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1.
Cancer Res ; 83(2): 167-169, 2023 01 18.
Article in English | MEDLINE | ID: mdl-36651076

ABSTRACT

While the goal of most anticancer treatments is to kill cancer cells, some therapies halt cancer progression by inducing cancer cell differentiation. For example, retinoic acid induces neuroblastoma cell differentiation in vitro and is used as maintenance therapy for children with high-risk neuroblastoma. A new study by Jiang and colleagues has revealed the mitochondrial uncoupler niclosamide ethanolamine (NEN) induces neuroblastoma cell differentiation in vitro and slows neuroblastoma tumor growth in vivo. Mitochondrial uncoupler molecules alter cell metabolism by forcing cells to "burn" more nutrients, resulting in a switch from anabolic to catabolic metabolism. NEN-induced neuroblastoma cell differentiation was associated with disruption of Warburg metabolism, epigenetic remodeling, and downregulation of key oncogenic drivers of neuroblastoma development, including MYCN. NEN is currently used as an antiparasitic worm treatment and is safe to use in children but has poor pharmacokinetic properties. However, derivatives of NEN and structurally distinct uncouplers that have improved pharmacokinetic properties are in development. Results of this study ignite the idea that mitochondrial uncouplers could be used as differentiating agents and expand the pharmacotherapy toolkit to treat cancer, including neuroblastoma. See related article by Jiang et al., p. 181.


Subject(s)
Antineoplastic Agents , Neuroblastoma , Humans , Epigenome/drug effects , Antineoplastic Agents/pharmacology , Tretinoin/pharmacology , Cell Differentiation/drug effects , Niclosamide/pharmacology , Ethanolamine/pharmacology , Ethanolamine/therapeutic use , Neuroblastoma/pathology
2.
Ir J Psychol Med ; 37(2): 122-125, 2020 06.
Article in English | MEDLINE | ID: mdl-32638668

ABSTRACT

A 57-year-old female patient with a diagnosis of schizo-affective disorder since 1986 was commenced on clozapine due to persistent positive and negative psychotic symptoms in September 2014. After commencement of clozapine she was delusion free and demonstrated an improvement in negative symptoms. Three months after commencement of clozapine she developed a hypersensitivity reaction. Her symptoms continued to deteriorate despite being prescribed an anti-histamine. Clozapine was discontinued 6 days after the appearance of a generalised pruritic rash, as it was believed to be the probable cause. There was complete resolution of symptoms 1 week after discontinuation of clozapine. Clozapine was replaced with olanzapine and amisulpride. There has been no similar cutaneous or allergic reactions for the past 30 months.


Subject(s)
Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Drug Hypersensitivity , Psychotic Disorders/drug therapy , Female , Humans , Middle Aged
3.
Ir J Psychol Med ; 37(2): 77-88, 2020 06.
Article in English | MEDLINE | ID: mdl-32638671

ABSTRACT

OBJECTIVES: To examine the delivery and assessment of psychiatry at undergraduate level in the six medical schools in the Republic of Ireland offering a medical degree programme. METHODS: A narrative description of the delivery and assessment of psychiatry at undergraduate level by collaborative senior faculty members from all six universities in Ireland. RESULTS: Psychiatry is integrated to varying degrees across all medical schools. Clinical experience in general adult psychiatry and sub-specialities is provided by each medical school; however, the duration of clinical attachment varies, and the provision of some sub-specialities (i.e. forensic psychiatry) is dependent on locally available resources. Five medical schools provide 'live' large group teaching sessions (lectures), and all medical schools provide an array of small group teaching sessions. Continuous assessment encompasses 10-35% of the total assessment marks, depending on the medical school. Only one medical school does not provide a clinical examination in the form of an Objective Structured Clinical Examination with viva examinations occurring at three medical schools. CONCLUSIONS: Many similarities exist in relation to the delivery of psychiatry at undergraduate level in Ireland. Significant variability exists in relation to assessment with differences in continuous assessment, written and clinical exams and the use of vivas noted. The use of e-learning platforms has increased significantly in recent years, with their role envisaged to include cross-disciplinary teaching sessions and analysis of examinations and individual components within examinations which will help refine future examinations and enable greater sharing of resources between medical schools.


