RESUMO
INTRODUCTION: Factor XI (FXI) deficiency is the commonest of the rare bleeding disorders, affecting 2079 individuals in the United Kingdom. Treatment options for bleeding or surgery include antifibrinolytics, fresh frozen plasma or plasma-derived (pd) FXI concentrates. There were a number of reports of thrombosis following treatment with FXI concentrates prior to changes in their manufacturing processes made in the mid-1990's. AIMS: The aim of the study was to determine the occurrence of adverse events (haemorrhagic and thrombotic) following usage of pd-FXI concentrates at two large UK haemophilia centres. Retrospective chart review of all consecutively treated patients with BPL Factor XI(®) or Hemoleven(®) over a 5-year period (11/06-11/11) was performed. RESULTS: Twenty-nine patients (median age = 57.1 years) received treatment over 64 treatment episodes (surgery = 56, bleeding = 5, other = 3), using 126 000 U of concentrate. Median baseline FXI:C was 9 U dL(-1) (range = <1-51), with 21 having severe and eight partial deficiency. BPL Factor XI(®) was used in 39 episodes (79 110 U) and Hemoleven(®) 25 episodes (46 890 U). There were six clinically significant bleeding events, managed either with a single additional dose of FXI concentrate (n = 4) or requiring no further intervention (n = 2). One patient required blood transfusion and one oral iron replacement. Two thrombotic events (transient ischaemic attack and pulmonary emboli), occurred in two patients with severe FXI deficiency, despite cautious FXI concentrate usage in the perioperative period. CONCLUSIONS: FXI concentrate use is efficacious and safe in the majority of cases although physicians should remain mindful of the possibility of thrombotic complications.
Assuntos
Deficiência do Fator XI/tratamento farmacológico , Fator XI/uso terapêutico , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Cálculos da Dosagem de Medicamento , Fator XI/efeitos adversos , Deficiência do Fator XI/patologia , Feminino , Hemostasia Cirúrgica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Adulto JovemRESUMO
Children with von Willebrand disease (VWD) in whom DDAVP is ineffective or contraindicated require treatment with a coagulation factor concentrate containing von Willebrand factor (VWF) and factor VIII (FVIII). The aim of this study was to monitor the safety, efficacy and tolerability of Wilate(®) (a VWF:FVIII concentrate with a 1:1 ratio) used across the North London Paediatric Haemophilia Network since May 2010. In total, 47 children (aged 0.0-17.0 years) with type 1 (n = 28), type 2 (n = 7), type 3 (n = 10) and acquired VWS (n = 2) have been treated for bleeds, surgery and/or prophylaxis using 260 000 IU Wilate(®). Analysis of dose and frequency of treatment show expected responses to treatment with mean doses of 55, 50 and 50 IU kg(-1) for bleeds, surgery and prophylaxis respectively. Most bleeds responded to a single treatment. Surgical procedures were covered with clinician approved dosing schedules with 95% (39/41) reported as having excellent or good efficacy. There was no accumulation of FVIII or VWF and no thromboembolic events. This case series confirms the efficacy, safety and tolerability of Wilate(®) in neonates, children and adolescents when used on-demand, prophylactically and in the surgical setting.
