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Corneal wound healing is a complex process: its mechanisms and the underlying genetic control are not fully understood. It involves the integrated actions of multiple growth factors, cytokines and ...proteases produced by epithelial cells, stromal keratocytes, inflammatory cells and lacrimal gland cells. Following an epithelial insult, multiple cytokines are released triggering a cascade of events that leads to repair the epithelial defect and remodelling of the stroma to minimize the loss of transparency and function. In this review, we examine the literature surrounding the genomics of corneal wound healing with respect to the following topics: epithelial and stromal wound healing (including inhibition); corneal neovascularisation; the role of corneal nerves in wound healing; the endothelium; the role of aquaporins and aptamers. We also examine the effect of ectasia on corneal wound healing with regard to keratoconus and following corneal surgery. A better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design treatments that selectively modulate key phases of the healing process resulting in scars that more closely resemble normal corneal architecture.
These guidelines are a consensus document developed by a working party of the Australian and New Zealand Anaesthetic Allergy Group (ANZAAG) to provide an approach to the investigation of ...perioperative anaphylaxis. They focus primarily on the use of skin testing as it is the investigation with the greatest clinical utility for the identification of the likely causative agent and potentially safer alternatives. The practicalities and process of skin testing, its limitations, and the place of other tests are discussed. These guidelines also address the roles of graded challenge and in vitro testing. The implications of anaphylaxis associated with neuromuscular blocking agents, beta-lactam antibiotics, local anaesthetic agents and chlorhexidine are discussed. Evidence for the recommendations is derived from literature searches using the words skin test, allergy, anaphylaxis, anaesthesia, and each of the individual agents listed in these guidelines. The individual articles were then reviewed for suitability for inclusion in these guidelines. Where evidence was not strong, as is the situation for many perioperative agents, expert consensus from the ANZAAG working party was used. These guidelines are intended for use by specialists involved in the investigation of perioperative allergy. They have been approved following peer review by members of ANZAAG and are available on the ANZAAG website: http://www.anzaag.com/anaphylaxis-management/testing-guidelines.pdf.
A literature review to describe the current diagnosis and management of Acanthamoeba keratitis.
Acanthamoeba is a ubiquitous protozoan: 8 species, 5 genotypic classes have been reported to cause ...keratitis. It is potentially a sight-threatening infection, and there is often a poor prognosis because of a significant delay in diagnosis and frequently a lack of effective medical management. Main risk factors are contact lens wear, poor hygiene, and contact with contaminated water. Current methods of diagnosis include corneal scrapings for histopathologic analysis, tissue culture, confocal microscopy, and polymerase chain reaction (PCR), each are reviewed in turn. Treatment options include medical (biguanides, diamidines, and corticosteroids) and surgical (epithelial debridement, amniotic membrane transplant, and penetrating keratoplasty).
Early diagnosis and treatment are required to effectively manage this condition.
•A broth dilution procedure for AST of Brachyspira species is described.•The broth dilution method was validated in a ring trial.•Intra- and inter-laboratory reproducibility was good.•New control ...strains are proposed.•Increased MIC corresponded to genomic data indicating decreased susceptibility.
Brachyspira hyodysenteriae and Brachyspira pilosicoli cause economically important enteric disease in pigs. Treatment of these infections often includes antimicrobial administration, which can be most effective when therapeutic options are informed by antimicrobial susceptibility testing data. Here we describe a method for broth dilution antimicrobial susceptibility testing of these bacteria, both of which are difficult to culture in vitro. The protocol was evaluated for its fitness for use in an inter-laboratory ring trial involving eight laboratories from seven countries, and employing eleven test strains (5 Brachyspira hyodysenteriae including the type strain B78T and 6 Brachyspira pilosicoli) and six antibiotics. Overall intra- and inter-laboratory reproducibility of this method was very good (>90 % MICs at mode +/- 1 log2). Whole genome sequencing revealed good correspondence between reduced susceptibility and the presence of previously defined antimicrobial resistance determinants. Interestingly, lnu(C) was identified in B. pilosicoli isolates with elevated MICs of lincomycin, whilst tva(B) was associated with elevated MICs of pleuromutilins in this species. We designated two new control strains with MICs lying within currently tested ranges, including for the pleuromutilins, in contrast to the control strain B. hyodysenteriae B78T. These were deposited at the DSMZ-German Collection of Microorganisms and Cell Cultures GmbH. The validation of a standard protocol and identification of new control strains facilitates comparisons between studies, establishment of robust interpretative criteria, and ultimately contributes to rational antimicrobial use when treating infected livestock.