Subject(s)
Curriculum , Education, Medical, Undergraduate , Psychiatry/education , Schools, Medical , Humans , Ireland
4.
J Hosp Infect ; 103(2): 200-209, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31077777

ABSTRACT

BACKGROUND: The National Health Service in England advises hospitals collect data on hospital-onset diarrhoea (HOD). Contemporaneous data on HOD are lacking. AIM: To investigate prevalence, aetiology and management of HOD on medical, surgical and elderly-care wards. METHODS: A cross-sectional study in a volunteer sample of UK hospitals, which collected data on one winter and one summer day in 2016. Patients admitted ≥72 h were screened for HOD (definition: ≥2 episodes of Bristol Stool Type 5-7 the day before the study, with diarrhoea onset >48 h after admission). Data on HOD aetiology and management were collected prospectively. FINDINGS: Data were collected on 141 wards in 32 hospitals (16 acute, 16 teaching). Point-prevalence of HOD was 4.5% (230/5142 patients; 95% confidence interval (CI) 3.9-5.0%). Teaching hospital HOD prevalence (5.9%, 95% CI 5.1-6.9%) was twice that of acute hospitals (2.8%, 95% CI 2.1-3.5%; odds ratio 2.2, 95% CI 1.7-3.0). At least one potential cause was identified in 222/230 patients (97%): 107 (47%) had a relevant underlying condition, 125 (54%) were taking antimicrobials, and 195 (85%) other medication known to cause diarrhoea. Nine of 75 tested patients were Clostridium difficile toxin positive (4%). Eighty (35%) patients had a documented medical assessment of diarrhoea. Documentation of HOD in medical notes correlated with testing for C. difficile (78% of those tested vs 38% not tested, P<0.001). One-hundred and forty-four (63%) patients were not isolated following diarrhoea onset. CONCLUSION: HOD is a prevalent symptom affecting thousands of patients across the UK health system each day. Most patients had multiple potential causes of HOD, mainly iatrogenic, but only a third had medical assessment. Most were not tested for C. difficile and were not isolated.


Subject(s)
Cross Infection/epidemiology , Cross Infection/etiology , Diarrhea/epidemiology , Diarrhea/etiology , Disease Management , Aged , Aged, 80 and over , Cross Infection/diagnosis , Cross Infection/therapy , Cross-Sectional Studies , Diarrhea/diagnosis , Diarrhea/therapy , England/epidemiology , Female , Hospitals , Humans , Male , Prevalence , Prospective Studies
5.
Oncogene ; 36(4): 501-511, 2017 01 26.
Article in English | MEDLINE | ID: mdl-27321182

ABSTRACT

Neuroblastoma, the most common solid tumor of young children, frequently presents with aggressive metastatic disease and for these children the 5-year survival rates are dismal. Metastasis, the movement of cancer cells from one site to another, involves remodeling of the cytoskeleton including altered microtubule dynamics. The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblastoma metastasis although precise functions remain poorly defined. In this study we investigated stathmin's contribution to the metastatic process and potential mechanism(s) by which it exerts these effects. Stathmin suppression significantly reduced neuroblastoma cell invasion of 3D tumor spheroids into an extracellular matrix. Moreover, inhibiting stathmin expression significantly reduced transendothelial migration in two different neuroblastoma cell lines in vitro. Inhibition of ROCK, a key regulator of cell migration, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through ROCK signaling. Reduced stathmin expression in neuroblastoma cells significantly increased the activation of the RhoA small GTPase. Notably, re-expression of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding returned cell migration and transendothelial migration back to control levels, indicating that stathmin may influence these processes in neuroblastoma cells independent of tubulin binding. Finally, stathmin suppression in neuroblastoma cells significantly reduced whole body, lung, kidney and liver metastases in an experimental metastases mouse model. In conclusion, stathmin suppression interferes with the metastatic process via RhoA/ROCK signaling in neuroblastoma cells. These findings highlight the importance of stathmin to the metastatic process and its potential as a therapeutic target for the treatment of neuroblastoma.


