information from policy and procedure manuals.

Conclusion  Jordanian registered nurses recognize the value of research and that research utilization (RU) is an important issue and must not be ignored. The study has many implications for practice, education and research. Health care managers and decision makers need to play a more visible and instrumental role in encouraging RU to improve patients' quality of life.
Bio‐psycho‐social assessment of occlusal dysaesthesia patients
Authors: TSUKIYAMA Y. , YAMADA A. , KUWATSURU R. , KOYANO K.
Published: May 2012

Summary  Dentists occasionally experience occlusal dysaesthesia (OD) patients, who complain of bite discomfort without evident occlusal abnormalities. It is suggested that this condition is related to somatosensory abnormalities of the trigeminal system and/or psychological problems such as somatoform disorders. The aim of this study was to investigate the characteristics of OD with a bio‐psycho‐social approach. Twelve OD patients (10 women, two men; mean age 54·7 years) and twelve healthy volunteers (10 women, two men; mean age 54·8 years) were selected. They were assessed using (i) interdental thickness discrimination ability test using 2‐, 5‐ and 10‐mm‐thick standard blocks and 12 test blocks that were thinner or thicker than the corresponding standard block and (ii) psychological tests: General Health Questionnaire (GHQ60) and Profile of Mood States (POMS) brief‐form. There was no significant difference in the interdental thickness discrimination ability between OD patients and controls (mixed‐model anova, P = 1·000). Regarding psychological tests, there were no significant differences between OD patients and controls in the total scores for either GHQ60 (P = 0·143) or POMS brief‐form (P = 0·319) (Wilcoxon’s test). However, OD patients showed significant differences from controls in several subscales, that is, ‘somatic symptoms’ (P = 0·039) and ‘severe depression’ (P = 0·039) for GHQ60 and ‘depression‐dejection’ (P = 0·014) and ‘vigour’ (P = 0·008) for POMS brief‐form (Wilcoxon’s test). These results suggest there is no difference in interdental thickness discrimination ability between OD patients and normal controls, but OD patients tend to score higher on psychosomatic distress.
Anti‐interferon‐α neutralizing antibody is associated with nonresponse to pegylated interferon‐α plus ribavirin in chronic hepatitis C
Authors: Matsuda F. , Torii Y. , Enomoto H. , Kuga C. , Aizawa N. , Iwata Y. , Saito M. , Imanishi H. , Shimomura S. , Nakamura H. , Tanaka H. , Iijima H. , Tsutsui H. , Tanaka Y. , Nishiguchi S.
Published: May 2012

Summary.  Pegylated interferon‐α (PEG‐IFN‐α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20–50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti‐IFN‐α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN‐α as a standard. We studied 129 PEG‐IFN‐α/RBV‐treated patients. In the 82 end‐of‐treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG‐IFN‐α treatment, and detected 12 with NAbs. Patients with good IFN‐responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin‐28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN‐β (nIFN‐β) and re‐treatement of patients with NAbs with nIFN‐β/RBV achieved SVR. Our analyses revealed that the emergence of anti‐IFN‐α NAbs was a candidate causal factor of PEG‐IFN‐α‐treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG‐IFN‐α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti‐IFN‐α NAbs, should be considered.
Lymphedematous verrucous changes simulating squamous cell carcinoma in long‐standing hidradenitis suppurativa
Authors: Chu Emily Y. , Kovarik Carrie L. , Lee Robert A.
Published: May 2012

Background  Hidradenitis suppurativa (HS) is a relatively common condition marked by abscesses, sinus tracts, and scarring in intertriginous regions of the body. Lymphedema is an under‐recognized consequence of chronic inflammation in the setting HS.

Methods  We report five cases of patients with lymphedema resulting from long‐standing HS; the patients were seen either in a specialty HS clinic or general dermatology clinic at our institution. Biopsies for histologic analysis were performed on four of the five patients reported here.

Results  Changes of lymphedema may be manifested diffusely as widespread plaques or focally as verrucous papules and nodules. The latter may be difficult to distinguish clinically from squamous cell carcinoma, another complication of chronic HS. Histopathologic features of lymphedema include dilated lymphatic channels, diffuse edema, verrucous epidermal hyperplasia, mixed inflammation, and dermal fibrosis.

Conclusion  Lymphedema associated with chronic HS, which we also term “verrucous lymphostasis,” encompasses a spectrum of clinical and histopathologic findings. Squamous cell carcinoma may mimic focal presentations of lymphedema, and biopsy may be necessary to distinguish the two.
Evaluating suitable internal control genes for transcriptional studies in heat‐stressed mammary explants of buffaloes
Authors: Sodhi M. , Kishore A. , Khate K. , Kapila N. , Mishra B.P. , Kataria R.S. , Mohanty A.K. , Varshney N. , Mukesh M.
Published: May 2012

