Search

It is easy to dismiss staying with a bad plan as foolish, but most people are at risk of falling into this trap under the right circumstances. Plan continuation bias and escalation of commitment are two traps that have doomed many a project and plan. Thoughtfully applying design thinking can help overcome these obstacles and lead to successful outcomes. [ABSTRACT FROM AUTHOR]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2019 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2019 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2019 article‐registration‐date‐month 3 article‐registration‐date‐day 9 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2019_Article_226.pdf target‐type OnlinePDF issue‐type Regular article‐type ReviewPaper journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection Medicine --> Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with limited response to cytotoxic chemoradiotherapy, as well as newer immunotherapies. The PDA tumor microenvironment contains infiltrating immune cells including cytotoxic T cells; however, there is an overall immunosuppressive milieu. Hypoxia is a known element of the solid tumor microenvironment and may promote tumor survival. Through various mechanisms including, but not limited to, those mediated by HIF‐1α, hypoxia also leads to increased tumor proliferation and metabolic changes. Furthermore, epithelial to mesenchymal transition is promoted through several pathways, including NOTCH and c‐MET, regulated by hypoxia. Hypoxia‐promoted changes also contribute to the immunosuppressive phenotype seen in many different cell types within the microenvironment and thereby may inhibit an effective immune system response to PDA. Pancreatic stellate cells (PSCs) and myofibroblasts appear to contribute to the recruitment of myeloid derived suppressor cells (MDSCs) and B cells in PDA via cytokines increased due to hypoxia. PSCs also increase collagen secretion in response to HIF‐1α, which promotes a fibrotic stroma that alters T cell homing and migration. In hypoxic environments, B cells contribute to cytotoxic T cell exhaustion and produce chemokines to attract more immunosuppressive regulatory T cells. MDSCs inhibit T cell metabolism by hoarding key amino acids, modulate T cell homing by cleaving L‐selectin, and prevent T cell activation by increasing PD‐L1 expression. Immunosuppressive M2 phenotype macrophages promote T cell anergy via increased nitric oxide (NO) and decreased arginine in hypoxia. Increased numbers of regulatory T cells are seen in hypoxia which prevent effector T cell activation through cytokine production and increased CTLA‐4. Effective immunotherapy for pancreatic adenocarcinoma and other solid tumors will need to help counteract the immunosuppressive nature of hypoxia‐induced changes in the tumor microenvironment. Promising studies will look at combination therapies involving checkpoint inhibitors, chemokine inhibitors, and possible targeting of hypoxia. While no model is perfect, assuring that models incorporate the effects of hypoxia on cancer cells, stromal cells, and effector immune cells will be crucial in developing successful therapies. [ABSTRACT FROM AUTHOR]

Graphene-based nanomaterials (GBN) have many potential biomedical applications. However, information regarding their biological properties and interactions with cells and/or soluble factors within a complex tissue is limited. The objective of this study was to use the growing feather (GF) of chickens as a minimally invasive cutaneous test-site to assess and monitor leukocyte recruitment in response to intradermal GBN injection. Specifically, the dermis of 20 GFs per chicken was injected with 10 μl of phosphate-buffered saline (PBS)-vehicle or 10 μl of 300 μg ml−1 oxygen-functionalized (f) GBN (6 chickens/treatment). GFs were collected before- (0) and at 0.25, 1, 2, 3, 4, 5, and 7 days post-injection and used for leukocyte-population analysis of immunofluorescently stained pulp cell suspensions or histological examination. Based on flow-cytometric cell population analysis, lymphocytes and macrophages were the major leukocyte-populations infiltrating GFs in response to f-GBN presence. Compared with PBS-controls, levels of T cells (γδ-, αβ-, CD4- and CD8-T cells) were greatly elevated in f-GBN-injected GFs within 6 h and remained elevated throughout the 7-day examination period. f-GBN's effects on local tissue leukocyte recruitment were not reflected in the blood, except for a higher percentage of lymphocytes on 7 days. These observations together with a visual examination of f-GBN-injected GF tissue-sections suggest a delayed-type hypersensitivity-like, inflammatory cell-mediated response to the non-biodegradable f-GBN. The GF ' in vivo test-tube'system together with blood sampling provided unique insight into the time-course, qualitative, and quantitative aspects of immune system activities initiated by the presence of f-GBN in a complex tissue of a living animal. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Plant secondary compounds are diverse structurally, and associated biological effects can vary depending on multiple factors including chemical structure and reaction conditions. Phenolic compounds such as tannins can chelate dietary iron, and supplementation of animal species sensitive to iron overload with tannins may prevent/treat iron overload disorder. We assessed the nutrient and phenolic composition and iron-binding capacity of Carolina willow (Salix caroliniana), a plant fed to zoo-managed browsing herbivores. Based on studies in other plant species and the chemical structures of phenolic compounds, we hypothesized that the concentration of condensed tannins in willow would be inversely related to the concentration of phenolic glycosides and directly related to iron-binding capacity. Our results indicated that willow nutrient composition varied by year, season, and plant part, which could be taken into consideration when formulating animal diets. We also found that the predominant plant secondary compounds were condensed tannins with minimal phenolic glycosides. Instead of binding to iron, the willow leaf extracts reduced iron from the ferric to ferrous form, which may have prooxidative effects and increase the bioavailability of iron depending on animal species, gastrointestinal conditions, and whole animal processes. We recommend identifying alternative compounds that effectively chelate iron in vitro and conducting chelation therapy trials in vivo to assess potential effects on iron balance and overall animal health. Zoo Biol. [ABSTRACT FROM AUTHOR]

