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Purpose of the study: The study aimed to develop and validate a holistically based follow-up pain assessment diary for patients with cancer pain in Sri Lanka. Design of the study: Mixed-method design adapted. Methods used: Developing a pain diary and testing its psychometric qualities were done in two phases. Comprehensive literature research and qualitative semistructured interviews with patients, clinical, and subject specialists created the pain diary items. Content, face, construct, criterion validity, and reliability were evaluated. Findings: The essential domains to be assessed were identified under six main categories; pain and related characteristics, physical, psychological, social, spiritual, and financial aspects. The average variance extracted from the subscales "Influence on daily life," "Gastric disturbances," and "Pain intensity" were 0.526, 0.562, and 0.696, respectively. The heterotrait-monotrait criterion values between subscales were from 0.691 to 0.44, which was lower than the threshold. Good to excellent correlation coefficients were demonstrated with the scores of reference tools. Cronbach's alpha was computed for each subscale and ranged from 0.75 to 0.92 and composite reliability from 0.921 to 0.826. Conclusions: Pain diary is a reliable and valid instrument for follow-up assessment of holistic pain experience enabling holistic nursing among patients with cancer pain in Sri Lanka.
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In this study, the ability of low-cost composite adsorbents to treat organic compounds in terms of chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) was investigated. The composite adsorbents were composed of washed sea sand (WSS), dewatered alum sludge (DAS), zero-valent iron (ZVI), and granular activated carbon (GAC). The removal efficiency of COD in landfill leachate by a composite adsorbent (composed of WSS (40%), DAS (40%), ZVI (10%), and GAC (10%) in weight) was 79.93 ± 1.95%. The corresponding adsorption capacity was 8.5 mg/g. During batch sorption experiments, the maximum COD removal efficiencies given by DAS, WSS, ZVI, and GAC were 16, 51.3, 42, and 100.0%, respectively. The maximum removal efficiencies of the above composite adsorbent for TN and TP were 84.9 and 97.4%, respectively, and the adsorption capacities were 1.85 and 0.55 mg/g, respectively. The Elovich isotherm model gave the best fit for COD, TN, and TP adsorption. This composite adsorbent can treat more than one contaminant simultaneously. The application of DAS and ZVI to make an efficient adsorbent for wastewater treatment would be a good re-use application for them, which would otherwise be landfilled directly after their generation.
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Poluentes Químicos da Água , Custos de Cuidados de Saúde , Nutrientes , Adsorção , Carvão Vegetal , Ferro , Nitrogênio , Fósforo , AreiaRESUMO
During the COVID-19 crisis, the apparel industry faced many challenges. Aggressive cost-cutting strategies became a top priority, and in turn, these influenced stressors and adversely affected business sustainability. This study examines the impact of aggressive strategies during the COVID-19 pandemic on business sustainability in the apparel industry of Sri Lanka. Further, it investigates whether the relationship between aggressive cost-cutting strategies and business sustainability was mediated by employee stress, considering aggressive cost reduction strategies and workplace environmental changes. This was a cross-sectional study with data collected from 384 employees in the apparel industry in Sri Lanka. Structural Equation Modelling (SEM) was applied to analyze the direct and indirect effects of aggressive cost reduction strategies and workplace environmental changes on sustainability with mediating effects of stress. Aggressive cost reduction strategies (Beta = 1.317, p = 0.000) and environmental changes (Beta = 0.251, p = 0.000) led to an increase in employee stress but did not affect business sustainability. Thus, employee stress (Beta = -0.028, p = 0.594) was not a mediator in the relationship between aggressive cost-cutting strategies and business sustainability; business sustainability was not a dependent variable. The findings proved that managing workplace stress, particularly improving stressful working environments and aggressive cost reduction strategies, can enhance employee satisfaction. Thus, managing employee stress could be beneficial for policymakers to focus on the area(s) required to retain competent employees. Moreover, aggressive strategies are unsuitable to apply during crisis to enhance business sustainability. The findings provide additional knowledge to the existing literature, enabling employees and employers to predict causes of stress and serve as a significant knowledge base for further studies.