Assuntos
Fator VIII/farmacologia , Hospitais Universitários/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/farmacologia , Adolescente , Criança , Pré-Escolar , Técnicas de Laboratório Clínico , Combinação de Medicamentos , Fator VIII/uso terapêutico , Feminino , Hemorragia/complicações , Hemostasia/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Londres , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos , Doenças de von Willebrand/complicações , Doenças de von Willebrand/fisiopatologia , Doenças de von Willebrand/cirurgia , Fator de von Willebrand/uso terapêuticoRESUMO
von Willebrand disease (VWD) is the commonest inherited bleeding disorder. Management of major surgery or bleeding often requires treatment with a plasma-derived (pd) VWF/FVIII containing concentrate. Wilate® is a dual-virally inactivated pd-concentrate, produced specifically for the treatment of VWD, containing physiological (1:1) ratios of VWF: FVIII. We reviewed efficacy and safety of Wilate® usage (2007-2012) at our centre including 2 years following product switching the majority of patients. Clinical and laboratory data of all adult patients treated with Wilate® during the study period were evaluated. Fifty four patients used 3 972 150 IU of Wilate® (1378 infusions) between 1/3/07 and 1/5/12. Efficacy was rated as being excellent or good in 94% of surgical episodes (n = 70; 34 patients) and 98% of bleeding/traumatic episodes (n = 46; 25 patients). Eight patients (2 636 100 IU) were managed on home treatment regimens. Two patients switched to Wilate® prophylaxis in the evaluation period, demonstrating similar efficacy to a previous product. Incremental recoveries (n = 37) were 2.24 IU dL(-1) per IU kg(-1) for FVIII:C, 2.39 IU dL(-1) per IU kg(-1) for VWF:Ag and 1.88 IU dL(-1) per IU kg(-1) for VWF:RCo. Six adverse events occurred in six patients (11.1% patients) over 1378 infusions (0.44%). Half of these were retrospectively felt to be infusion speed related. No notable accumulation of FVIII was seen in patients treated for ≥3 days. There was no treatment failure, thrombosis, transfusion transmitted infection or inhibitory VWF antibodies seen. Our findings confirm safety and efficacy of Wilate® in an adult VWD population with lack of notable FVIII accumulation.
Assuntos
Fator VIII/uso terapêutico , Doenças de von Willebrand/tratamento farmacológico , Fator de von Willebrand/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Fator VIII/administração & dosagem , Fator VIII/efeitos adversos , Feminino , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Medicação , Estudos Retrospectivos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Resultado do Tratamento , Ferimentos e Lesões/complicações , Adulto Jovem , Doenças de von Willebrand/complicações , Doenças de von Willebrand/diagnóstico , Fator de von Willebrand/administração & dosagem , Fator de von Willebrand/efeitos adversosRESUMO
Titanium layers are used to promote adhesion between polymer substrates for flexible electronics and the Cu or Au conducting lines. Good adhesion of conducting lines in flexible circuits is critical in improving circuit performance and increasingcircuit lifetime. Nominally 50 nm thick Ti films on polyimide (PI) are investigated by fragmentation testing under uniaxial tensile load in the as-deposited state, at 350 °C, and after annealing. The cracking and buckling of the films show clear differences between the as-deposited and the thermally treated samples, cracks are much straighter and buckles are smaller following heat treatment. These changes are correlated to a drop in adhesion of the samples following heat treatment. Adhesion values are determined from the buckle dimensions using a total energy approach as described in the work of Cordill et al. (Acta Mater. 2010). Cross-sectional transmission electron microscopy of the Ti/PI interface found evidence of a ~ 5 nm thick interlayer between the largely columnar Ti and the amorphous PI. This interlayer is amorphous in the as-deposited state but nano-crystalline in those coatings tested at elevated temperature or annealed. It is put forward that this alteration of the interfacial structure causes the reduced adhesion.
RESUMO
The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.
Assuntos
Genes/genética , Camundongos/genética , Animais , Biologia Computacional , Bases de Dados Factuais , Etiquetas de Sequências Expressas , Biblioteca Gênica , Genoma , Análise de Sequência de DNA/estatística & dados numéricosRESUMO
Patients with inherited bleeding disorders (IBD) can face difficulty in accessing primary dental care either due to disease-specific or patient-related barriers. This can lead to poor oral health and increase the need for more invasive dental treatment. This study aimed to highlight actual and perceived barriers that IBD patients from the East London area were experiencing. It also gives an overview of the experience history of the General Dental Practitioners (GDPs) treating these patients. Information was gathered via pre-designed surveys as part of a service development audit. A total of 105 anonymous patient surveys and 50 GDP surveys were completed between December 2010 and July 2011. The patient survey highlighted more patients to be affected by patient-related than disease-specific barriers to access dental care. The GDP survey identified that just under half of GDPs questioned were not confident in the dental management of patients with bleeding disorders. Identifying misconceptions and barriers to access primary dental care will enable further development of our shared-care approach between General Dental Services, Hospital or Community Dental Services and Haemophilia Centre, optimizing regular preventative advice and follow ups to prevent dental disease and invasive dental treatment requiring haemostatic treatment.