Urolith formation has been documented in giraffes and goats. As research in giraffes poses logistical challenges, 16 buck goats were used as a model. The impact of two commercially available, pelleted feeds used for giraffes, ADF-16 and Wild Herbivore (WH), as well as the impact of alfalfa hay and pellet proportions (20% hay:80% pellets, 80P or 80% hay:20% pellet, 20P) on the formation of urolithogenic precursors in goat urine was accomplished in a 2 × 2 factorial balance study. Complete diets contained 0.60, 0.32, 0.35 and 0.26% phosphorus (P) with calcium:P ratios of 1.60, 4.16, 3.06 and 5.23, for 80P-ADF-16, 20P-ADF-16, 80P-WH and 20P-WH respectively. Total faeces and urine were collected over two 5-day periods to assess N and mineral balance. Fresh urine samples were collected and evaluated microscopically for urolithic crystal content. Urinary nitrogen (N) was lower and N retention was higher in goats fed 80P diets (p < 0.05). Intake of P was greatest for goats fed 80P-ADF-16; however, urinary P excretion and P retention were not affected by treatment. Crystal scores were higher in animals receiving 80P diets (p = 0.08), with crystals being composed predominantly of calcium phosphate. Urine pH was alkaline (>8) for all treatments. Urinary P concentration, a risk factor for urolithiasis, was highest (p ≤ 0.06) in the 80P-ADF-16 treatment (0.38 vs. 0.01, 0.02 and 0.04 mg/dl for 20P-ADF-16, 80P-WH and 20P-WH respectively), reflecting its highest dietary P level. Further investigation is recommended to determine the long-term effects of these diets on urolithogenic compound formation. [ABSTRACT FROM AUTHOR]

Background: Dyskeratosis Congenita (DKC) is a syndrome characterized by immunodeficiency, bone marrow failure, somatic abnormalities, and cancer predisposition resulting from defective telomere maintenance. The immunologic features of DKC remain under diagnosed and under treated despite the fact that immunodeficiency is a major cause of premature mortality in DKC. Methods: This study undertook a retrospective review of 7 DKC patients diagnosed at the Children's Hospital of Philadelphia. In parallel, we reviewed previously reported immunologic findings in DKC patients. Results: Immunologic abnormalities (lymphopenia, low B-cell numbers, hypogammaglobulinemia, and decreased T-cell function) were the most frequent laboratory findings at initial presentation, preceding the development of significant anemia or thrombocytopenia. Recurrent sinopulmonary or opportunistic infections were present in 6/7 patients. Infant-onset patients had more severe immunologic and somatic features (particularly severe enteropathy). Conclusion: In DKC, development of immunologic abnormalities can precede bone marrow failure, highlighting the importance of proper immunodeficiency management to minimize morbidity and premature mortality in this disease. [ABSTRACT FROM AUTHOR]