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COVID-19 , Vestuário , Indústria Manufatureira , Pandemias , Humanos , COVID-19/epidemiologia , Estudos Transversais , Análise de Classes Latentes , Sri Lanka/epidemiologia , Indústria Manufatureira/métodos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Pest outbreaks, harmful algal blooms and population collapses are extreme events with critical consequences for ecosystems. Therefore, understanding the ecological mechanisms underlying these extreme events is crucial. We evaluated theoretical predictions on the size scaling and variance of extreme population abundance by combining (i) the generalized extreme value (GEV) theory and (ii) the resource-limited metabolic restriction hypothesis for population abundance. Using the phytoplankton data from the L4 station in the English Channel, we showed a negative size scaling of the expected value of maximal density, whose confidence interval included the predicted metabolic scaling (α = -1) supporting theoretical predictions. The role of resources and temperature in the distribution of the size-abundance pattern and residuals was well characterized by the GEV distribution. This comprehensive modelling framework will allow to elucidate community structure and fluctuations and provide unbiased return times estimates, thereby improving the prediction accuracy of the timing of the population outbreaks.
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Ecossistema , Fitoplâncton , Densidade Demográfica , Tamanho Corporal , TemperaturaRESUMO
AIMS: Associations between employment status and mental health are well recognised, but evidence is sparse on the relationship between paid employment and mental health in the years running up to statutory retirement ages using robust mental health measures. In addition, there has been no investigation into the stability over time in this relationship: an important consideration if survey findings are used to inform future policy. The aim of this study is to investigate the association between employment status and common mental disorder (CMD) in 50-64-year old residents in England and its stability over time, taking advantage of three national mental health surveys carried out over a 14-year period. METHODS: Data were analysed from the British National Surveys of Psychiatric Morbidity of 1993, 2000 and 2007. Paid employment status was the primary exposure of interest and CMD the primary outcome - both ascertained identically in all three surveys (CMD from the revised Clinical Interview Schedule). Multivariable logistic regression models were used. RESULTS: The prevalence of CMD was higher in people not in paid employment across all survey years; however, this association was only present for non-employment related to poor health as an outcome and was not apparent in those citing other reasons for non-employment. Odds ratios for the association between non-employment due to ill health and CMD were 3.05 in 1993, 3.56 in 2000, and 2.80 in 2007, after adjustment for age, gender, marital status, education, social class, housing tenure, financial difficulties, smoking status, recent physical health consultation and activities of daily living impairment. CONCLUSIONS: The prevalence of CMD was higher in people not in paid employment for health reasons, but was not associated with non-employment for other reasons. Associations had been relatively stable in strength from 1993 to 2007 in those three cross-sectional nationally representative samples.
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Serviços Comunitários de Saúde Mental/estatística & dados numéricos , Emprego/estatística & dados numéricos , Renda/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Estresse Psicológico/psicologia , Estudos Transversais , Emprego/psicologia , Inglaterra/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Transtornos Mentais/psicologia , Saúde Mental , Pessoa de Meia-Idade , Prevalência , Fatores Socioeconômicos , Estresse Psicológico/epidemiologiaRESUMO
In this work, the influence of induced losses on the saturable absorption by zinc nanoparticles photodeposited onto the core of an optical fiber end is reported. Samples with different losses were obtained by the photodeposition technique using a continuous wave laser at 1550 nm. The nonlinear absorption of the saturable absorber was characterized by the P-scan technique using a high-gain pulsed erbium-doped fiber amplifier. The results have demonstrated that for optical fibers with variable induced losses by deposited nanoparticles, the modulation depth increases proportionally based on the nonlinear absorption coefficient. With induced losses fixed at 3 dB, it was demonstrated that the modulation depth increased as a function of the optical power used in the photodeposition process. The saturation intensity of the saturable absorber presents small shifts for higher intensities.
