eMelanoBase: An online locus-specific variant database for familial melanoma

A proportion of melanoma,prone individuals in both familial and non,familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1a, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A,p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model,view. controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.e, du.au:8080/melanoma.html.

Clinicians' attitudes to clinical practice guidelines

To the Editor: In their systematic review of clinicians' attitudes to clinical practice guidelines, Farquhar et al1 found that, although healthcare providers reported high satisfaction with guidelines, a significant number also expressed concerns about their practicality, their role in cost-cutting and their potential for increasing litigation. The review, however, did not address other potentially significant concerns of clinicians regarding the perceived validity of guidelines and the influence of external agencies (such as the pharmaceutical industry) on treatment recommendations.

Clinical and economic impact of exercise electrocardiography and exercise echocardiography in clinical practice

Background Patients with known or suspected coronary disease are often investigated to facilitate risk assessment. We sought to examine the cost-effectiveness of strategies based on exercise echocardiography and exercise electrocardiography. Methods and results We studied 7656 patients undergoing exercise testing; of whom half underwent exercise echocardiography. Risk was defined with the Duke treadmill score for those undergoing exercise electrocardiography alone, and by the extent of ischaemia by exercise echocardiography. Cox proportional hazards models, risk adjusted for pretest likelihood of coronary artery disease, were used to estimate time to cardiac death or myocardial infarction. Costs (including diagnostic and revascularisation procedures, hospitalisations, and events) were calculated, inflation-corrected to year 2000 using Medicare trust fund rates and discounted at a rate of 5%. A decision model was employed to assess the marginal cost effectiveness (cost/life year saved) of exercise echo compared with exercise electrocardiography. Exercise echocardiography identified more patients as low-risk (51% vs 24%, p<0.001), and fewer as intermediate- (27% vs 51%, p<0.001) and high-risk (22% vs 4%); survival was greater in low- and intermediate- risk and less in high-risk patients. Although initial procedural costs and revascularisation costs (in intermediate- high risk patients) were greater, exercise echocardiography was associated with a greater incremental life expectancy (0.2 years) and a lower use of additional diagnostic procedures when compared with exercise electrocardiography (especially in lower risk patients). Using decision analysis, exercise echocardiography (Euro 2615/life year saved) was more cost effective than exercise electrocardiography. Conclusion Exercise echocardiography may enhance cost-effectiveness for the detection and management of at risk patients with known or suspected coronary disease. (C) 2003 Published by Elsevier Science Ltd on behalf of The European Society of Cardiology.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

Site-directed mutagenesis of the ATM promoter: Consequences for response to proliferation and ionizing radiation

Although ATM, the protein defective in ataxia-telangiectasia (A-T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700-bp sequence reveals a number of potentially important cis-regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation-induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, gammaIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [gammaIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8-fold in these and other cell lines. Radiation activated the promoter approximately 2.5-fold in serum-starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A-T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co-immunoprecipitation could explain the altered regulation of Sp1 in A-T cells. The data described here provide additional evidence that basal and radiation-induced regulation of the ATM promoter is under multifactorial control. (C) 2003 Wiley-Liss, Inc.

Testamentary capacity and aphasia: A descriptive case report with implications for clinical practice

Background: Testamentary capacity (the capacity to make a will) is recognised in the literature as an important issue for speech-language pathologists' assessment of people with aphasia, but current guidelines for clinical practice lack an empirical base. Aims: The research aimed to suggest some guidelines for clinical practice based on information considered relevant for the court in determining testamentary capacity. Methods & Procedures: A recent legal case involving a challenge to the will of a woman with severe aphasia was critically examined with reference to current guidelines in the literature regarding assessment of testamentary capacity. Outcomes & Results: Examination of the information available on the case indicated that the judge gave priority to accounts of the everyday communication of the person with aphasia (including reported discourse samples) over the information provided by expert medical witnesses. The extent to which communication effectiveness could be maximised was found to be a matter of key significance to the determination of capacity. Conclusions: This study has implications for speech-language pathologists' assessment practices and reports, as well as for scope of practice with regard to legal decision making of people with aphasia. These issues are discussed in relation to the World Health Organisation's ICF framework of functioning for social participation.

Inverted canines in the Staffordshire Bull Terrier - a new clinical condition

A condition is described where the mandibular canine teeth of Staffordshire Bull Terriers are tipped (curved) caudally and impact at the mesio-palatal gingival margin of the maxillary canine teeth. The aetiology of the condition and possible treatment options are discussed.