Subject(s)
Neuroblastoma/pathology , Stathmin/antagonists & inhibitors , rho-Associated Kinases/metabolism , rhoA GTP-Binding Protein/metabolism , Animals , Cell Line, Tumor , Heterografts , Humans , Male , Mice , Mice, SCID , Neoplasm Metastasis , Neuroblastoma/metabolism , Signal Transduction , Stathmin/biosynthesis , Transendothelial and Transepithelial Migration , Transfection , Tubulin/metabolism
6.
Ir J Psychol Med ; 34(2): 117-126, 2017 Jun.
Article in English | MEDLINE | ID: mdl-30115215

ABSTRACT

OBJECTIVES: To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid levels are associated with episodes of self-harm or depression over a 10-year period. METHODS: We included 40 individuals who self-harmed and 40 controls. Episodes of self-harm and depression were ascertained and levels of depression, impulsivity, suicidal ideation and plasma lipid levels measured at baseline and at 10-year follow-up. RESULTS: Further episode(s) of self-harm occurred in 26% of cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm episodes. Baseline eicosapentaenoic acid levels were modestly correlated with suicidal ideation at follow-up and dihomo-γ-linolenic acid and arachidonic acid were modestly correlated with motor impulsivity at follow-up in cases. CONCLUSIONS: Despite significant negative correlations at baseline between plasma lipids, n-3 PUFAs and psychopathology, these levels were not predictive of clinical outcome over a 10-year period. Further research however is required due to the relatively low sample size and the risk of selection bias due to loss to follow-up in this study.

7.
Environ Entomol ; 44(3): 789-97, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26313985

ABSTRACT

Vector control is widely viewed as an integral part of disease management. Yet epidemiological theory suggests that the effectiveness of control programs at limiting pathogen spread depends on a variety of intrinsic and extrinsic aspects of a pathosystem. Moreover, control programs rarely evaluate whether reductions in vector density or activity translate into reduced disease prevalence. In areas of California invaded by the glassy-winged sharpshooter (Homalodisca vitripennis Germar), Pierce's disease management relies heavily on chemical control of this vector, primarily via systemic conventional insecticides (i.e., imidacloprid). But, data are lacking that attribute reduced vector pressure and pathogen spread to sharpshooter control. We surveyed 34 vineyards over successive years to assess the epidemiological value of within-vineyard chemical control. The results showed that imidacloprid reduced vector pressure without clear nontarget effects or secondary pest outbreaks. Effects on disease prevalence were more nuanced. Treatment history over the preceding 5 yr affected disease prevalence, with significantly more diseased vines in untreated compared with regularly or intermittently treated vineyards. Yet, the change in disease prevalence between years was low, with no significant effects of insecticide treatment or vector abundance. Collectively, the results suggest that within-vineyard applications of imidacloprid can reduce pathogen spread, but with benefits that may take multiple seasons to become apparent. The relatively modest effect of vector control on disease prevalence in this system may be attributable in part to the currently low regional sharpshooter population densities stemming from area-wide control, without which the need for within-vineyard vector control would be more pronounced.


Subject(s)
Hemiptera , Imidazoles , Insect Control , Insecticides , Nitro Compounds , Plant Diseases/prevention & control , Vitis , Agriculture , Animals , California , Neonicotinoids , Plant Diseases/microbiology , Vitis/growth & development
8.
Ultrasound Obstet Gynecol ; 46(6): 688-94, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25597867