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BACKGROUND: Plate developer is a chemical used in the printing industry and is a corrosive alkaline agent containing sodium metasilicate as the main substance. Plate developer poisoning is rare. Literature search revealed only a single case report of fatal sodium metasilicate poisoning (Z Rechtsmed 94(3):245-250, 1985). There are no reports of acute kidney injury related to ingestion of sodium metasilicate containing substances. CASE REPORT: A 52-year-old Sri Lankan male with a history of hypertension and affective disorder presented following ingestion of about 150 ml of plate developer solution. He developed severe upper airway obstruction due to laryngeal edema and underwent tracheostomy. While in the ward he developed features of acute kidney injury with high serum creatinine levels and persistent hyperkalemia which necessitated temporary haemodialysis. Because of the corrosive effect, he developed severe inflammation of the upper gastro intestinal tract with narrowing of esophagus and pyloric region, requiring feeding jejunostomy. He died while waiting for the surgery for pyloric stenosis. CONCLUSIONS: Acute kidney injury is a potential treatable complication of plate developer poisoning other than its complications related to corrosive effects. Regular monitoring of renal functions in such a patient would be useful for early recognition of acute kidney injury.
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Injúria Renal Aguda/etiologia , Ingestão de Alimentos , Silicatos/intoxicação , Evolução Fatal , Obstrução da Saída Gástrica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with increased risk of Parkinson's disease (PD). Thus, LRRK2 kinase inhibitors are in development as potential Parkinson's disease therapeutics. A reduction in the constitutive levels of phosphorylation on leucine-rich repeat kinase 2 (LRRK2) is currently used to measure target engagement of LRRK2 kinase inhibitors in cell and animal models. We aimed to determine if reduced phosphorylation of LRRK2 following inhibitor treatment is also a valid measure of target engagement in peripheral mononuclear cells from Parkinson's disease patients. Peripheral mononuclear cells from idiopathic Parkinson's disease patients and controls were treated ex vivo with two structurally distinct inhibitors of LRRK2, at four different doses, and immunoblotting was used to assess the reduction in LRRK2 phosphorylation at Ser910, Ser935, Ser955 and Ser973. Both inhibitors showed no acute toxicity in primary cells and both inhibitors reduced the constitutive phosphorylation of LRRK2 at all measured residues equally in both control and Parkinson's disease groups. Measuring the reduction in LRRK2 phosphorylation resulting from LRRK2 kinase inhibition, is thus a valid measure of acute peripheral target engagement in Parkinson's disease patients. This is important if LRRK2 kinase inhibitors are to be used in a clinical setting.
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Biomarcadores/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Leucócitos Mononucleares/citologia , Idoso , Linhagem Celular , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/antagonistas & inibidores , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson , Fosforilação , Proteólise , Serina/metabolismoRESUMO
The with no lysine (K) (WNK) family of enzymes is best known for control of blood pressure through regulation of the function and membrane localization of ion cotransporters. In mice, global as well as endothelial-specific WNK1 gene disruption results in embryonic lethality due to angiogenic and cardiovascular defects. WNK1(-/-) embryos can be rescued by endothelial-specific expression of a constitutively active form of the WNK1 substrate protein kinase OSR1 (oxidative stress responsive 1). Using human umbilical vein endothelial cells (HUVECs), we explored mechanisms underlying the requirement of WNK1-OSR1 signaling for vascular development. WNK1 is required for cord formation in HUVECs, but the actions of the two major WNK1 effectors, OSR1 and its close relative SPAK (STE20/SPS1-related proline-, alanine-rich kinase), are distinct. SPAK is important for endothelial cell proliferation, whereas OSR1 is required for HUVEC chemotaxis and invasion. We also identified the zinc-finger transcription factor Slug in WNK1-mediated control of endothelial functions. Our study identifies a separation of functions for the WNK1-activated protein kinases OSR1 and SPAK in mediating proliferation, invasion, and gene expression in endothelial cells and an unanticipated link between WNK1 and Slug that is important for angiogenesis.
