A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis.

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease.

Quality assurance, benchmarking, assessment and mutual international recognition of qualifications.

The aim of this report is to provide guidance to assist in the international convergence of quality assurance, benchmarking and assessment systems to improve dental education. Proposals are developed for mutual recognition of qualifications, to aid international movement and exchange of staff and students including and supporting developing countries. Quality assurance is the responsibility of all staff involved in dental education and involves three levels: internal, institutional and external. Benchmarking information provides a subject framework. Benchmarks are useful for a variety of purposes including design and validation of programmes, examination and review; they can also strengthen the accreditation process undertaken by professional and statutory bodies. Benchmark information can be used by institutions as part of their programme approval process, to set degree standards. The standards should be developed by the dental academic community through formal groups of experts. Assessment outcomes of student learning are a measure of the quality of the learning programme. The goal of an effective assessment strategy should be that it provides the starting point for students to adopt a positive approach to effective and competent practice, reflective and lifelong learning. All assessment methods should be evidence based or based upon research. Mutual recognition of professional qualifications means that qualifications gained in one country (the home country) are recognized in another country (the host country). It empowers movement of skilled workers, which can help resolve skills shortages within participating countries. These proposals are not intended to be either exhaustive or prescriptive; they are purely for guidance and derived from the identification of what is perceived to be 'best practice'.

A qualitative analysis of the planning, implementation and management of a PDS scheme: lessons for local commissioning of dental services.

AIM: To identify the experiences of primary care trust employees, the dental teams and other key individuals of the planning, implementation and management of a Personal Dental Services scheme. METHOD: A thematic analysis of a series of qualitative interviews with 29 individuals who were involved in the planning, implementation and management of a PDS scheme in South East London. FINDINGS: Nine key themes were analysed from the data. For each theme perspectives could be identified for both the employees of the primary care trusts and the dental team. These perspectives differ in key respects. CONCLUSIONS: Practitioners value the PDS scheme and consider it a positive experience. They suggest that it has led to an increase in quality of care, and a more professional management approach to the practice. The practice team felt that they have benefited from an enhanced working environment. The main concern expressed was that patient registrations were not being accurately assessed. Those involved in the management of the PDS scheme, while endorsing local commissioning arrangements, were concerned that it was not known whether PDS was meeting local needs. There was little quality benchmarking, which would have allowed robust measure of success. The contract model and outcomes should have been more sensitively designed. There was concern expressed that the small number of practices who participated in the pilot scheme prohibits the possibility of thoroughly analysing the impact of local commissioning. Future local commissioning should identify mechanisms for ensuring the effective planning, management and evaluation of the impact of the schemes. A core element of this will be the specification of appropriate goals for commissioning.

Continuing professional development--global perspectives: synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 1: access, funding and participation patterns.

There appears to have been little previous research interest in continuing professional development (CPD) of dentists and the oral health team. This paper presents data and information on the following aspects of CPD in 17 countries in Asia, Australasia, Europe and North America: availability of different types of CPD, its providers, data on uptake of CPD courses and activities, and funding of CPD. The results indicate that lectures and hands-on skills courses were held in all 17 countries but the use of the Internet to deliver CPD was by no means universal. CPD was funded from a variety of sources including universities, governments and commercial companies. However, the only universal source of funding for CPD was dentists themselves. Data on participation were available from only three countries. Research issues based on these results will be listed in a second paper.

Continuing professional development--global perspectives: synopsis of a workshop held during the International Association of Dental Research meeting in Gothenburg, Sweden, 2003. Part 2: regulatory and accreditation systems and evidence for improving the performance of the dental team.

This paper is the second in a series of two that report on continuing professional development (CPD). Details of the informants and the methodologies used were reported in the first paper. This paper reports the data and information presented on the topics of regulatory and accreditation systems for CPD and evidence that CPD improves the performance of the oral health team. By June 2003, participation in CPD was mandatory in most of the states of the USA, all Canadian Provinces, the UK and Latvia and was likely to become mandatory in a number of other countries in the near future. A variety of accreditation systems were reported including collecting CPD points, which in some countries were weighted depending on the type of CPD activity, and re-certification examinations. Very few studies for the effectiveness of dental CPD were identified. However, in general it was concluded that there is little evidence for the effectiveness of CPD for the oral health team. The main recommendation from this study is that a systematic review of the effectiveness of CPD in improving the performance of the oral health team and patient based outcomes be undertaken. A range of other research questions was also identified including: how can CPD be best matched to clinicians' needs rather than demands?