ABSTRACT

OBJECTIVES: To assess whether severity of congenital diaphragmatic hernia (CDH) correlates with the degree of left heart hypoplasia and left ventricle (LV) output, and to determine if factors leading to abnormal fetal hemodynamics, such as compression and reduced LV preload, contribute to left heart hypoplasia. METHODS: This was a retrospective cross-sectional study of fetuses at 16-37 weeks' gestation that were diagnosed with CDH between 2000 and 2010. Lung-to-head ratio (LHR), liver position and side of the hernia were determined from stored ultrasound images. CDH severity was dichotomized based on LHR and liver position. The dimensions of mitral (MV) and aortic (AV) valves and LV were measured, and right and left ventricular outputs were recorded. RESULTS: In total, 188 fetuses with CDH were included in the study, 171 with left CDH and 17 with right CDH. Fetuses with severe left CDH had a smaller MV (Z = -2.24 ± 1.3 vs -1.33 ± 1.08), AV (Z = -1.39 ± 1.21 vs -0.51 ± 1.05) and LV volume (Z = -4.23 ± -2.71 vs -2.08 ± 3.15) and had lower LV output (26 ± 10% vs 32 ± 10%) than those with mild CDH. MV and AV in fetuses with right CDH (MV, Z = -0.83 ± 1.19 and AV, Z = -0.71 ± 1.07) were larger than those in fetuses with left CDH, but LV outputs were similarly diminished, regardless of hernia side. Severe dextroposition and abnormal liver position were associated independently with smaller left heart, while LHR was not. CONCLUSION: The severity of left heart hypoplasia correlates with the severity of CDH. Altered fetal hemodynamics, leading to decreased LV output, occurs in both right- and left-sided CDH, but the additional compressive effect on the left heart is seen only when the hernia is left-sided. Improved knowledge of the physiology of this disease may lead to advances in therapy and better risk assessment for use in counseling affected families.


Subject(s)
Fetal Development , Fetal Diseases/diagnostic imaging , Fetal Heart/diagnostic imaging , Hernias, Diaphragmatic, Congenital/embryology , Hypoplastic Left Heart Syndrome/embryology , Cross-Sectional Studies , Echocardiography/methods , Female , Fetal Heart/anatomy & histology , Gestational Age , Head/diagnostic imaging , Head/embryology , Heart Ventricles/diagnostic imaging , Heart Ventricles/embryology , Hernias, Diaphragmatic, Congenital/complications , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Humans , Hypoplastic Left Heart Syndrome/diagnostic imaging , Liver/diagnostic imaging , Liver/embryology , Lung/diagnostic imaging , Lung/embryology , Organ Size , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal/methods
9.
Eur Spine J ; 24 Suppl 1: S42-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25410160

ABSTRACT

PURPOSE: Pedicle subtraction osteotomy is a well-described surgical technique for treatment of kyphotic deformity in the spine. It is not widely used for treatment of thoracic kyphosis. We present the first documented series of 28 patients who underwent this procedure in 3 international centers. These patients presented with severe deformity with a wide range of aetiologies. INDICATIONS: Kyphosis larger than 70 degrees, which is demonstrably rigid based on dynamic imaging. MATERIALS AND METHODS: 28 patients underwent surgery following pre-op neurological and radiographic assessment to fully assess the deformity. A triangular osteotomy was carried out using intraoperative navigation techniques. The patients were assessed post-operatively again with clinical and radiographic parameters at regular follow-up. RESULTS: The mean ODI score after surgery was 24.7 (16-42) while the pre-op was 53.4 (38-76). Mean thoracic kyphosis was improved from 64.2° (±20.1°) to 41.1° (±17.4°) resulting in a mean sagittal correction of 23.1°. Mean segmental correction at the PSO for all 28 cases was 17.8° (±8.1°). Stratified by region we found different values for the PSO correction: between T1 and T5 (6 cases) it was 17.5° (±5.4°) and between T6 and T9 (4 cases) 18.2° (±4.7°) and between T10 and L1 (18 cases) 26.2° (±5.2°). FBI index was 22.3° pre-op and improved to 7.8° post-op. Calculations were performed with Microsoft excel (2011 Microsoft, Redmond, WA). CONCLUSIONS: Global sagittal balance was statistically improved in this series as demonstrated by FBI and C7 SVA correction.


Subject(s)
Kyphosis/surgery , Lumbar Vertebrae/surgery , Osteotomy/methods , Thoracic Vertebrae/surgery , Female , Follow-Up Studies , Humans , Kyphosis/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Patient Satisfaction , Postoperative Complications , Radiography , Retrospective Studies , Thoracic Vertebrae/diagnostic imaging , Visual Analog Scale
10.
Oncogene ; 33(7): 882-90, 2014 Feb 13.
Article in English | MEDLINE | ID: mdl-23396365