It is now a well‐accepted notion that each new experimental design requires proper evaluation of internal control genes (ICGs) for accurate normalization of expression data. In riverine buffaloes, till date no appropriate ICG has been reported for studying transcriptional response under any of the physiological stressful condition. The objective here was to test 16 well‐known reference genes from different functional categories that could serve as suitable ICG during heat stress studies in buffalo mammary tissue. Briefly, the mammary explants were exposed to 45°C for 1 h and subsequently allowed to recover at 37°C for different time points (2–24 h). Three software programs, geNorm, Normfinder and BestKeeper, were used to measure gene transcript stability. RPL22 was excluded because of weak amplification and unacceptable PCR efficiency. Except GAPDH, all other genes showed expression stability within the acceptable range (<1.5). RPL4, B2M, RPS23 and EEF1A1 genes were found to be most stably expressed while GAPDH and ACTB showed least stability. The BestKeeper analysis identified high correlation for RPL4 (r = 0.953) and EEF1A1 (r = 0.914) with BestKeeper index. Based on the present findings, it could be suggested that geometric average of RPL4, B2M, RPS23 and EEF1A1 would provide accurate normalization to transcriptional data of buffalo mammary explant in response to heat stress.
Characteristics of F1 Hybrids and Inbred lines in Octoploid Strawberry (Fragaria × ananassa Duchesne)
Authors: Rho Il Rae , Woo Jong Gyu , Jeong Ho Jeong , Jeon Heung Yong , Lee Choon‐Hwan
Published: May 2012

With 4 figures and 3 tables

The strawberry (Fragaria × ananassa Duchesne) plant is an octoploid vegetative propagated plant, and its cultivation is labour intensive in comparison with other plants propagated from seeds. The aims of this study were to develop an inbred line from octoploid strawberry and to generate an F1 hybrid cultivar through the combination of inbred lines. All inbred lines were obtained through selfing using five cultivars. Inbred lines were produced by selecting the best individuals for further inbreeding from each of the previous generations. Plant vigour and yield in inbred lines were low compared with the original cultivar, but completely recovered in the F1 hybrid. Breeding of inbred lines in octoploid strawberry can be achieved if individuals showing inbreeding depression are eliminated and vigorous individuals are selected, resulting in a strong heterosis of F1 hybrids through crossing between inbred lines.
Molecular mapping of the vein colour locus in Solanum venturii
Authors: Park Tae‐Ho
Published: May 2012

With 2 figures

The genetic background of red or purple pigments derived from anthocyanin has not been firmly identified in potato, although the trait of tuber colour has been considered a breeding target owing to its visual appeal and valuable antioxidants in the human diet. In this study, we evaluated the genetic segregation of vein colour in the mapping population derived from a cross within a wild potato species, Solanum venturii. The segregation ratio was 1 : 1 for purple and green colours, indicating the gene for vein colour was monogenically inherited. The genetic position of the vein colour locus was expected to be on potato chromosome 4 with the bridged molecular markers, PATMATC_499 and RGH3. These results will facilitate the characterization and cloning of pigmentation‐related genes, and the colours of above‐ground tissues could be used as selection markers for accelerating the breeding of colour potatoes.
Efficient targeted mutagenesis of the chordate Ciona intestinalis genome with zinc‐finger nucleases
Authors: Kawai Narudo , Ochiai Hiroshi , Sakuma Tetsushi , Yamada Lixy , Sawada Hitoshi , Yamamoto Takashi , Sasakura Yasunori
Published: May 2012

Zinc‐finger nucleases (ZFNs) are engineered nucleases that induce DNA double‐strand breaks (DSBs) at target sequences. They have been used as tools for generating targeted mutations in the genomes of multiple organisms in both animals and plants. The DSB induced by ZFNs is repaired by non‐homologous end joining (NHEJ) or by homologous recombination (HR) mechanisms. Non‐homologous end joining induces some errors because it is independent of a reference DNA sequence. Through the NHEJ mechanism, ZFNs generate insertional or deletional mutations at the target sequence. We examined the usability, specificity and toxicity of ZFNs in the basal chordate
Ciona intestinalis. As the target of ZFNs, we chose an
enhanced green fluorescent protein (EGFP)
gene artificially inserted in the
C. intestinalis genome because this locus is neutral for the development and growth of
C. intestinalis, and the efficiency of mutagenesis with ZFNs can thus be determined without any bias. We introduced
EGFP
‐ZFN mRNAs into the embryos of an
EGFP
‐transgenic line and observed the mutation frequency in the target site of
EGFP
. We also examined the effects of the
EGFP
‐ZFNs at off‐target sites resembling the
EGFP
target sequence in the
C. intestinalis genome in order to examine the specificity of ZFNs. We further investigated the influence of ZFNs on embryogenesis, and showed that adequate amounts of ZFNs, which do not disrupt embryogenesis, can efficiently induce mutations on the on‐target site with less effect on the off‐target sites. This suggests that target mutagenesis with ZFNs will be a powerful technique in
C. intestinalis.
Anatomy and ultrastructure of the floral nectary in Peganum harmala L. (Nitrariaceae)
Authors: ABEDINI MASUMEH , MOVAFEGHI ALI , ALIASGHARPOUR MAHBUBEH , DADPOUR MOHAMMAD REZA
Published: May 2012