Is the current access to health information helping or hindering effective decision-making for dentists and patients? Guidelines for dental practice.

With the introduction of the Internet there has been a growth both in the quantity and accessibility of information to the public concerning health issues. This improved availability of information does not always lead to a more informed public since there is no quality control of information but it can lead to a public that takes a more active role in their own health and thus is involved in shared decision-making. In order to develop a more informed public in the future, systems for quality control of information have been addressed. These systems can range from the present state of uncontrolled information (no quality control) to full-centralised control (censored information). Between these extremes lie two, more appropriate, decentralised filtering approaches--'upstream filtering' (where third parties set quality criteria and evaluate information) and 'downstream filtering' (where data are rated, labelled and weighted according to consumers' criteria). These systems of filtering are discussed along with recommendations for those using the Internet as a source of information. The paper also documents reliable sources of information for the public, highlights the current concepts of shared decision-making, and provides some guidelines for developing an effective decision-making strategy.

Professional development for dentists: patterns and their implications.

BACKGROUND: Approaches to models of professional development for dentists continue to evolve. This study examined the participation and attitudes of dentists in non-formal and informal professional development and continuing dental education. METHODS: Two methodologies were utilised: a self-administered cross-sectional survey of dentists in Victoria, Australia (conducted October to December, 1994), and a review of the records of the Continuing Education Unit of the School of Dental Science at The University of Melbourne for 1995 to 1999. For the cross-sectional survey, the sampling frame was the register of dentists of the Dental Board of Victoria in 1994. RESULTS: From a sample of 616 dentists invited to participate, 396 usable questionnaires were returned (response rate, 66.8 per cent). The valid data indicated that 52.5 per cent of dentists belonged to a study group, 66.5 per cent subscribed to at least one dental journal (other than the Australian Dental Journal), 88.9 per cent discussed dental matters with colleagues regularly, 98.6 per cent personally assessed their own work, 13.3 per cent did not attend continuing education courses and 18.1 per cent did not complete any courses in the year preceding the survey. Participation patterns in continuing education courses were related to socio-demographic characteristics of dentists. Some support was apparent for flexible delivery options for professional development. CONCLUSIONS: Involvement of dentists in Victoria, Australia in professional development activities is high, with complex participation patterns. Whether these patterns adequately address their own and the community's needs for such activities is debatable. Such issues should impact on any regulatory models for professional development for dentists and the development and use of alternative continuing education modalities.

Drawing specimens for coagulation testing: is a second tube necessary?

Three recent studies discussed the possibility that the National Committee for Clinical Laboratory Standards (NCCLS) recommendations that the coagulation specimen should be the second or third tube collected are unnecessary. However, only one reagent/instrument was used in each study. Our protocol differed from the previous studies because we performed the assays on three different reagent/instrument systems on the same samples. Our study used photo-optic, mechanical, and nephelometric systems of clot detection. After obtaining informed consent, we obtained two blue-stoppered tubes of blood from 95 subjects: 15 normal patients and 80 patients currently on coumadin therapy. No discard tube was drawn for coagulation testing. A prothrombin time with an international normalized ratio and an activated partial thromboplastin time, were performed on each tube. Laboratory One used a MLA 1600C (Hemoliance) with Thromboplastin DS (Pacific-Hemostasis, ISI of 1.11) and APTT-LS (Pacific-Hemostasis). Laboratory Two used an STA (Diagnostica-Stago) with Neoplastine CI+ (Diagnostica-Stago, ISI of 1.14) and PTT-LT (Diagnostica-Stago). Laboratory Three used an ACL 300 with Plastinex (Biodata, ISI of 1.67) and Actin FSL (Dade Behring). No clinical or statistically significant differences were seen between the first or second tubes on any of the three reagent/instrument combinations in the PT in seconds, international normalized ratio reporting, or APTT results. Our results indicate that the NCCLS guidelines for obtaining a second tube when performing coagulation testing should be considered for elimination when new revisions are published.

Strike contingency planning.