Assuntos
Transtornos Herdados da Coagulação Sanguínea , Assistência Odontológica para Doentes Crônicos/normas , Serviços de Saúde Bucal/normas , Acessibilidade aos Serviços de Saúde/normas , Atitude do Pessoal de Saúde , Competência Clínica , Humanos , Londres , Guias de Prática Clínica como Assunto , Inquéritos e QuestionáriosRESUMO
Several studies of loss of constitutional genetic heterozygosity in the development of hepatocellular carcinoma have been carried out with the aim of determining the location of relevant tumour suppressor genes, but there is as yet no report of a similar investigation in hepatocellular adenomas. In this study we analyzed six such patients searching for evidence of chromosome allele loss, or loss of heterozygosity, with 25 DNA probes recognising restriction fragment length polymorphisms. The 25 probes have been assigned to 21 chromosome arms. None of those probes detected allele loss in any of the 6 tumours. One of the patients had a synchronous hepatocellular carcinoma. Chromosome 17p allele loss was detected in her hepatocellular carcinoma but not in the adenoma. The study suggests that chromosome allele loss is not a frequent genetic change in the development of hepatocellular adenoma.
RESUMO
A major advance in the understanding of the control of appetite, food intake, and energy expenditure came with the discovery of leptin. Leptin concentrations correlate with adipose tissue mass, and leptin acts via the central nervous system (CNS) to reduce food intake and increase energy expenditure. A variety of different neurotransmitters have been implicated in mediating the CNS effects of leptin. In humans, leptin deficiency is unlikely to be a major cause of obesity. Most humans are not leptin deficient, but have a leptin concentration raised in proportion to their fat mass. A recent clinical trial looking at the use of recombinant leptin in treating human obesity has resulted in only variable amounts of weight loss. The role of leptin extends beyond the control of food intake and energy expenditure. Leptin reverses many of the physiological responses to starvation. It is suggested that the main role of leptin might be in response to food deprivation and not in obesity.
Assuntos
Leptina/fisiologia , Obesidade/tratamento farmacológico , Receptores de Superfície Celular , Animais , Proteínas de Transporte/metabolismo , Humanos , Leptina/uso terapêutico , Camundongos , Receptores para Leptina , Proteínas Recombinantes/uso terapêutico , InaniçãoRESUMO
In 1998, the authors, acting on behalf of the National Board of Medical Examiners (NBME), undertook a review of the scoring policy for the United States Medical Licensing Examination (USMLE). The main goal was to determine the likely effect of changing from numeric score reporting to reporting pass-fail status. Several groups were surveyed across the nation to learn how they felt they would be affected by such a change, and why: all 54 medical boards; 1,600 randomly selected examinees (including 250 foreign medical graduates) who had recently taken either Step 1, Step 2, or Step 3 of the USMLE; 2,000 residency directors; the deans, education deans, and student affairs deans at all 125 U.S. medical schools accredited by the Liaison Committee on Medical Education; and all 17 members of the Council of Medical Specialty Societies. Responses from the different groups surveyed varied from 80% to a little less than half. The authors describe in detail the various views of the respondents and their reasons. Some members in each group favored each of the reporting formats, but the trend was to favor numeric score reporting. The majority of the responding examinees desired that their USMLE scores be sent to them in numeric form but sent to their schools and to residency directors in pass-fail form. Based on the responses and a thorough discussion of their implications, the Composite Committee (which determines USMLE score-reporting policy) decided that there is no basis at this time for changing the current policy, but that it would review the policy in the future when necessary.