ABSTRACT

Metastatic neuroblastoma is an aggressive childhood cancer of neural crest origin. Stathmin, a microtubule destabilizing protein, is highly expressed in neuroblastoma although its functional role in this malignancy has not been addressed. Herein, we investigate stathmin's contribution to neuroblastoma tumor growth and metastasis. Small interfering RNA (siRNA)-mediated stathmin suppression in two independent neuroblastoma cell lines, BE(2)-C and SH-SY5Y, did not markedly influence cell proliferation, viability or anchorage-independent growth. In contrast, stathmin suppression significantly reduced cell migration and invasion in both the neuroblastoma cell lines. Stathmin suppression altered neuroblastoma cell morphology and this was associated with changes in the cytoskeleton, including increased tubulin polymer levels. Stathmin suppression also modulated phosphorylation of the actin-regulatory proteins, cofilin and myosin light chain (MLC). Treatment of stathmin-suppressed neuroblastoma cells with the ROCKI and ROCKII inhibitor, Y-27632, ablated MLC phosphorylation and returned the level of cofilin phosphorylation and cell invasion back to that of untreated control cells. ROCKII inhibition (H-1152) and siRNA suppression also reduced cofilin phosphorylation in stathmin-suppressed cells, indicating that ROCKII mediates stathmin's regulation of cofilin phosphorylation. This data demonstrates a link between stathmin and the regulation of cofilin and MLC phosphorylation via ROCK. To examine stathmin's role in neuroblastoma metastasis, stathmin short hairpin RNA (shRNA)\luciferase-expressing neuroblastoma cells were injected orthotopically into severe combined immunodeficiency-Beige mice, and tumor growth monitored by bioluminescent imaging. Stathmin suppression did not influence neuroblastoma cell engraftment or tumor growth. In contrast, stathmin suppression significantly reduced neuroblastoma lung metastases by 71% (P<0.008) compared with control. This is the first study to confirm a role for stathmin in hematogenous spread using a clinically relevant orthotopic cancer model, and has identified stathmin as an important contributor of cell invasion and metastasis in neuroblastoma.


Subject(s)
Lung Neoplasms/metabolism , Neuroblastoma/metabolism , RNA Interference , Stathmin/genetics , Actin Depolymerizing Factors/metabolism , Animals , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Shape , Cell Survival , Cytoskeleton/metabolism , Gene Knockdown Techniques , Humans , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Mice , Neoplasm Invasiveness , Neoplasm Transplantation , Neuroblastoma/genetics , Neuroblastoma/secondary , Phosphorylation , Protein Processing, Post-Translational , RNA, Small Interfering/genetics , Stathmin/metabolism , Tumor Burden , rho-Associated Kinases/antagonists & inhibitors , rho-Associated Kinases/metabolism
11.
Ir J Psychol Med ; 31(2): 143-148, 2014 Jun.
Article in English | MEDLINE | ID: mdl-30189514

ABSTRACT

Introduction We present the case of a 27-year-old man with a background diagnosis of treatment resistant schizophrenia and absent insight who for the last 3 years has been residing in a high support residential setting on approved leave under the Mental Health Act (MHA) 2001. The case demonstrates how this man achieved clinical stability in the community with the assistance of long-term involuntary admission under the MHA 2001, in contrast to the previous years of his illness in which he had suffered multiple relapses of his psychotic illness with ssociated distress, poor self-care and repeated in-patient re-admissions. We discuss the equivalent use of community treatment orders in other jurisdictions and how the judicious use of approved leave under the MHA 2001 may be used as an alternative in Ireland where community treatment orders are not currently available. METHOD: Case Report. CONCLUSION: The case report highlights how the use of long-term approved leave under the MHA2001 may be used as alternative in Ireland to mimic CTOs for certain difficult to treat patients with psychotic illness who would benefit from ongoing treatment, but lack capacity to engage in such treatment due to persistent symptoms and lack of insight.