On Monday, February 26, 1996, the Ontario Public Service Employees Union (OPSEU) went on strike. The month-long strike included the 10 provincial psychiatric hospitals in Ontario. Within the psychiatric hospitals, the included direct care providers--RNs, RPNs, psychologists, social workers, occupational therapists--as well as support workers (food service, maintenance, housekeeping, and office employees). In anticipation, the mental health program at the London Health Science Centre (LHSC) developed a contingency plan that went into action when the strike was announced. This paper outlines the plan, describes what happened and makes recommendations for nurses who may be faced with similar situations.

Rapid removal of platelets from plasma utilizing the Hepcheck heparin removal filter.

We investigated whether Hepcheck heparin removal filters could remove residual platelets from platelet-poor plasma (PPP) without compromising samples for lupus anticoagulant (LA) testing. Furthermore we assessed what effect, if any, plasma filtration has on various clotting tests that form the foundation for LA testing. Citrated blood was obtained from 35 normal donors. Two sets of citrated tubes were processed in order to obtain PPP. Citrated blood was also obtained from a single donor to check the actual amounts of platelets removed by the Hepcheck filtration device. One set of PPP samples was filtered using the Hepchek filter device and the other was not processed, i.e. unfiltered. Prothrombin time (PT), activated partial thromboplastin time (APTT), and kaolin clotting time (KCT) were performed on both unfiltered and filtered samples that were tested immediately and after freezing at -70 degrees C for 24 h. Platelet counts on the single donor's citrated plasma were dramatically reduced after filtration. PT and APTT values showed small but statistically significant differences between unfiltered and filtered plasmas whether these were fresh or frozen samples. However, these differences were not clinically significant. KCT data showed statistical and clinical differences between unfiltered and filtered plasmas whether fresh or frozen plasmas were used. In contrast, KCT values were similar if unfiltered, fresh plasmas or filtered, frozen plasmas were used. Coagulation factor assays for factors VIII, IX and X were performed on both sets of PPP samples after freezing to determine if the filtration device affected these levels and would as a result, compromise APTT based lupus testing. Factor IX levels demonstrated a loss of activity following use of the device but no change was observed in factor VIII or factor X. Von Willebrand factor antigen and function as well as multimer structure were not affected by the filtration device in 10 normal donors. Filtering plasmas of two donors with a history of an LA dramatically prolonged clotting times for APTT, Dilute Viper Venom Time, mixing studies, and STACLOT LA tests in comparison with unfiltered plasmas. The data indicate that plasma filtration using the Hepchek device does not adversely affect coagulation testing. Furthermore samples requiring testing for the lupus anticoagulant can be filtered and subsequently frozen and compare favorably with freshly processed samples.

An experimental model for the assessment of titanium denture casting techniques.

In order to establish the most suitable technique for the construction of cast titanium denture frames, an experimental model was developed for the quantification of casting success. A relatively large wax pattern (36 x 29 x 0.9 mm) was prepared from a grid sheet used for the construction of cast cobalt chromium partial denture frames. The pattern consisted of 100 circles and the number of completely cast circles was counted to obtain a percentage success rate. The castings were complete with pure titanium but incomplete (average 54%) with a titanium alloy. For an inspection of internal defects the radiographic conditions were optimised by adopting a relative density of about 2.0. The procedures described will help in establishing the most suitable casting technique for the construction of titanium denture frames for any casting system employed in a laboratory.

Awareness and needs of dental implants by patients in New South Wales.

An exploratory cross-sectional analytical study of patients presenting for prosthodontic treatment to private general dental practices and public hospitals in New South Wales was completed. Significantly more patients attending private dentists had 'heard' of dental implants compared with the hospital group (G2=79.404; df=1; p<0.001) and significantly more of the former patients were aware that dental implant treatment is available in New South Wales (G2=32.823; df=1; p<0.001). Of the patients attending private practice 19.2% felt that it is likely that they may require dental implant treatment in the future and 14.1% of their current treatment requests involved implants. These figures may be considered moderately high whereas the corresponding figures for the patients attending public hospitals were low.

Mandibular overdenture treatment. Case report.

Complete mandibular dentures have a significantly lower success rate compared with complete maxillary dentures. Overdentures are feasible alternatives in many instances in attempting to achieve an optimal clinical result. The case of a 56-year-old female patient requiring prosthetic rehabilitation is discussed. A complete maxillary denture and a complete mandibular overdenture were constructed.

Measurement of active drag during crawl arm stroke swimming.