Effect of central venous catheter type on infections: a prospective clinical trial

This study reports on a block clinical trial of two types of central venous catheters (CVCs): antiseptic-impregnated catheters (AIC) and non-impregnated catheters (non-AIC), on catheter tip colonization and bacteraemia. In total, 500 catheters were inserted in 390 patients over the 18 month study period, 260 (52.0%) AIC and 240 (48.0%) non-AIC. Of these, 460 (92.0%) tips (237 AIC and 223 non-AIC) were collected. While significantly fewer AIC, 14 (5.9%), than non-AIC, 30 (13.5%), catheters were colonized (P < 0.01), there was no difference in the rates of bacteraemias in the two groups (0.8% vs. 2.7%, respectively, P = 0.16). There were 6.87 (95% CI 3.38-14.26) and 16.92 (95% CI 10.61-27.12) colonized AIC and non-AIC catheters, respectively, per 1000 catheter days, a difference that was significant (P < 0.01). However, no difference emerged between bacteraemias in AIC and non-AIC catheters per 1000 catheter days measured at 0.98 (95% CI 0.24-5.54) and 3.38 (95% CI 1.29-9.34), respectively (P = 0.10). Of the 444 CVCs that were sited in the subclavian or jugular veins and had tips collected, significantly more catheters were colonized in the jugular group, 19 (20%), compared with the subclavian group, 24 (6.9%; P less than or equal to 0.01). Overall, the low rates of colonization and bacteraemia may be explained by the population studied, the policies used and the employment of a clinical nurse dedicated to CVC management. (C) 2003 The Hospital Infection Society. Published by Elsevier Science Ltd. All rights reserved.

Clinical aspects of gestational trophoblastic disease: A review based partly on 25-year experience of a statewide registry

Background: Gestational trophoblastic disease is a fascinating group of pregnancy disorders characterised by abnormal proliferation of trophoblast, ranging from benign to malignant. Because the disease is uncommon, there is a need to formulate management with the assistance of collective information. Methodology: A review of available information from English written literature was undertaken especially data reported by registries around the world (Charing Cross Hospital in England, the North-western University and the New England area in the USA as well as our own experience in Queensland, Australia). Where possible, collated data from relevant studies were analysed to answer some of the questions posed in clinical practice, with reference to metastatic disease to liver and brain, twinning of molar gestation and coexisting fetus, and placental-site tumour. Results: We found that molar gestation can be classified according to its clinical presentation which influences the time taken to reach human chorionic gonadotropin (HCG) 'negativity' and the risk of persisting disease. Categorisation of risk is the basis for choice of chemotherapy to achieve good outcomes. Metastases to liver and brain remain problems in management; the development of 'new' metastases during chemotherapy is a very poor prognostic factor. In the variant of twinning with molar gestation and coexisting fetus, it is important to elucidate the fetal karyotype in planning management: a 69XXX fetus is not salvageable but a normal 46XX or 46XY fetus faces the prospect of early preterm delivery. The placental-site tumour is very rare; localised disease is curable by surgery; chemotherapy is less effective in disseminated disease. From collated worldwide data, the recurrence rate after one mole is 1.3% and after two or more is 20%. Reproductive outcome in subsequent pregnancies, even after multidrug chemotherapy, is not different from the general population. Because of the increased risk long-term of second tumours after multidrug chemotherapy a closer surveillance of these patients is necessary Conclusion: In general, the disease in its persisting or malignant form is 'a cancer model par excellence' because of an identifiable precursor condition, a reliable HCG marker, and sensitivity of the disease to cytotoxic drugs. With current management, retention of fertility is possible and normal reproductive outcome assured.

Moralidade e plágio : um estudo com alunos do ensino médio

Nosso objetivo foi compreender o juízo da representação da ação de plágio de estudantes do segundo e terceiro anos do ensino médio, provenientes de escolas públicas e particulares de Vitória, Espírito Santo. Participaram 40 discentes entre 16 a 18 anos, que frequentavam três escolas públicas e duas privadas da cidade de Vitória-ES, divididos igualmente quanto a sexo e tipo de instituição. Nosso instrumento de pesquisa foi a um roteiro de entrevista semiestruturado, contendo uma história-fictícia que envolveu o comportamento de plágio. As entrevistas foram realizadas individualmente, em consonância com o método clínico piagetiano e, como procedimento de análise dos protocolos, utilizamos a sistematização de categorias proposta por Delval. Avaliamos os juízos dos adolescentes com relação a representação da ação de plágio do personagem da história-fictícia contada, nos seguintes aspectos: se consideravam a ação certa ou errada, se o plagiário deve ou não ser punido e qual (is) a (s) penalidade (s) sugerida (s). Foram solicitadas as justificativas de todos os aspectos anteriormente mencionados. A partir dos dados encontrados, constatamos que a maior parte dos estudantes: 1) considerou que o plágio é uma atitude errada; 2) justificou ser errado, principalmente pela “negligência do aluno no cumprimento do trabalho”, pela “possibilidade de consequência negativa” e pela “ação ser incorreta”; 3) afirmou que o personagem “deve ser punido”; 4) analisou, como castigo para este ato, “fazer um novo trabalho”, uma “conversa” e “receber nota zero no trabalho” plagiado e, por fim, 5) justificou as sanções sugeridas em virtude da “oportunidade de aprendizado e/ou reflexão do aluno com a punição” da “adequabilidade da punição” e da “possibilidade de consequência negativa para o aluno”. Por outro lado, as razões dos poucos escolares que consideravam que o personagem da história “não deve ser penalizado” foram a favor da “ausência de especificação e/ou proibição pelo docente” e por causa do plágio ser um “fato rotineiro”. De maneira geral, os dados de nossa pesquisa mostram que os participantes sabem que é errado plagiar, reconhecem que não se deve fazer este ato e a maioria dos estudantes penalizou a conduta investigada. Esse trabalho pode contribuir para a ampliação dos estudos na área da moralidade e colaborar com subsídios teóricos para a elaboração de projetos de educação em valores morais que contemplem, de uma forma geral, o enfrentamento da desonestidade acadêmica e, especificamente, o plágio. Consideramos que a inserção desse conteúdo nas propostas de educação em valores morais contemporâneas poderá enriquecer a formação moral dos estudantes. Assim, esperamos, a partir dos resultados encontrados na presente pesquisa, subsidiar e promover a realização de outros estudos e propiciar discussões e ações sobre o referido tema, principalmente na Psicologia e na Educação.