Background and purpose: As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT1A receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT1A receptor antagonist activities, was evaluated in preclinical models. Experimental approach: Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models. Key results: WAY-211612 inhibited 5-HT reuptake (Ki = 1.5 nmol·L−1; KB = 17.7 nmol·L−1) and exhibited full 5-HT1A receptor antagonist activity (Ki = 1.2 nmol·L−1; KB = 6.3 nmol·L−1; Imax 100% in adenyl cyclase assays; KB = 19.8 nmol·L−1; Imax 100% in GTPγS). WAY-211612 (3 and 30 mg·kg−1, po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT1A receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3–30 mg·kg−1, po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg·kg−1, s.c.) and a 5-HT1A antagonist (WAY-100635; 0.3 mg·kg−1, s.c). WAY-211612 (3.3–30 mg·kg−1, s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3–30 mg·kg−1, i.p. and 10–56 mg·kg−1, po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg·kg−1, i.p.) in the rat scheduled-induced polydipsia model. Conclusions and implications: These findings suggest that WAY-211612 may represent a novel antidepressant. [ABSTRACT FROM AUTHOR]

Debate continues as to why executive function (EF) continues to show impairments in children with early and continuously treated phenylketonuria (ECT-PKU). Using a mixed model, we measured EF in 10 adolescent children with ECT-PKU and 6 sibling controls, and examined associations between EF and (1) phenylalanine (phe) and (2) the phenylalanine : tyrosine ratio (phe : tyr). Measurements were taken on two occasions anticipated to yield variation in concurrent biochemistry resulting from changes in dietary compliance (i.e. holiday vs non-holiday period). A repeated measuresanova using the Behaviour Rating Inventory of Executive Function yielded the following results: no significant interactions; two significant group effects of substantially impaired working memory and initiation skills in children with ECT-PKU compared with controls, irrespective of occasion and two significant time effects, suggestive of slightly poorer non-holiday planning and organization scores in both groups. Further analyses revealed that phe levels were not significantly different on these occasions, suggesting that holiday dietary compliance may be better than expected. Correlations between EF and biochemistry in children with PKU showed that participant’s lifetime phe : tyr ratio was positively and significantly associated with EF impairment, more so than phe-only measures. [ABSTRACT FROM AUTHOR]

Aim. This paper is a report of a study to explore the changes and challenges to patients' lifestyles following treatment for head and neck cancer. Background. Head and neck cancer affects some of the most basic aspects of daily functioning, such as eating and speaking. There has been a rapid increase in the number of studies on the quality of life for people with head and neck cancer, but most studies have used quantitative methodology. Methods. Using a qualitative approach, data were collected in 2004 using semi-structured interviews with a purposive sample of 10 participants who had completed treatment 6-12 months earlier for head and neck cancer. A thematic analysis was employed to interpret the findings. Findings. Following thematic analysis seven broad themes were identified, five of which covered areas of changes and challenges to participants' lifestyles following treatment. These were: physical changes, concerns about cancer, work and day-to-day tasks, interpersonal relationships and social functioning. The concerns and challenges experienced following treatment were not limited to one aspect of an individual's lifestyle but spanned a number of the themes identified, highlighting the complexity of needs following treatment for head and neck cancer. The other two themes concerned personal attributes that facilitated or inhibited posttreatment coping and specific information needs in the posttreatment period. Conclusion. Specific posttreatment concerns and challenges cannot be viewed as unitary or discrete aspects of life, but should be considered within a biopsychosocial context, to address patients' needs holistically. [ABSTRACT FROM AUTHOR]

Summary Reasons for performing study: Common methods used to treat back problems in horses need to be assessed objectively. Objectives: To measure spinal mechanical nociceptive thresholds (MNTs) and evaluate the effects of chiropractic, massage and phenylbutazone, compared with active and inactive control groups. Methods: Baseline MNTs at 7 sites within the thoracolumbar and sacral regions were measured in 38 healthy mature horses exhibiting no clinical signs of lumbar pain. Horses were assigned to one of 3 treatment groups: instrumentassisted chiropractic treatment, therapeutic massage and phenylbutazone; or 2 control groups: ridden exercise (active control) or routine paddock turnout with no ridden exercise (inactive control). MNT measurements were repeated at 1, 3 and 7 days post treatment. The percentage change from baseline MNT values was calculated within groups. Results: On Day 7, the median MNT had increased by 27, 12 and 8% in the chiropractic, massage and phenylbutazone groups, respectively. MNT changes of <1% were seen within the active and inactive control groups. Conclusions: Chiropractic treatment and massage therapy increased spinal MNTs within horses not exhibiting signs of lumbar pain. Potential relevance: Pressure algometry provides an objective tool to evaluate the effects of commonly used, but currently unproven treatment modalities on spinal MNTs. Future studies need to evaluate combined treatment effects and longer-term MNT changes in horses with documented back pain. [ABSTRACT FROM AUTHOR]

