Review of molecular subtyping methodologies used to investigate outbreaks due to multidrug-resistant enteric bacterial pathogens in sub-Saharan Africa

Background: In sub-Saharan Africa, molecular epidemiological investigation of outbreaks caused by antimicrobial-resistant enteric bacterial pathogens have mostly been described for Salmonella species, Vibrio cholerae, Shigella species and Escherichia coli. For these organisms, I reviewed all publications describing the use of molecular subtyping methodologies to investigate outbreaks caused by multidrug-resistant (MDR) enteric bacterial infections.Objectives: To describe the use of molecular subtyping methodologies to investigate outbreaks caused by MDR enteric bacterial pathogens in sub-Saharan Africa and to describe the current status of molecular subtyping capabilities in the region. Methods: A PubMed database literature search (English language only) was performed using the search strings: 'Africa outbreak MDR', 'Africa outbreak multi', 'Africa outbreak multidrug', 'Africa outbreak multi drug', 'Africa outbreak resistance', 'Africa outbreak resistant', 'Africa outbreak drug', 'Africa outbreak antibiotic', 'Africa outbreak antimicrobial'. These search strings were used in combination with genus and species names of the organisms listed above. All results were included in the review. Results: The year 1991 saw one of the first reports describing the use of molecular subtyping methodologies in sub-Saharan Africa; this included the use of plasmid profiling to characterise Salmonella Enteritidis. To date, several methodologies have been used; pulsed-field gel electrophoresis analysis and multilocus sequence typing have been the most commonly used methodologies. Investigations have particularly highlighted the emergence and spread of MDR clones; these include Salmonella Typhi H58 and Salmonella Typhimurium ST313 clones. In recent times, whole-genome sequencing (WGS) analysis approaches have increasingly been used. Conclusion: Traditional molecular subtyping methodologies are still commonly used and still have their place in investigations; however, WGS approaches have increasingly been used and are slowly gaining a stronghold. African laboratories need to start adapting their molecular surveillance methodologies to include WGS, as it is foreseen that WGS analysis will eventually replace all traditional methodologies

Legislation an essential tool for ensuring access to medicines policy goals.

Effective national legislation is critical to support the activities of a Medicines Regulatory Authority. However, the law is an under-recognized mechanism for managing issues in the implementation of access to medicines and other medicines policy goals. Regulations are a more flexible tool, have legal effect and the advantage that they can be created or changed without the need to go to the Parliament. Closer collaboration between the health and legal sectors is important as is political commitment for enforcement of the law. Some regional case studies illustrate the opportunities to use the law as an effective tool to implement medicine policies and to meet access to medicine challenges.

Telemedicine and rural health care applications.

Telemedicine has the potential to help facilitate the delivery of health services to rural areas. In the right circumstances, telemedicine may also be useful for the delivery of education and teaching programmes and the facilitation of administrative meetings. In this paper reference is made to a variety of telemedicine applications in Australia and other countries including telepaediatrics, home telehealth, critical care telemedicine for new born babies, telemedicine in developing countries, health screening via e-mail, and teleradiology. These applications represent some of the broad range of telemedicine applications possible. An overriding imperative is to focus on the clinical problem first with careful consideration given to the significant organisational changes which are associated with the introduction of a new service or alternative method of service delivery. For telemedicine to be effective it is also important that all sites involved are adequately resourced in terms of staff, equipment, telecommunications, technical support and training. In addition, there are a number of logistical factors which are important when considering the development of a telemedicine service including site selection, clinician empowerment, telemedicine management, technological requirements, user training, telemedicine evaluation, and information sharing through publication.

Paraproteins: a regional South Australian experience.

We have performed a systematic review of all new serum and urinary paraproteins detected over a six year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses and associated laboratory features were ascertained from a computerized laboratory database or from clinical notes. Over the period of study, serum or urine paraproteins were detected in 613 new patients. These consisted of 568 patients with serum paraproteins and 45 patients with urinary monoclonal free light chain (in the absence of a serum paraprotein). These paraproteins occurred more commonly in males and the frequency increased with age. Approximately 30% of the serum paraproteins and 60% of urinary monoclonal free light chain were associated with B cell lymphoproliferative disorders (multiple myeloma, plasmacytoma, Waldenstrom's macroglobulinemia, non-Hodgkins lymphoma, chronic lymphocytic leukemia, etc) with the remainder being labeled as monoclonal gammopathies of uncertain significance (MGUS). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of paraprotein, B2 microglobulin, the presence of free urinary light chain and demonstrated molecular size heterogeneity of the paraprotein but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. In conclusion paraproteins were most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of serum paraprotein (> 15 g/l), elevated levels of B2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen with patients with MGUS, regular monitoring of paraprotein level is considered mandatory in the management of these patients.

Acetylcholinesterase release from crude mitochondrial fractions and superfused synaptosomes of rat hypothalamus / Liberatión de acetilcolinesterarasa de la fracción mitocondrial cruda y de sinaptosomas superfundidos de hipotalamo de rata

Crude mitochondrial fractions of rat hypothalamus, incubated in oxygenated Krebs solution (37ºC), released acetylcholinesterase (AChE) (increased of enzyme activity) into the medium, upon depolarization by 50 mM K+;this effect was absent in Ca²+ free medium. Superfused-synaptosomes obtained from subfractionated crude mitochondrial fractions of rat hypothalamus also released AChE, in a calcium-dependent fashion, when dependent fashion, when depolarized by 50 mM K+ or 50 µM veratridine. The veratridine-releasing effect was antagonized by 2 mM tetrodotoxin. Lactic dehydrogenase activity did not change in the medium with the introduction of depolarizing substances