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Células Endoteliais da Veia Umbilical Humana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Proliferação de Células/fisiologia , Regulação da Expressão Gênica/fisiologia , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Antígenos de Histocompatibilidade Menor , Neovascularização Fisiológica/fisiologia , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína Quinase 1 Deficiente de Lisina WNKRESUMO
INTRODUCTION: In 2009, the Royal New Zealand College of General Practitioners commissioned the development of a framework to facilitate quality-improvement activity in primary care settings. This paper outlines the development of the framework, which integrates concepts of quality with the reality of practice-based clinical care, and discusses its value for primary care quality improvement. METHOD: Framework development involved: (1) literature review of theoretical approaches to healthcare quality; (2) field work utilising a mixed methods approach to obtain empirical data; and (3) model design. RESULTS: Primary care practitioners are juggling competing priorities. Models and tools that promote quality-related activity at practice level need to take into account, and incorporate by design, day-to-day clinical and practice functions. CONCLUSIONS: The quality framework identifies the components of primary care practice and locates this model within the concepts and activities necessary for quality improvement. It may be used by primary care organisations and practices to facilitate focussed quality-improvement activity and self-directed process review. The framework was developed for, and within a New Zealand primary care setting, and is applicable internationally and within other healthcare settings.
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Padrões de Prática Médica , Atenção Primária à Saúde/organização & administração , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Pesquisas sobre Atenção à Saúde , Administradores de Instituições de Saúde , Humanos , Entrevistas como Assunto , Nova Zelândia , Atenção Primária à Saúde/normas , Garantia da Qualidade dos Cuidados de Saúde/métodosRESUMO
Dysfunction of mitochondria, the ubiquitin proteasome system (UPS), and lysosomes are believed to contribute to the pathogenesis of Parkinson's disease (PD). If it were possible to rescue functionally compromised, but still viable neurons early in the disease process, this would slow the rate of neurodegeneration. Here, we used a catecholaminergic neuroblastoma cell line (SH-SY5Y) as a model of susceptible neurons in PD. To identify a target early in the cell death process that was common to all neurodegenerative processes linked with PD, cells were exposed to toxins that mimic cell death mechanisms associated with PD. The sub-cellular abnormalities that occur shortly after toxin exposure were determined. 3 h of exposure to either naphthazarin, to inhibit lysosomal function, Z-Ile-Glu(OBu(t))-Ala-Leu-H (PSI), to inhibit the UPS, or rotenone, to inhibit mitochondrial complex I, caused depolarisation of the mitochondrial membrane potential (2.5-fold, twofold, and 4.6-fold change, respectively compared to vehicle), suggesting impaired mitochondrial function. Following 24 h exposure to the same toxins, UPS and lysosomal function were also impaired, and ubiquitin levels were increased. Thus, following exposure to toxins that mimic three important, but disparate cell death mechanisms associated with PD, catecholaminergic cells initially experience mitochondrial dysfunction, which is then followed by abnormalities in UPS and lysosomal function. Thus, mitochondrial dysfunction is an early event in cell stress. We suggest that, in patients with PD, the surviving cells of the substantia nigra pars compacta are most susceptible to mitochondrial impairment. Thus, targeting the mitochondria may be useful for slowing the progression of neurodegeneration in PD.
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Lisossomos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Ubiquitina/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Mitocôndrias/metabolismo , Naftoquinonas/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Rotenona/toxicidade , Fatores de TempoRESUMO
AIM/HYPOTHESIS: We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. METHODS: Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg(-1) day(-1), pump), or diabetic + lisinopril (10 mg kg(-1) day(-1), drinking water) rats were evaluated over 16 weeks. For oxygen-induced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg(-1) day(-1), pump) or lisinopril (10 mg kg(-1) day(-1), drinking water) was administered during retinopathy development between postnatal days 12 and 18. RESULTS: Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg(-1) day(-1) aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg(-1) day(-1) aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg(-1) day(-1) aliskiren and normalised by 30 mg kg(-1) day(-1) aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels. CONCLUSIONS/INTERPRETATION: Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.