Assuntos
Competência Clínica/estatística & dados numéricos , Avaliação Educacional , Licenciamento , Coleta de Dados , Estados UnidosRESUMO
BACKGROUND: Human telomerase reverse transcriptase (hTERT) has been identified as the catalytic subunit of telomerase ribonucleoprotein complex known to be required for cellular immortality and oncogenesis. Although human telomerase activity (hTA) is considered as a general marker for malignancy based on its presence in most malignant tumors including bladder cancer, its detection in urine is affected by many factors. The objective of this study was to compare the clinical utility of detecting urine hTERT messenger RNA (mRNA) by multiplex hTERT/GAPDH RT-PCR and urine hTA by telomerase repeat amplification protocol (TRAP) in the diagnosis of bladder cancer. METHODS AND RESULTS: Cystoscopy urine samples or bladder washes prospectively collected from 35 patients with confirmed (35) or clinically suspected (5) transitional cell carcinoma (TCC) of the bladder were examined by TRAP, hTERT/GAPDH RT-PCR, and urine cytology. The control group comprised 21 healthy volunteers and 3 patients without TCC. The hTERT/GAPDH RT-PCR test showed significantly higher diagnostic sensitivity than TRAP assay (94.3% vs 48.6%, P <.001) and urine cytology (95.2% vs 61.9%, P =.008) for confirmed TCCs. In particular, for superficial TCCs low grade (I-II), the hTERT/GAPDH RT-PCR test outperformed TRAP (90% vs 25%, P <.001) and urine cytology (91.7% vs 58.3%, P =.46). The overall specificity of the hTERT/GAPDH RT-PCR, TRAP and urine cytology was 92% (22/24), 100% (24/24), and 100% (3/3), respectively. A positive hTERT mRNA expression was also detected in urologic specimens from 3 patients with previous history of TCC, 3 to 6 months before cystoscopic evidence of cancer. CONCLUSION: In this pilot study, the hTERT mRNA expression in urine sediments is a more sensitive marker for diagnosis of TCC of the bladder than hTA and cytology. However, there is a higher false-positive rate.
Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/enzimologia , RNA Mensageiro , RNA , Telomerase/urina , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/urina , Domínio Catalítico/genética , Proteínas de Ligação a DNA , Ativação Enzimática/genética , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , RNA Mensageiro/urina , RNA Neoplásico/urina , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Bexiga Urinária/urina , Urina/citologiaRESUMO
Zinc sulfide clusters were synthesized and characterized at low micromolar concentrations to assess the effect of metal-sulfide ligands on metal toxicity to aquatic organisms in oxic environments. Recommended preparation times are greater than 2 h initial reaction of equimolar sodium sulfide and zinc nitrate, followed by oxic aeration for 3 d. Ionic strength, pH, and anoxic stabilization time were found to be relatively unimportant in controlling the final yield. Adsorptive losses of zinc sulfide (ZnS) clusters to surfaces, however, were significant for a variety of vessel materials and membrane filters. Ionic strength and pH were found to be important factors controlling the extent of adsorptive losses with minimal loss for pHs greater than 9 and for soft waters. The Ag(I), Cu(II), and Hg(II) as metal sulfides completely suppress the analysis of sulfide, whereas Pb(II), Mn(II), and Co(II) partially suppress the analysis of sulfide by the methylene blue technique. Ultraviolet and fluorescence spectra are shown for synthesized ZnS clusters.
Assuntos
Sulfetos/química , Sulfetos/síntese química , Poluentes da Água/toxicidade , Compostos de Zinco/química , Compostos de Zinco/síntese química , Adsorção , Concentração de Íons de Hidrogênio , Ligantes , Espectrometria de Fluorescência , Sulfetos/toxicidade , Testes de Toxicidade , Raios Ultravioleta , Compostos de Zinco/toxicidadeRESUMO
The case of a newborn infant with the Kassabach-merritt syndrome who presented with a significant intrauterine ocular and skin hemorrhage, followed shortly after birth by a massive hematemesis, is reported. The presence of cavernous hemangioma at birth should be a reminder of the risk of major hemorrhagic complications due to thrombocytopenia secondary to platelet trapping.