Anatomy and ultrastructure of the floral nectary of Peganum harmala L. were studied using light and transmission electron microscopy. The floral nectary was visible as a glabrous, regularly five‐lobed circular disc encircling the base of the ovary. Anatomically, it comprised a single layered epidermis and 15–20 layers of small, subepidermal secretory cells overlying several layers of large, ground parenchyma cells. The floral nectary was supplied by phloem and both sieve tubes and companion cells were found adjacent to the ground parenchyma. Based on our ultrastructural observations, plastids of secretory cells during the early stages of development were rich in starch grains and/or osmiophilic plastoglobuli, but these disappeared as nectar secretion progressed. The nectar appeared to exude through the modified stomata along symplastic and apoplastic routes. The abundant plastids and mitochondria suggest an eccrine mechanism of nectar secretion in P. harmala.
Pulmonary hemorrhage in very low‐birthweight infants: Risk factors and management
Authors: Chen Ying‐Yao , Wang Hsiao‐Ping , Lin Shu‐Ming , Chang Jenn‐Tzong , Hsieh Kai‐Sheng , Huang Fu‐Kuei , Chiou Yee‐Hsuan , Huang Yung‐Feng ,   Taiwan Premature Infant Development Collaborative Study Group
Published: May 2012

Background:  Beginning 2007, the intratracheal route of epinephrine to end massive pulmonary hemorrhage (MPH) in very low‐birthweight (VLBW) infants was modified at Kaohsiung Veterans General Hospital. The aim of the present study was to assess the change in outcomes for these infants, and to evaluate the risk factors of MPH.

Methods:  Using the database of the Premature Baby Foundation of Taiwan, the mortality, risk factors and characteristics of VLBW infants with or without MPH were compared between 2000–2006 and 2007–2010.

Results:  Between January 2000 and December 2010, 399 VLBW infants were admitted to Kaohsiung Veterans General Hospital. Mean birthweight (BW) was 1099.6 ± 272.7 g, and mean gestational age (GA) was 28.7 ± 2.9 weeks. The overall survival rate was 84.2%. Sixteen (4%) had MPH: 11 in the first group (2000–2006; 18.2% survival rate), and five in the second group (2007–2010; 80% survival rate; P= 0.0000002). Infants with MPH had lower mean BW (864.9 ± 301.4 g, P= 0.0004), smaller mean GA (26.1 ± 2.0 weeks, P= 0.0002), significantly lower Apgar scores at 1 and 5 min, higher severity of respiratory distress syndrome (RDS; grades 3 or 4), and greater use of surfactant than infants without MPH. They also had more intraventricular hemorrhage and higher mortality.

Conclusions:  Smaller GA, lower BW, lower Apgar scores at 1 and 5 min, severe RDS (grades 3 or 4), and use of surfactant place VLBW infants at greater risk of MPH. Proper prenatal care and preventing premature labor and delivery were the most important preventative factors. A quick, deep thrust of intratracheal epinephrine with a catheter may improve survival.
Grief reaction model of families who experienced acute bereavement in Japan
Authors: Tatsuno Junko , Yamase Hiroaki , Yamase Yoshie
Published: May 2012

The present study clarified the structure of factors that affect grief reactions of families who experienced acute bereavement in critical care settings in Japan. Sixty‐four families who experienced acute bereavement answered a questionnaire. The questionnaire included the Miyabayashi Grief Measurement, recognition of bereavement, Multidimensional Scale of Perceived Social Support, and the Tri‐Axial Coping Scale. We analyzed the causal structure regarding the relationship of stress recognition, coping, and grief reactions using structural equation modeling. The greatest influence on grief reactions of bereaved families was stress recognition. Factors that influenced stress recognition were subjective degree of sadness, acceptance of bereavement, regret for bereavement, and recognition of a peaceful death. These results show that the quality of end‐of‐life care in critical care settings is an important factor that affects bereaved families' stress recognition and grief reactions. Nurses and medical staff must provide end‐of‐life care to help family members accept the death of their loved one and reduce regrets as much as possible.
Development of a patient‐specific simulator for laparoscopic renal surgery
Authors: Makiyama Kazuhide , Nagasaka Manabu , Inuiya Toru , Takanami Kentaro , Ogata Masato , Kubota Yoshinobu
Published: May 2012

Objectives:  To describe the development of a patient‐specific simulator for laparoscopic renal surgery.

Methods:  Image data of each patient scheduled to undergo laparoscopic renal surgery are captured by the simulator, enabling each patient's organs to be reproduced. The surgeon can carry out a preoperative “rehearsal” of the operation by using a simulator based on patient‐specific data.

Results:  The simulator is programmed to be adapted to both laparoscopic and retroperitoneoscopic surgery. The scope and the trocars can be located anywhere on the skin, and visualized on the monitor of the simulator. Dissection of the renal hilum can be simulated based in the anatomy of each patient. The haptic device of the simulator provides interactive resistance between the organs and surgical tools during the simulation.

Conclusions:  This patient‐specific simulator has been developed with the purpose of providing surgeons with a practical training tool for laparoscopic renal surgery. Using specific data for each patient, the simulator enables surgeons to carry out a “rehearsal” operation.