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Amidas/uso terapêutico , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/tratamento farmacológico , Fumaratos/uso terapêutico , Oxigênio/toxicidade , Renina/metabolismo , Animais , Animais Geneticamente Modificados , Retinopatia Diabética/metabolismo , Feminino , Lisinopril/uso terapêutico , Camundongos , Neovascularização Patológica/tratamento farmacológico , Ratos , Renina/antagonistas & inibidores , Renina/genéticaRESUMO
Fondaparinux is an agent of choice for the prevention and initial treatment of venous thromboembolism (VTE) as well as myocardial infarction. Nevertheless, as a negatively charged molecule fondaparinux can pass the intestinal epithelial barrier after oral administration only partially. It was therefore the aim of this study to design a highly efficient small-intestinal-targeted oral delivery system for fondaparinux based on thiolated polycarbophil (PCP-Cys) and glutathione (GSH) combined with sodium decanoate. The formulations were tested in vitro with regard to their release, cytotoxicity profiles and their permeation-enhancing properties across small-intestinal mucosa. For the in vivo study, rats were treated with a single oral dose of fondaparinux gels or mini-tablets (5mg/kg) and the subcutaneous and intravenous groups with a dose of 200µg/kg fondaparinux. The anti-factor Xa activity in the plasma was measured. In the presence of PCP-Cys/GSH/sodium decanoate the uptake of fondaparinux from the intestinal mucosa was 4.1-fold improved. The area under concentration-time curve in rat plasma from 0 to 24h with PCP-Cys/GSH/sodium decanoate gel was 135.3µgmin/ml and 1.3-fold improved with the tablets. C(max) value of mini-tablets was 0.23µg/ml and the absolute bioavailability of 4.4% was 6.2-fold improved, while the control solution was not absorbed orally. PCP-Cys/GSH/sodium decanoate demonstrated potential for increasing the oral bioavailability of the indirect factor Xa inhibitor as an alternative to currently used subcutaneous delivery.
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Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacocinética , Administração Oral , Animais , Anticoagulantes/sangue , Disponibilidade Biológica , Células CACO-2 , Sobrevivência Celular , Fondaparinux , Géis , Humanos , Intestino Delgado , Masculino , Polissacarídeos/sangue , Ratos , Ratos Sprague-Dawley , Cremes, Espumas e Géis VaginaisRESUMO
This study was aimed at improving the mucoadhesive properties of carboxymethyl dextran by the covalent attachment of cysteine. Mediated by a carbodiimide, l-cysteine was covalently attached to the polymer. The resulting CMD-cysteine conjugate (CMD-(273) conjugate) displayed 273+/-20 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). Within 2h the viscosity of an aqueous mucus/CMD-(273) conjugate mixture pH 7.4 increased at 37 degrees C by more than 85% compared to a mucus/carboxymethyl dextran mixture indicating enlarged interactions between the mucus and the thiolated polymer. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (p<0.05). In aqueous solutions the CMD-(273) conjugate was capable of forming inter- and/or intramolecular disulfide bonds. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 15 min, whereas tablets of the CMD-(273) conjugate remained stable for 160 min (means+/-S.D.; n=3). Results from LDH and MTT assays on Caco-2 cells revealed 4.96+/-0.98% cytotoxicity and 94.1+/-0.9% cell viability for the CMD-(273) conjugate, respectively. Controlled release of model compound from CMD-(273) conjugate tablets was observed over 6h. These findings suggest that CMD-(273) conjugate is a promising novel polymer for drug delivery systems providing improved mucoadhesive and cohesive properties, greater stability and biocompatibility.