Aim. This paper is a report of a study to explore patients' experiences of having chemotherapy in a day hospital. Background. The nature of cancer care has changed dramatically in recent years with most patients receiving chemotherapy in a day hospital. Despite recognition of the need to explore patients' experience of cancer treatment, little research has been undertaken in this specific area. Method. A qualitative approach was adopted with a convenience sample of 30 patients diagnosed with cancer and receiving chemotherapy in a day hospital. Data were collected from January 2002 to March 2003 using unstructured tape-recorded interviews and analysed using a narrative framework. Findings. Participants viewed their experiences of chemotherapy treatment from the initial perspective of having to face their need to have chemotherapy. Their experiences in the day hospital had both positive and negative dimensions. Positive aspects related to maintaining a sense of normality and absence of the sick role, whilst negative aspects were related to the dehumanizing, factory-like system in the day hospital. Organizational issues also influenced experiences, including the sense of comradeship with other patients. Participants indicated the need to remain positive about the future and to learn to 'work around' the treatment. Conclusion. More effective methods are needed to develop patients' confidence and motivation to realize their self-care potential, together with increased awareness of organizational influences on patient experiences. Nurses need to focus on the 'here and now' concerns of patients as opposed to a biomedical perspective relating to treatment regimes, survival and prognosis. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AIMS AND OBJECTIVES: This study sought to explore the nurses' experience of a day hospital chemotherapy service in an acute general hospital in Northern Ireland and how this compared with their experience of working in an inpatient setting. BACKGROUND: Despite the many changes taking place in cancer care delivery, little research has been conducted on nurses' experience of working in more acute cancer treatment settings. Research conducted to date has tended to focus on the role of nurses in wards, hospices and palliative care settings. DESIGN: This Heideggerian hermeneutic phenomenological study explored nurses' lived experience of day hospital chemotherapy service. METHOD: Face-to-face focused in-depth interviews were conducted with the total population of nurses who worked in the day hospital at the time of data collection (n = 10). Data analysis involved a two-staged approach, the analysis of narratives and narrative analysis, based on the work of Polkinghorne (1995). CONCLUSIONS: The nurses' viewed their experience of the chemotherapy day hospital as having both positive and negative dimensions. The positive dimensions included an increased sense of autonomy and the challenge of developing new skills, while the negative dimension included a perceived decrease in their caring role: (i) The individual characteristics of the nurse were seen to have a key influence on caring experience; (ii) Role changes led to a perceived dichotomy between their actual and aspired role and their caring and clinical role. RELEVANCE TO CLINICAL PRACTICE: There is a need to achieve a balance between delivering a clinical role (administering chemotherapy) while maintaining the centrality of the nurse-patient relationship. This can be likened to achieving a balance between 'nursing the clinic' alongside 'nursing the patient'. These findings have implications for the discourse on caring within other outpatient type clinics and discourse on cancer nursing as therapy and the culture of the cancer clinic. [ABSTRACT FROM AUTHOR]

AIM: This paper reports a study exploring district nurses' experiences of providing palliative care for patients with cancer and their families. BACKGROUND: There is an increasing demand for palliative care in the community, as many patients wish to die at home. District nurses are central to providing palliative care in the community, but there is a dearth of literature on district nurses' experiences in palliative care. METHOD: A Husserlian phenomenological approach was adopted with a purposive sample of 25 female district nurses. Data were collected using unstructured, tape-recorded interviews and analysed using Colaizzi's seven stages of data analysis. FINDINGS: Four themes were identified: the communication web; the family as an element of care; challenges for the district nurse in symptom management and the personal cost of caring. CONCLUSIONS: District nurses' experiences of providing palliative care to family units was challenging but rewarding. The emotive nature of the experience cannot be under-estimated, as many district nurses were touched by the varying situations. Whilst acknowledging the need to maintain an integrated approach to care, district nurses should be identified as the key workers in the complex situation of palliative care. [ABSTRACT FROM AUTHOR]

