A prospective diagnostic study on povidone-iodine retention in lesions suspected to be squamous cell carcinoma or keratoacanthoma.

BACKGROUND AND OBJECTIVES: While dermatoscopy improves diagnostic accuracy for raised nonpigmented lesions, those with white surface keratin can be problematical. We investigated whether retention of povidone-iodine by surface keratin provides a clue to benignity. METHODS: We performed a retrospective pilot study (n = 57) followed by a prospective study (n = 117) on raised nonpigmented lesions with white surface keratin. An initial dermatoscopic image was taken of each lesion, povidone-iodine was applied and another image taken. Following lavage with 70% ethanol, a third image was acquired. The percentage surface area of residual povidone-iodine staining after lavage was recorded, and the results analysed. RESULTS: The optimal cut-off point of residual staining was 80%, where values of ≤80% pointed to malignancy. At this cut-off, the OR for lesions with values ≤80% to be truly malignant in the retrospective set was 4.03 (95% CI: 2.1-7.6) and the AUC was 0.7 (95% CI: 0.62-0.78). For the prospective set, the corresponding OR was 2.3 (95% CI: 1.4-3.7) and the AUC was 0.62 (95% CI: 0.55-0.68). CONCLUSIONS: This study presents evidence that povidone-iodine retention may have a degree of efficacy in distinguishing benign from malignant keratotic lesions. Further study is warranted.

Conservative management of type II and III odontoid fractures in the elderly at a regional spine centre: A prospective and retrospective cohort study.

BACKGROUND: The optimal management of odontoid fractures in the elderly population is unclear and management of this group of patients is complicated by multiple co-morbidities. This study aimed to determine the outcomes after conservative management strategies were applied in this patient group. METHODS: We carried out retrospective and prospective analyses of all patients with axial cervical spine injuries, at a single centre. We included patients aged over 60 years with type II and III odontoid fractures. Information was gathered on demographics, ASA grading-associated injuries and complications. The outcome measures were rates and type of union, pain and neurological functions, specifically ambulation. RESULTS: Fifty-seven adult patients with a median age of 78 years (range 60-92 years) were included. There were 42 type II and 15 type III odontoid fractures. Three patients required surgical fixation due to displaced fractures, which could not be reduced with manual traction. Twenty-four (41%) patients were managed with a rigid pinned halo orthosis to obtain adequate reduction and immobilisation. The remaining 30 (53%) were managed in a hard cervical collar. Patients managed with a halo were significantly younger and had more associated injuries than patients managed in a collar (age: t-test=4.05, p<0.01, associated injuries: Chi-square=4.38, p<0.05). At a mean follow-up of 25 weeks, 87% of type II and 100% of type III fractures had achieved bony union or stable, fibrous non-union. There were no statistical differences in fracture type, follow-up or neurological outcomes between the halo and collar groups. However, overall more patients managed in a collar developed stable fibrous non-union than bony fusion (Fisher's exact test, p<0.05), although this was not significant when analysed by each fracture type individually. A regression model was constructed and identified fracture type as the only independent predictor of time to union, with type III fractures healing faster than type II. CONCLUSIONS: High rates of bony union and stable fibrous non-union with a good functional outcome can be achieved in the elderly population sustaining type II or III odontoid fractures, when managed non-surgically. Halo orthosis may not offer any clear advantage over hard collar in this group. Close follow-up is needed for late complications and there must be a willingness to perform surgery if conservative measures fail.

A proposed method for retrospective eye dose assessments for the purposes of resolving cataract compensation claims.

The 2011 International Commission on Radiological Protection (ICRP) statement on tissue reactions suggested a significant reduction in the threshold dose for radiation induced cataracts. This, combined with the potential for a long delay between exposure and cataract diagnosis, may result in an increased requirement to evaluate eye dose from past exposures in order to settle current compensation claims. This article highlights how compensation claims relating to radiation exposure are assessed within the UK legal system and suggests that in vivo Electro Paramagnetic Resonance (EPR) dosimetry of teeth has utility for the retrospective quantification of radiation doses to the eye. It was identified that in vivo EPR in its current form may be sufficiently sensitive to support cataract compensation claims, although further work is required to enable appropriate dose conversion coefficients to be quantified.

Radiologic assessment of spinal fusion.

Since surgical fusion of the spine was first described in 1911, multiple methods have been used to assess it. Although open surgical exploration remains the standard of care for determination of fusion, it is impractical in most clinical situations. Static radiographs have long been used as a practical method of fusion assessment, but they tend to significantly overestimate the presence of a solid fusion. Dynamic radiographs improve accuracy but limitations include measurement reliability, disagreement on allowable motion, and the two-dimensional nature of radiographs. Ultimately, lack of movement at a fused segment does not confirm fusion. Radiostereometric analysis further improves accuracy; however, methodological demands make it largely impractical for routine use. CT is now widely accepted as the standard for noninvasive assessment of spinal fusion. Fine-cut imaging, multiplanar reconstruction, and metal artifact reduction have increased the ability to assess fusion on CT. However, significant concerns remain regarding the effects of high radiation exposure. Although MRI is appealing, its utility in assessing fusion remains unproven. Understanding the limitations of each technique allows judicious use of radiology in the assessment of spinal fusion.

Immunogenicity of orally-delivered lipid-formulated BCG vaccines and protection against Mycobacterium tuberculosis infection.

Lipid formulations containing BCG strains Danish 1331 or Moreau (Rio de Janeiro) were trialled as oral vaccines in rodent models. In mice, oral-delivery of either strain resulted in BCG colonisation of the alimentary tract lymphatics and induction of gamma-interferon responses. In guinea pigs, both strains provided pulmonary protection against Mycobacterium tuberculosis aerosol challenge, as shown by significantly reduced bacterial loads and lung:body weight ratios. Lipid-formulated BCG provided superior protection against M. tuberculosis over unformulated orally-delivered BCG (Moreau), and equivalent protection to sub-cutaneous BCG (Danish) immunisation. Oral-delivery of lipid-formulated BCG may offer a practical alternative to parenteral-route BCG vaccination.

Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis.

The bacillus Calmette Guérin (BCG) vaccine, the only licensed vaccine against TB, displays partial and variable efficacy, thus making the exploitation of novel vaccination strategies a major priority. Most of the current vaccines in pre-clinical or clinical development are based on the induction of T cells recognizing protein antigens. However, a large number of T cells specific for mycobacterial lipids are induced during infection, suggesting that lipid-based vaccines might represent an important component of novel sub-unit vaccines. Here, we investigated whether immunization with defined mycobacterial lipid antigens induces protection in guinea pigs challenged with M. tuberculosis. Two purified mycobacterial lipid antigens, the diacylated sulfoglycolipids (Ac2SGL) and the phosphatidyl-myo-inositol dimannosides (PIM2) were formulated in biophysically characterized liposomes made of dimethyl-dioctadecyl-ammonium (DDA) and synthetic trehalose 6,6'-dibehenate (TDB). In three protection trials, a reduction of bacterial load in the spleen of inoculated animals was consistently observed compared to the unvaccinated group. Moreover, a reduction in the number of lesions and severity of pathology was detected in the lungs and spleen of the lipid vaccine group compared to unvaccinated controls. As the degree of protection achieved is similar to that observed using protein antigens in the same guinea pig model, these promising results pave the way to future investigations of lipid antigens as subunit vaccines.

Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix.

A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease.

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.