12.
Injury ; 42 Suppl 5: S3-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22196908

ABSTRACT

We review prevention strategies to minimise the risk of MRSA soft tissue and bone infections, which can be devastating for the patient and costly for the healthcare provider. Department of Health (England) policy is that screening for emergency admissions will be mandatory from 2011, in addition to existent elective admission screening. Rapid screening technology has not been shown to be cost-effective, meaning that there will be a lag time between admission and the patient's MRSA status being known. Thus, standard infection control policies regarding isolation of high-risk patients will remain, with a continuing focus on MRSA decolonisation, aimed at minimising the risks of auto-infection and transmission to other patients. Antimicrobial prescribing policies should be designed to take into account the local burden of resistant organisms, but also minimise unnecessary antibiotic use. There is an increasing realisation that reducing the use of fluoroquinolones and third-generation cephalosporins (which have been associated with increased carriage of MRSA) in patient populations where MRSA is prevalent can be a useful control measure. Prevention of orthopaedic infections clearly involves general operating theatre protocols, such as suitable antiseptic skin preparation, and additional measures including the use of laminar airflow. Antibiotic prophylaxis is adjusted in patients known to have MRSA to include a glycopeptide, and local guidelines may adopt such regimens for all patients due to the burden of MRSA in the local patient population. A future development that may have an effect on practice is the development of a Staphylococcus aureus vaccine, which has been shown to be cost-effective in a computer-modelled evaluation.


Subject(s)
Carrier State/diagnosis , Infection Control/economics , Infection Control/methods , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/prevention & control , Anti-Bacterial Agents/therapeutic use , England , Guidelines as Topic , Humans , Mass Screening/economics , Patient Isolation/economics , Risk Factors
13.
J Econ Entomol ; 104(3): 868-78, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21735906

ABSTRACT

Healthy hemlock trees, Tsuga canadensis (L.) Carrière, and hemlock woolly adelgid, Adelges tsugae Annand (Hemiptera: Adelgidae), populations should favor retention and population growth of adelgid predators such as Laricobius nigrinus Fender (Coleoptera: Derodontidae) and Sasajiscymnus tsugae (Sasaji & McClure) (Coleoptera: Coccinellidae). Eastern hemlock trees between 15 and 38 cm diameter at breast height (dbh) were treated with 0, 10, or 25% of 1.5 g imidacloprid (Merit 75 WP) per 2.5 cm dbh and were either fertilized or not, in a 3 by 2 factorial design. After 2 yr, imidacloprid reduced the numbers of ovisacs and eggs found on trees in a dosage-dependent manner, while enhancing tree growth parameters such as new shoots or needles and the length of new shoots. Fertilized trees had greater adelgid fecundity, which was positively correlated with total foliar N in both winter generations. In February 2009 (27 mo after imidacloprid treatment), higher imidacloprid dosages to unfertilized trees resulted in reduced adelgid fecundity. Concentrations of N, P, and K were higher in the foliage of trees treated with insecticide, whereas foliar aluminum concentrations were consistently lower in trees with higher insecticide dosages. Trees treated with low rates of imidacloprid were healthier than untreated trees, but only trees treated with the 0.1 x dosage had sufficient adelgids to possibly sustain predators over extended periods.


Subject(s)
Fertilizers/analysis , Hemiptera/growth & development , Imidazoles/analysis , Insecticides/analysis , Nitro Compounds/analysis , Tsuga/growth & development , Animals , Coleoptera/physiology , Fertility , Food Chain , Georgia , Hemiptera/physiology , Insect Control , Metals/analysis , Neonicotinoids , Nitrogen/analysis , Phosphorus/analysis , Plant Leaves/chemistry , Population Density
14.
Ir J Med Sci ; 180(1): 185-9, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20924798

ABSTRACT

BACKGROUND: Farming is a major industry in the West of Ireland. This prospective study examined the age profile, nature and treatment of orthopaedic injuries occurring in agricultural surroundings presenting at the Orthopaedic Unit of Merlin Park Hospital, Galway. METHODS: The cohort consisted of 70 direct or indirect farm employees presenting with orthopaedic injuries caused in an accident occurring on a farm. RESULTS: There were significantly (P < 0.01) more male than female farmers (73 vs. 27%) with a mean age of 63 years (ranging from 13 to 87 years). Average number of out-patient visits related to the injury was 3.6. Injuries involving livestock resulted in the majority of accidents (P < 0.05) with a significant rise in the number of visits with increasing age (P < 0.01) with older patients having more severe injuries. Soft tissue injuries and fractures were commonly encountered. Complex fractures were the slowest injury to heal requiring eight subsequent out-patient visits.