Diabetic peripheral polyneuropathy is characterized by axonal degeneration and regeneration as well as by Schwann cell and microvascular changes. These changes have been described at both the light (LM) and the electron microscopic (EM) levels; however, EM has not been applied to large clinical trials. Our goal was to adapt the rigorous techniques used for quantifying human biopsies with LM image analysis to accommodate ultrastructural analyses. We applied digital image capture and analysis to the ultrastructural examination of axons in sural nerve biopsies from diabetic patients enrolled in a multicenter clinical trial. The selection of sural nerve biopsies was based on the quality of specimen fixation, absence of physical distortion, and nerve fascicle size (≥100 000; ≤425 000 µm2). Thin sections were collected on formvar-coated slot grids, stabilized with carbon and scanned on a Phillips CM100 transmission electron microscope. Digital images were captured with a Kodak Megaplus 1.6 camera. A montage was constructed using software derived from aerial mapping applications, and this virtual image was viewed by EM readers. Computer-assisted analyses included identification and labeling of individual axons and axons within regenerating clusters. The average density of regenerating myelinated axon clusters per mm2 was 65.8 ± 5.1, range of 0–412 ( n = 193). These techniques increase the number of samples that may be analyzed by EM and extend the use of this technique to clinical trials using tissue biopsies as a primary endpoint. [ABSTRACT FROM AUTHOR]

Background: Post partum hemorrhage is a major cause of maternal death, particularly in developing countries, and most cases are due to an atonic uterus. Hemorrhage can occur despite active management of the third stage of labor. Presently, misoprostol (Cytotec, Searle Pharmaceuticals) is the only thermostable uterotonic agent potentially available which would be economically beneficial for developing countries where refrigeration of drugs poses a problem. The objective of the study was to compare intra-muscular Syntometrine (Sandoz Pharmaceuticals) (ampoule=5 iu oxytocin and 500 mcg ergometrine maleate) plus Syntocinon (Sandoz Pharmceuticals) (10 iu oxytocin diluted in 500 ml normal saline) intravenous infusion versus 800 mcg misoprostol per rectum for treatment of primary post partum hemorrhage in a developing country.Methods: Randomized single blinded two-center study, set in both a township and teaching hospital in South Africa. Sixty-four women with primary post partum hemorrhage due to an atonic uterus were recruited. The primary outcome measure was whether the hemorrhage ceased within 20 minutes of administering the first line treatment, once hemorrhage was clinically recognized.Results: There was a 28.1% difference between the misoprostol arm and the Syntometrine and Syntocinon arm (p=0.01). This result had a greater than 80% power. Misoprostol performed better.Conclusion: 800 mcg misoprostol per rectum is effective at treating primary post partum hemorrhage. [ABSTRACT FROM AUTHOR]

Abstracts Aims Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. Methods After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas–liquid chromatography/mass spectrometry. Results Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) μV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6) μV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) μV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4076 (1091) vs. 5219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Conclusions Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density). [ABSTRACT FROM AUTHOR]

A qualitative descriptive study was developed to gain an insight into the experiences of patients with operable cancer of the oesophagus and the information they received. Through semistructured interviews, participants related details about different aspects of information-giving. Key sources of information were the consultant surgeon and other patients. Nurses, other medical staff, physiotherapists and dieticians were then mentioned. Family/friends were poor sources. Positive and negative aspects of the verbal and written information given were described, but there was minimal support for audiovisual information. Participants were given information relating to a number of key areas: treatment details, side-effects, extent of their disease, cure and prognosis and return to normality. A number of problem areas were identified. The findings indicate a need for a thoracic nurse specialist, updating of the information booklet and development of a staff education programme. [ABSTRACT FROM AUTHOR]

The importance of information giving has been recognized and promoted in political, ethical and professional arenas and this has ultimately resulted in the publication of a vast amount of literature relating to the subject. This literature review considers the functions of patient information and the factors influencing information seeking for patients who have been diagnosed with cancer. Methods of providing information are discussed and the nurse's role in information giving is examined. A number of core problems are highlighted in relation to information giving. These problems, and possible reasons for them, are subsequently critically analysed. Finally, the literature relating to information needs of patients with cancer is evaluated and five key needs identified. [ABSTRACT FROM AUTHOR]

Discusses the identification of individuals with genetically determined deficiencies of complement. Infections with bacteria for which opsonization is the primary host defense; Differences between the rheumatic disorders seen in complement deficient patients and their counterparts in non-complement deficient patients; Mechanisms by which the complement system can participate in the processing and/or clearance of soluble immune complexes.