Prevalência de Chlamydia trachomatis em casos de partos pretermo atendidos no Hospital Universitário Cassiano Antonio Moraes, Vitória - ES

Introdução: O parto pretermo (PPT) é um dos principais determinantes da morbimortalidade neonatal, acarretando consequências adversas para saúde. As causas são multifatoriais, sendo a infecção intrauterina a razão mais provável para explicar a maioria destes desfechos. Acredita-se que a infecção por Chlamydia trachomatis (CT) também esteja envolvida no PPT e rotura prematura de membranas (ROPREMA). Objetivo: Determinar a prevalência de CT em parturientes e os possíveis fatores de risco relacionados com os casos de partos prematuros atendidos no Hospital Universitário Cassiano Antonio Moraes. Métodos: Estudo de corte transversal, realizado entre parturientes que apresentaram PPT em um Hospital Universitário em Vitória - ES, entre junho de 2012 e agosto de 2013. As participantes responderam a um questionário contendo dados sóciodemográficos, comportamentais e clínicos. Foi coletada uma amostra de urina para rastreio de CT usando reação em cadeia da polimerase. Resultados: A prevalência de PPT durante o período do estudo foi de 26%. Um total de 378 casos de PPT foram registrados, entre eles 323 mulheres foram testadas para o CT; quarenta e cinco (13,9%) tiveram um resultado positivo, sendo que 31,6% possuiam até 24 anos e as mulheres infectadas pela CT eram mais jovens do que as demais (p = 0,022). Um total de 76,2% eram casadas/em união estável, e CT foi mais frequente entre as solteiras (p = 0,018); 16,7% relataram primeira relação sexual com menos de 14 anos de idade. As causas de PPT foram materno-fetais em 40,9%, ROPREMA em 29,7% e trabalho de parto prematuro em 29,4%. Na análise multivariada, ser casada foi um fator de proteção [OR = 12:48 (IC 95%: 0,24-0,97)]. Nenhuma das demais características foram associadas com a infecção por CT. Conclusões: Este estudo evidencia uma alta prevalência de infecção por CT entre parturientes com PPT. Essa alta prevalência reforça a necessidade da definição de estratégias de rastreamento e assistência durante o pré-natal.

Particulate bioglass in the regeneration of alveolar bone in dogs: clinical, surgical and radiographic evaluations

Bone loss, either by trauma or other diseases, generates an increasing need for substitutes of this tissue. This study evaluated Bioglass as a bone substitute in the regeneration of the alveolar bone in mandibles of dogs by clinical, surgical and radiological analysis. Twenty-eight adult dogs were randomly separated into two equal groups. In each animal, a bone defect was created on the vestibular surface of the alveolar bone between the roots of the fourth right premolar tooth. In the treated group, the defect was immediately filled with bioglass, while in the control, it remained unfilled. Clinical evaluations were performed daily for a week, as well as x-rays immediately after surgery and at 8, 14, 21, 42, 60, 90 and 120 days post-operative. Most animals in both groups showed no signs of inflammation and wound healing was similar. Radiographic examination revealed a gradual increase of radiopacity in the region of the defect in the control group. In the treated group, initial radiopacity was higher than that of adjacent bone, decreasing until 21 days after surgery. Then it gradually increased until 120 days after surgery, when the defect became undetectable. The results showed that Bioglass integrates into bone tissue, is biocompatible and reduced the period for complete bone regeneration.