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Cisteína/química , Polímeros/química , Células CACO-2 , Carbodi-Imidas/química , Carbodi-Imidas/metabolismo , Cisteína/metabolismo , Dextranos , Sistemas de Liberação de Medicamentos/métodos , Humanos , Polímeros/metabolismo , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo , Comprimidos/metabolismo , Viscosidade , Água/metabolismoRESUMO
To analyse the Issuable Stock Index (days worth of stock) and wastage in relation to data continuously collected by the Blood Stocks Management Scheme (BSMS) with aspects of blood inventory management practice determined by the 2006 hospital inventory practice survey (IPS). The BSMS collects blood inventory data from hospitals and blood services in England, Wales and Northern Ireland. Data sets were constructed from information obtained from the 2006 IPS, which included questions on the crossmatch reservation period, methods for calculating the blood order and stock share relationships between hospitals. Two of the Scheme's measures that can indicate a hospital's blood inventory management performance were used to present blood stock and wastage data in a comparable format. Data were analysed using the Student's t-test. The results showed significantly lower inventory and wastage in hospitals which used a 24-h reservation period compared with 48 h (P = 0.02 and P = 0.04, respectively), and for hospitals that used their computer for calculating the blood order compared with those that used a 'visual review' (P = 0.02 and P < or = 0.001, respectively). A strong correlation co-efficient (0.61) was found for a relationship between a hospital's stock level and wastage. The study showed that differences in stock management practice between hospitals are associated with significant differences in stock levels and wastage of blood. The paper identifies examples of best practice.
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Armazenamento de Sangue/métodos , Inventários Hospitalares , Coleta de Dados , Eficiência Organizacional , Humanos , OrganizaçõesRESUMO
We report a case of regression of pulmonary and bony metastases in a patient with malignant melanoma following palliative treatment with systemic zoledronate and localised radiotherapy to the bone. Zoledronate is a potent new bisphosphonate used for the treatment of metabolic bone diseases including bone metastases due to its inhibitory effect on osteoclasts. In the context of metastatic cancer zoledronate is routinely used to improve bone pain and reduce the frequency of skeletal events. There is also an increasing body of evidence suggesting that bisphosphonates exhibit anti-tumour properties. Bisphosphonates are able to activate Vgamma9Vdelta2 gamma-delta T cells which can be key players in the immune defence against malignant cells. Furthermore bisphosphonates have direct anti-proliferative, anti-metastatic and pro-apoptotic effects on tumour cells. These actions, together with their low side effect profile, may prove to be useful therapeutic tools in the treatment of cancer even in the absence of bone metastases. On the basis of this case report we here review the current literature on present preclinical and clinical studies using bisphosphonates for the treatment of cancer.
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Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Apoptose , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Feminino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Melanoma/patologia , Melanoma/radioterapia , Pessoa de Meia-Idade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ácido ZoledrônicoRESUMO
Routine anatomical imaging with CT and MRI does not reliably indicate the true extent or the most malignant areas of gliomas and cannot identify the functionally critical parts of the brain. The aim of the study was to see if the use of MR spectroscopic imaging (MRSI) along with functional MRI (fMRI) can better define both the target and the critical structures to be avoided to improve radiation delivery in gliomas. 12 patients with gliomas underwent multivoxel MRS and functional imaging using GE processing software. The choline to creatine ratio (Cho:Cr), which represents the degree of abnormality for each individual voxel on MRSI, was derived, converted into a grayscale grading system, fused to the MRI images and then transferred to the planning CT images. An intensity-modulated radiation therapy (IMRT) plan was developed using the dose constraints based on both the anatomical and the functionally critical regions. Cho:Cr consistently identified the gross tumour volume (GTV) within the microscopic disease (clinical target volume, CTV) and allowed dose painting using IMRT. No correlation between MRSI based Cho:Cr > or =2 and MR defined CTV nor their location was noted. However, MRSI defined Cho:Cr > or =3 was smaller by 40% compared with post-contrast T1 weighted MRI defined GTV volumes. fMRI helped in optimizing the orientation of the beams. In conclusion, both MRSI and fMRI provide additional information to conventional imaging that may guide dose painting in treatment planning of gliomas. A Phase I IMRT dose intensification trial in gliomas using this information is planned.