INTRODUCTION: Abnormal anatomy and complex electrophysiology in patients with Ebstein's anomaly of the tricuspid valve may confound attempts at radiofrequency ablation (RFA). METHODS AND RESULTS: Data for 65 pediatric Ebstein's patients (9.8+/-5.4 years, 4 months to 20 years; 39+/-25 kg, 5.1 to 108 kg) were obtained from the Pediatric Radiofrequency Ablation Registry. The degree of tricuspid regurgitation (DOTR) and the degree of Ebstein's anomaly were assessed with echocardiography/Doppler. Leading indications were drug refractoriness (24 [37%] of 65 patients) and life-threatening arrhythmia (14 [22%] of 65 patients). For the 65 patients, 82 typical (nondecremental) accessory pathways (APs) (62% right free wall, 34% right septal, and 4% left sided), 17 other supraventricular tachycardias (1 ectopic atrial, 7 AV reentry, 5 Mahaim, and 4 intra-atrial reentry tachycardias), and 1 ventricular mechanism were mapped. Thirty-four (52%) of 65 patients had a single AP (21 right free wall, 10 septal, and 3 left); 19 (29%) of 65 patients multiple APs; 6 (9%) of 65 patients a single AP plus a non-AP mechanism; and 6 (9%) of 65 patients non-AP mechanism(s) only. RFA acute success rates and recurrence rates for right free wall, right septal, and other mechanisms were 79%/32%, 89%/29%, and 75%/27%. Mild DOTR and a body surface area (BSA) < or = 1.7 m2 independently predicted a better acute success rate. BSA < or = 1.7 m2 also predicted long-term success. CONCLUSION: In this patient subset, life-threatening arrhythmias and multiple electrophysiologic mechanisms are commonly encountered during RFA. Mild DOTR and a BSA < or = 1.7 m2 predict a higher acute success rate. While acute success rates are relatively high, recurrence is frequent. [ABSTRACT FROM AUTHOR]

Chronic meningococcemia represents an uncommon manifestation of meningococcal disease. Microbial and host factors which may predispose to this form of meningococcal disease are not understood. Although acute meningococcal disease is frequently found in patients with terminal complement deficiencies, the relationship of chronic meningococcemia to complement deficiencies is unclear. We present a case report and a review of the literature describing chronic meningococcemia in association with deficiencies of the complement system. A total of eight cases were identified, all of whom were male. Six of the eight patients were children and two of the eight had a previous history of meningococcal disease. This case report, in conjunction with the previously reported cases, suggests an association between complement deficiencies and chronic meningococcemia. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented with respect to the interest in alternative glycaemic markers such as fructosamine which has been rekindled due to increasing data on their ability to improve diagnosis and predict onset and complications of diabetes.

The pathophysiology of diabetic neuropathy (DN) is complex involving both metabolic and vascular deficits. Recent data have implicated a potential role for programmed cell death (PCD) in the development of experimental DN (EDN). Oxidative stress has emerged as a leading candidate in the development of nerve blood flow (NBF) and nerve conduction deficits. We have previously shown that replacement of the endogenous antioxidant taurine in the nerve of streptozotocin-diabetic (STZ-D) rats corrects neuro-vascular dysfunction, prevents deficits in Na,K-ATPase activity and attenuates motor and sensory NCV slowing. The aims of this study were to examine the hypothesis that oxidative stress-mediated mitochondrial dysfunction may promote the activation of PCD pathways in STZ-D rats and to determine whether these effects could be attenuated by taurine. Dorsal root ganglion (DRG) neurons were extracted from perfused control (C), STZ-D and STZ-D rats given a 1% taurine supplemented diet for 6 weeks. STZ-D induced a significant decrease in sensory nerve conduction velocity (SNCV) and NBF vs controls and these deficits were corrected by taurine. Lumbar and sacral DRG were sectioned at 10 mm intervals and slides were prepared from two different sampling sites. Apoptosis was detected by TUNEL staining. 150 or more DRG nuclei were counted per animal. In STZ-D rats 21.3 ± 4.9% of DRG nuclei were found to be TUNEL positive as compared with 2.9 ± 2.1% in controls (p < 0.05). Taurine replacement markedly attenuated apoptosis since only 6.5 ± 2.9% neurons were TUNEL positive. In summary, 6 weeks of STZ-D increased apoptosis in DRG neurons of STZ-D rats. This increase in apoptosis could be prevented by replacement of the endogenous antioxidant taurine, implicating a role of taurine depletion in the development of sensory neuron degeneration. [ABSTRACT FROM AUTHOR]