In order to measure active drag during front crawl swimming a system has been designed, built and tested. A tube (23 m long) with grips is fixed under the water surface and the swimmer crawls on this. At one end of the tube, a force transducer is attached to the wall of the swimming pool. It measures the momentary effective propulsive forces of the hands. During the measurements the subjects' legs are fixed together and supported by a buoy. After filtering and digitizing the electrical force signal, the mean propulsive force over one lane at constant speeds (ranging from about 1 to 2 m s-1) was calculated. The regression equation of the force on the speed turned out to be almost quadratic. At a mean speed of 1.55 m s-1 the mean force was 66.3 N. The accuracy of this force measured on one subject at different days was 4.1 N. The observed force, which is equal to the mean drag force, fits remarkably well with passive drag force values as well as with values calculated for propulsive forces during actual swimming reported in the literature. The use of the system does not interfere to any large extent with normal front crawl swimming; this conclusion is based on results of observations of film by skilled swim coaches. It was concluded that the system provides a good method of studying active drag and its relation to anthropometric variables and swimming technique.

Phenytoin induced gingival overgrowth in institutionalized epileptics.

In a cross-sectional, epidemiological study of phenytoin induced gingival overgrowth in 77 institutionalized persons with epilepsy, the severity of the gum lesions was quantified by means of a precise new technique. Lesion severity was then compared statistically to other clinical and laboratory parameters. Positive correlations were detected between overgrowth severity and gingival inflammation, probing depths, calculus accumulation, plaque score and the measurement gingival margin to mucogingival junction (GM-MGJ). No correlation was observed between lesion severity and patients age, daily drug dosage, plasma or saliva phenytoin level, or salivary concentration of the major phenytoin metabolite.

Salivary phenytoin levels in institutionalized epileptics.

Measurement of phenytoin (PHT) levels in saliva has been advocated as a monitor of plasma levels, and therefore of effective dosage. All studies to date have been performed on outpatients. We have now analyzed whole saliva from 62 mentally retarded, institutionalized, PHT-treated persons with epilepsy. Both PHT and its major human metabolite, 5-(para-hydroxyphenyl)-5-phenylhydantoin (pHPPH) were measured using gas-liquid chromatography. We detected large inter-individual variations in saliva PHT and pHPPH levels. Data were ranked and subjected to statistical analysis according to Spearman. Significant positive correlations were detected between daily PHT dose and plasma total PHT concentration, plasma PHT and salivary PHT, and daily dose and salivary PHT level. When data were categorized and analyzed according to the type of medication being administered in addition to PHT, different results were obtained. Polypharmacy can influence drug and metabolite levels and relationships in institutionalized persons with epilepsy.

Controlling the exotic diseases: 1. Isolation facilities.

The exotic diseases are highly virulent transmissible conditions that include Lassa fever, some viral hemorrhagic fevers, smallpox and plague. Any of these diseases could be brought into or diagnosed in Canada as the result of natural or laboratory acquired infection. The patients must be isolated until the presumptive diagnosis is proved. High-security isolation is necessary and needs to be backed up by high-security laboratory services. In Canada facilities for high-security isolation are generally not available; therefore, hospitals must preplan and be ready to effect the best possible isolation under the existing conditions. The plan should address construction, ventilation, filtration, temperature and humidity, together with protective measures for staff and careful handling of laboratory specimens. Materials the patient has contacted and areas or vehicles he or she has been in will have to be decontaminated, and appropriate, safe disposal of corpses must be considered.

Controlling the exotic diseases: 2. Nursing management.

Advance planning can facilitate the care of a patient with an exotic disease who is admitted to a hospital that lacks facilities for high-security isolation. The Department of National Health and Welfare contingency plan for dealing with such patients lacks specific information in a number of areas of medical care, as described in this paper. Consideration must be given to the number of personnel trained and readied for employment, the criteria for selection and special preparation. The protective clothing generally used for hospital isolation procedures is inadequate. Several types of special clothing, including a respirator, are available for total protection of personnel; the clothing may be uncomfortable when worn for long periods, and does restrict movement, vision and communication. All persons entering the isolation suite must change into fully protective clothing, and double layers of clothing are required for direct patient care. All personnel must shower and change before leaving the isolation suite. Suitable facilities for dressing and showering, together with entry and exit routines, must be considered. Hand washing, daily cleaning procedures and disposal of liquid and solid wastes all require special procedures. The social and psychologic problems of patients and their families must also be considered. Preplanning is required to decrease the risks involved in monitoring vital signs and implementing emergency procedures requiring contact with the patient's blood.