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Neoplasias Encefálicas/patologia , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Encéfalo/patologia , Neoplasias Encefálicas/radioterapia , Colina/análise , Irradiação Craniana/efeitos adversos , Creatina/análise , Glioma/radioterapia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Under photoperiod regulated conditions, some Pelibuey ewes appear to express estrous cycles continuously throughout the year. Ovulatory activity of Suffolk ewes has not being determined at 19 degrees N. The aim of the present study was to describe the annual reproductive cycle of Pelibuey and Suffolk ewes under natural conditions at 19 degrees N. Ten adult ewes of each breed were maintained under natural environmental conditions, on a constant plane of nutrition and isolated from rams. The ovulatory activity of both breeds was monitored over 2 years (2003 and 2004) by quantifying progesterone concentrations in blood samples taken twice a week. For both breeds, the proportion of ovulating ewes per month and year was analyzed by chi(2). The duration of anestrus was compared between breeds and years by analysis of variance. Correlation of ambient temperature and weight changes with the ovulatory activity was evaluated by regression procedure. Ovulatory activity was different (P<0.05) between breeds from February to July. Pelibuey sheep (60%, 6 of 10) ovulated continuously during the entire study; one animal was eliminated in the second year, due to ovarian follicular cysts and three ewes had anestrous periods from 65+/-46 to 70+/-36 days. Suffolk ewes displayed reproductive seasonality similar to that observed in sheep of the same breed in latitudes greater than 35 degrees . Within breed, reproductive behavior of sheep was similar between years, with the only difference (P<0.05) observed in February for Pelibuey and in July for Suffolk relative to other months. Ambient temperature was not correlated with ovulatory activity. The body weight of Pelibuey ewes was constant during the entire study and was not correlated with ovulatory activity. There was, however, an increase on the body weight of Suffolk ewes, but this variation was not related to ovulatory activity. These findings lead to the conclusion that at 19 degrees N, a high proportion of Pelibuey ewes is capable of ovulating throughout the year, whereas Suffolk ewes undergo seasonal anestrous periods similar to those observed in individuals of the same breed at latitudes greater than 35 degrees . Identification of continuous ovulatory Pelibuey ewes may be the first step for developing a selection program against seasonality to increase lambing frequency.
Assuntos
Fotoperíodo , Reprodução/fisiologia , Reprodução/efeitos da radiação , Ovinos/fisiologia , Temperatura , Animais , Ciclo Estral/efeitos da radiação , Feminino , Luz , Ovulação/efeitos da radiação , Estações do Ano , Fatores de TempoRESUMO
OBJECTIVE: To assess the incidence of anti-tuberculosis (TB) drug induced hepatitis (AIH) in Sri Lankan patients, determine risk factors of AIH, and to address management options in AIH. DESIGN: A prospective study. SETTING: Chest Hospital, Welisara, Sri Lanka, from April 2001 to April 2002. PATIENTS: Seven hundred and eighty three patients with a confirmed diagnosis of TB and resident in the Colombo and Gampaha districts who presented to Chest Hospital, Welisara, Sri Lanka. METHODS: WHO recommended treatment was commenced in all cases. AIH was diagnosed when patients complained of decreased appetite with nausea or vomiting and elevated serum bilirubin (SB; >1.1 mg/dL) or elevated serum alanine transferase (ALT; > 3 times upper limit of normal). RESULTS: Of 783 enrolled patients, 74 (9.5%) developed AIH, the majority (58%) developing AIH within the first 2 weeks of the intensive phase of treatment. AIH was more common among patients over 60 years (p = 0.018), who developed pulmonary TB (p = 0.028), and in patients weighing 33-55 kg (p = 0.004). Age, weight and rifampicin overdosage were significant predictors of AIH. Of the 74 AIH patients, standard treatment was restarted in 60, treatment modified in six, two defaulted and six died. CONCLUSIONS: The incidence of AIH in Sri Lanka is 9.5% in treated patients. AIH was associated with age, low body weight and rifampicin overdosage.