Subject(s)
Agriculture , Musculoskeletal System/injuries , Musculoskeletal System/innervation , Accidental Falls/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Extremities/diagnostic imaging , Extremities/injuries , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Prospective Studies , Radiography , Wounds and Injuries/diagnostic imaging , Wounds and Injuries/epidemiology , Young Adult
15.
Clin Exp Immunol ; 163(1): 77-87, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21078085

ABSTRACT

B and T lymphocyte attenuator (BTLA) is an immunoglobulin superfamily member surface protein expressed on B and T cells. Its ligand, herpesvirus entry mediator (HVEM), is believed to act as a monomeric agonist that signals via the CRD1 of HVEM to inhibit lymphocyte activation: HVEM is also the receptor for lymphotoxin-α and LIGHT, which both bind in the CRD2 and CRD3 domains of the HVEM molecule, and for CD160 which competes with BTLA. We have shown that recombinant HVEM and a panel of different monoclonal antibodies specifically bind murine BTLA on both B and T cells and that some antibodies inhibit anti-CD3ε-induced T cell proliferation in vitro, but only when constrained appropriately with a putatively cross-linking reagent. The antibodies had no significant effect on in vitro T cell proliferation in a mixed lymphocyte reaction (MLR) assay nor on in vitro DO11.10 antigen-induced T cell proliferation. None of these antibodies, nor HVEM-Fc, had any significant effect on in vitro B cell proliferation induced by anti-immunoglobulin M antibodies (±anti-CD40) or lipopolysaccharide. We further elucidated the requirements for inhibition of in vitro T cell proliferation using a beads-based system to demonstrate that the antibodies that inhibited T cell proliferation in vitro were required to be presented to the T cell in a cis, and not trans, format relative to the anti-CD3ε stimulus. We also found that antibodies that inhibited T cell proliferation in vitro had no significant effect on the antibody captured interleukin-2 associated with the in vivo activation of DO11.10 T cells transferred to syngeneic recipient BALB/c mice. These data suggest that there may be specific structural requirements for the BTLA molecule to exert its effect on lymphocyte activation and proliferation.


Subject(s)
Antibodies, Monoclonal/immunology , B-Lymphocytes/immunology , Lymphocyte Activation , Receptors, Immunologic/antagonists & inhibitors , Receptors, Immunologic/immunology , T-Lymphocytes/immunology , Animals , CD3 Complex/immunology , CD40 Antigens/immunology , Cross-Linking Reagents/chemistry , Immunoglobulin M/immunology , Interleukin-2/blood , Interleukin-2/immunology , Lymphotoxin-alpha/immunology , Mice , Mice, Inbred BALB C , Receptors, Tumor Necrosis Factor, Member 14/immunology
16.
Ir J Med Sci ; 177(4): 347-53, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18841438

ABSTRACT

Despite the well-documented benefits, some countries have yet to agree on the establishment of a national joint register. A questionnaire study was undertaken to ascertain the opinions of the consultant orthopaedic surgeons and specialist registrars, regarding establishment of an Irish National Joint Register. The aim was to find out the possible reasons why a national joint register has not been established in Ireland. A 69% first response rate was recorded. Ninety-seven percent believe it is time to set up a registry and 81% say it should be made compulsory for unwilling surgeons and hospitals to participate. Despite the overwhelming support, privacy and liability issues were major concerns. Fifty-eight percent agree that access to registry report by general public can expose surgeons and hospitals to medico-legal implications. Legislation may be required to protect the integrity of a national joint replacement registry to ensure that the data are used as intended.


Subject(s)
Joint Diseases/surgery , Joints/surgery , Orthopedic Procedures/statistics & numerical data , Registries/statistics & numerical data , Databases as Topic , Humans , Ireland , Joint Diseases/pathology , Joints/pathology , Surveys and Questionnaires
18.
Article in English | MEDLINE | ID: mdl-23412144