Assuntos
Hemangioma Cavernoso/complicações , Hematemese/etiologia , Hemorragia/etiologia , Doenças do Recém-Nascido/patologia , Oftalmopatias/etiologia , Feminino , Hemangioma Cavernoso/patologia , Humanos , Recém-Nascido , Dermatopatias/etiologia , Síndrome , Trombocitopenia/etiologiaRESUMO
Although there are successful examples of interdisciplinary education this generally relates to pre-registration health-care professionals. Post-registration projects are usually confined to skills workshops or social science subjects, which rarely include medical staff. This project was unusual in its attempt to combine the needs of experienced practitioners with those of medical students. There are practical issues for this form of learning such as, the organization of modules into 'systems' when health-care professionals (as part of a parallel project) indicated their interests lay in courses that related to clinical practice organized around disease processes/conditions. This case study demonstrates that concerns related to the potential mismatch of clinical expertise, maturity and scientific background are not insurmountable problems, and that clear benefits can be gained. It could be argued that until pre- and post-graduate medical staff are integrated with other disciplines, the real benefits of shared understanding, enhanced team work and mutual respect will remain illusive. It is not anticipated that this form of learning would be suitable for the majority of practitioners, whose core needs are generally met by existing opportunities. However, there is a need for a greater depth of academic understanding particularly for those in senior positions or in specific specialized areas (also identified in the parallel study) and for those whose roles are expanding. These practitioners are more likely to have the ability to apply their new knowledge to clinical practice, using reflective techniques with minimal facilitation to enhance their established clinical expertise. For them this model of learning offers the opportunity to tailor education to the individual needs of the practitioner without the costly establishment of complete new programmes of learning. This case study proved particularly successful for the participants as they enhanced understanding and confidence in the knowledge underpinning their practice. This enabled them to better anticipate patients needs, to identify complications and initiate action at an earlier stage. Their appreciation of rationale underpinning medical treatment has enabled them to support junior medical staff, and to promote the continuity of appropriate care. They are more active in the education of patients, relatives and staff, and have identified specific developments which will be informed by the knowledge they have gained. It also proved beneficial to junior medical staff with whom interdisciplinary working has improved. Each organization involved in facilitating the initiative also benefited by gaining mutual understanding and appreciation of systems, constraints and opportunities. Equally, relationships among them have been strengthened and key issues with practical solutions have been identified to inform future joint ventures. Indications suggest that there would be value in using this case study to inform a structured pilot project involving other modules of learning and potentially other disciplines. If successful it could benefit all health-care professionals, particularly those senior staff who are expanding their roles and have educational needs unmet by existing provision. In addition to providing complementary opportunities this format provides a mechanism to enhance the mutual understanding essential to effective teamwork.
Assuntos
Educação de Graduação em Medicina/organização & administração , Educação Continuada em Enfermagem/organização & administração , Recursos Humanos de Enfermagem Hospitalar/educação , Equipe de Assistência ao Paciente/organização & administração , Estudantes de Medicina , Gastroenterologia/educação , Humanos , Pesquisa em Educação em Enfermagem , Avaliação de Programas e Projetos de SaúdeRESUMO
Much has been written on the education of patients about their medication, and yet what patients need to know has not been identified and agreed upon by professionals. This study sought to design a tool for this purpose using a series of interviews with experts to identify categories of information. Many core categories were identified and ambiguous sections such as 'side-effects' were clarified. A test-re-test strategy was used to identify the reliability of the resulting questionnaire. A high level of inconsistencies and a low response rate were, in part, attributable to poor design and distribution of the questionnaire. Other contributory factors and the reluctance/inability of respondents to identify what they felt patients should know about their medication are discussed. Some deficits are identified, in addition to an agreement that current systems for educating patients are inadequate. Areas for future research are also identified.
Assuntos
Tratamento Farmacológico/enfermagem , Necessidades e Demandas de Serviços de Saúde , Avaliação em Enfermagem , Educação de Pacientes como Assunto/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Patients and relatives often assume nurses have a higher level of knowledge than they actually possess. In the search for a professional body of knowledge, nurses may underestimate the valuable lessons patients can teach them. The nursing press may exacerbate the theory-practice gap by underrepresenting the experiences of patients, careers and relatives.