Purpose: To describe current management of hospital-based trauma care in Timor-Leste from both a national and clinical perspective and evaluate the use of the WHO Essential Trauma Care Guidelines (EsTCG). Methodology: Nationwide mixed-methods study consisting of 3 stages. Stage 1 consisted of 5 in-depth interviews with Ministry of Health officials. Stage 2 involved quantitative audits of all 6 hospital facilities in Timor-Leste, supplemented by 25 semi-structured interviews with administrative and clinical staff involved in trauma care. During Stage 3, results from Stage 2 were presented to participants and findings discussed. Likert scale evaluation of the process was then completed by stage 2 participants to ascertain the value of the EsTCG in Timor-Leste. Results: Interviews revealed that while some elements of a trauma systems approach were present, there was no national coordination. At the hospital level, limited human resources and lack of organized approaches to trauma care severely impacted upon injury management. The audit suggested that while necessary equipment was often present, commonly it was not in working order, and specific weaknesses in capabilities for rehabilitation and blood transfusion were also noted. Participants generally felt that the EsTCG were effective in identifying these deficiencies and possible solutions. Conclusion: The EsTCG were useful in identifying national and clinical weaknesses in trauma care and may provide a framework for trauma system development in the future. However, the local context must be considered before applying recommendations in standard guidelines such as the EsTCG to ensure a “one size fits all” approach does not ensue. [ABSTRACT FROM AUTHOR]

. [ABSTRACT FROM AUTHOR]

Differential genotypic tolerance of two species of fish native to the Great Plains of North America (the western mosquitofish [Gambusia affinis] and the sand shiner [Norropis ludibundus]) was examined in 96-h acute exposures to the pesticides lindane and parathion. Although a significant amount of data is available indicating that heavy metals cause selective genotypic mortality in aquatic organisms, very few studies have focused on the effects of pesticides on population genetic structure. Fish used in this experiment were captured from field populations in Kansas, USA, and acclimated to laboratory conditions for I month before the acute toxicity tests. Two hundred individuals ofeach species were exposed, in two separate experiments, to estimatedLC70 concentrations of each pesticide for 96 h. Dead individuals were removed at 3-h intervals allowing for comparison of genotypic times-to-death. Individuals of each species were electrophoretically examined at two polymorphic loci. Phenotypes of mosquitofish were determined for phosphoglucose mutase (PGM) and malic enzyme (ME). Phenotypes of sand shiners were determined for PGM and aspartate aminotransferase (AAT). Three of eight statistical tests (two species X two loci X two pesticides) indicated significant differences among survival curves of genotypic classes. Genotypes of ME and PGM of mosquitofish exhibited significantly different survivorship functions in the parathion and lindane time-to-death tests, respectively. Genotypes of AAT of sand shiners exhibited significantly different survivorship curves whenexposed to lindane. Given certain experimental limitations, these results support a continued examination of population genetic characteristics as biomarkers of environmental contamination. [ABSTRACT FROM AUTHOR]

Two species of fishes common to the Great Plains of North America (the western mosquitofish [Gambusia affinis] and the sand shiner [Norropis ludibundus]) were used to examine the relationship between individual time-to-death (TTD) in 96-h toxicity tests and average fluctuating asymmetry (FA). Previous studies have indicated that FA, the random deviation from bilateral symmetry in metric traits, is increased inorganisms that develop in stressful and/or marginal environments. This association has led to the prediction that FA may be useful as a bioindicator. For example, if an individual's FA is negatively relatedto stress resistance, a population that has comparatively high values of FA may be more susceptible to further stressors. Adult fish usedin these experiments were captured from natural populations in Kansas and acclimated to laboratory conditions for I month before use in toxicity tests. Each species was separately exposed to two insecticides: parathion, an organophosphate, and lindane, an organochlorine. Foreach TTD test, 200 individuals were exposed over a 96-h period to anLC70 concentration. Dead individuals were removed every 3 h. Individuals that survived the test were sacrificed f6r comparison to those that died. Measurements for seven external morphologic characters wereobtained for each individual and used to estimate average FA. Three of four statistical tests showed a significant negative regression between TTD and average FA, indicating that individuals with smaller FAsurvived longer in the test conditions. These results support the use of FA as an indicator of susceptibility to pesticides. [ABSTRACT FROM AUTHOR]