ABSTRACT

As the age profile of our population expands, we can expect subsequent increase in patients presenting with intracapsular fracture. The onus remains on the surgeon to make all reasonable efforts to find new and innovative means of reducing associated morbidity and mortality of the treatment of these injuries. This challenge is particularly relevant in the elderly and in patients with multiple co-morbidities. In this study, 100 patients were randomly allocated into two groups. One group had dissection to the level of the hip joint under direct diathermy control; the other group had dissection using a scalpel with supplementary electrocautery. Intraoperative total blood loss prior to dissection of the abductors was measured by collecting blood using wound swabs using a local protocol and results were statistically analysed using PROC GLM SAS. We demonstrate a clear advantage in the use of diathermy to create a hip incision showing a significant reduction in wound-related blood loss and a reduction, whilst not statistically significant, in total operative blood loss using diathermy incision. Larger randomised prospective trials are necessary to study the effects of this intervention in a larger patient population so that these end-points can be adequately assessed.

19.
Bull Entomol Res ; 95(6): 621-34, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16336710

ABSTRACT

Populations of Homalodisca coagulata (Say) were sampled from citrus orchards in southern California, USA to characterize and quantify seasonal occurrences of nymphs and adults with the goal of identifying management opportunities through well-timed treatments and/or natural enemy releases. Higher densities of H. coagulata in 2001 contributed to a complete seasonal profile that began in early spring with the emergence of first instar nymphs and their progression through five nymphal instars lasting until mid-August. Adult emergence began in mid-June with peak adult densities attained from mid to late August followed by a gradual decline through autumn. A persistent and significant male bias was observed in the adult sex ratio from the time of first emergence through mid-October in oranges; the same trend was present in lemons, but with more variability. Adult densities gradually declined through the winter months into the following spring before rapidly increasing again in June as the 2002 spring generation of nymphs began emerging as adults. The seasonal timing of nymphs and adults in 2002 was nearly identical to that observed the previous year. Phenology data from both years were incorporated into a stochastic, temperature-dependent model that predicts the occurrences of H. coagulata stages through time. Applications of imidacloprid early in the spring generation of nymphs proved very effective at reducing nymphs and sustaining lower densities of adults through summer.


Subject(s)
Citrus/parasitology , Demography , Hemiptera , Animals , California , Imidazoles , Insect Control , Insecticides , Life Cycle Stages , Models, Biological , Neonicotinoids , Nitro Compounds , Seasons , Sex Ratio
20.
J Chem Ecol ; 31(10): 2289-308, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16195844

ABSTRACT

The glassy-winged sharpshooter (GWSS) is a xylem feeder that develops conspicuous, year-round populations in many citrus-producing regions of California. Field studies were conducted in a combined lemon and orange orchard to determine the influence of changing amino acid concentrations on relative densities of GWSS. Nineteen protein amino acids were detected in xylem fluid of both lemon and orange trees. Although annual profiles of total and essential amino acids were similar for each citrus species, mean concentrations were consistently higher in lemons than in oranges for most of the year, except for one critical period in late winter-early spring when concentrations were higher in oranges. Principal component analysis followed by factor analysis was performed individually on lemon and orange data sets to identify a reduced number of orthogonal factors composed of amino acids having similar seasonal profiles. Four factors were identified for each citrus species that accounted for 85% and 79% of the total variation in the orange and lemon analyses, respectively. These were then examined with respect to shifts in GWSS numbers that occurred asynchronously in lemons and oranges over the annual population cycle. Three distinctive number shifts were identified that included a peak in adult numbers in lemons during August 2001, significantly higher numbers in lemons relative to oranges during midwinter, and finally an increase in oranges of both adults and nymphs during spring 2002. Various groups of amino acids, i.e., factors, displayed peak annual or elevated levels during the intervals when shifts in GWSS numbers were occurring. Soluble protein levels in oranges and lemons did not correspond to shifting GWSS numbers as certain amino acids. However, soluble protein levels were higher in oranges during late winter/early spring when GWSS adults were sexually active. Potential roles of these amino acids and proteins in GWSS host selection are discussed.


Subject(s)
Citrus sinensis/metabolism , Citrus/metabolism , Hemiptera/physiology , Nitrogen/metabolism , Amino Acids/analysis , Amino Acids/chemistry , Animals , Citrus/growth & development , Citrus sinensis/growth & development , Fertilizers , Population Dynamics , Principal Component Analysis , Proteins/analysis , Proteins/chemistry , Seasons , Species Specificity
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