Objective
To assess the impact of large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN) on cervical morphology as assessed by three‐dimensional ...ultrasound.
Design
Prospective observational study.
Setting
University Hospital in Dublin.
Population
Women with CIN who underwent an LLETZ procedure.
Methods
All 106 participants had a three‐dimensional transvaginal ultrasound scan (3DTVS) performed immediately before and 6 months after LLETZ. The excised LLETZ specimen dimensions were also recorded. Blind analysis of the images was performed. The volume of the uterus and cervix was documented.
Main outcome measures
The relationship between the extirpated LLETZ dimensions and subsequent cervical and uterine biometry, as assessed by 3DTVS.
Results
LLETZ induced a statistically significant reduction in both the length (mean, –0.46 cm; P < 0.001) and the volume (–6.12 cm3; P < 0.001) of the uterus, and in the volume of the cervix (–1.60 cm3; P < 0.001). The volume of the excised specimen had a significant impact on the reduction of the length of the uterus (β, –0.038; P = 0.012), the volume of the uterus (β, –0.791; P = 0.036) and the volume of the cervix (β, –0.121; P = 0.046). The circumference of the excised specimen appeared to have a significant impact on the length (β, –0.016; 95% CI, –0.028 to –0.003; P = 0.013) and volume (β, –0.413; 95% CI, –0.719 to –0.107; P = 0.009) of the uterus 6 months after LLETZ.
Conclusions
The volume of tissue removed at LLETZ is related to the subsequent cervical volume, as well as the uterine length and volume, 6 months after the procedure.
To report a series of 4 cases (3 patients) with late stromal graft rejection 32 to 46 months after an uneventful deep anterior lamellar keratoplasty (DALK).
Three patients (4 eyes), who had undergone ...an uneventful DALK for keratoconus (3 eyes) and infectious keratitis (1 eye) 32 to 46 months previously presented with a history of ocular discomfort and redness, with reduced visual acuity in 3 eyes. In all cases, all sutures had been removed at least 18 months previously. On examination, there was superficial and in 2 eyes deep neovascularization. In 2 eyes, the vessels extended within the interface between the donor and host corneas. The stroma of the donor cornea adjacent to the areas of vascularization was edematous. A diagnosis of stromal graft rejection was made, and the patients were administered intensive topical corticosteroids.
All eyes responded well to treatment, becoming more comfortable, with decreasing redness, reversal of corneal edema, and return of prerejection best corrected visual acuity with up to 18 months follow-up. The patients continued to receive tapering dosage of topical corticosteroid for 12 months. In 1 eye topical steroids were reintroduced at 13 months because of a further rejection episode.
These cases of late stromal rejection after DALK provide clinical evidence that donor keratocytes may persist in such lamellar grafts for extended periods and that patients should be warned that rejection may occur years after surgery.
Risk assessment of chemicals in food is generally based upon the results of toxicological studies in laboratory animals, allowing for uncertainties relating to interspecies differences, human ...variability, and gaps in the database. Use of quantitative human data is preferable if available, as in the example of methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which fish is the main source of dietary exposure. Human data from poisoning incidents and epidemiological studies have been used by expert committees to derive a guideline intake level for methylmercury, based on the susceptibility of the most sensitive lifestage, the developing fetus.
In the UK, an expert group of nutritionists and toxicologists was formed to review the benefits and risks associated with fish consumption. A formal risk–benefit analysis was not possible because the nutritional data were not sufficiently quantitative. The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT), therefore, modified the risk assessment approach to derive different guideline intake levels for different subgroups of the population. The COT opinion was used to provide targeted advice on how much fish can be consumed without undue risk from the contaminants.
Consumption by adults of one weekly portion (140 g) of shark, swordfish or marlin, would lead to an exceedance of the guideline intake for methylmercury of 40–90%, set to protect the developing fetus, without considering intake from the rest of the diet. Pregnant women and women who may become pregnant within 1 year were, therefore, advised to avoid consumption of these species. Intakes in other adults would be within a higher guideline intake, set to protect groups of the population other than the developing fetus. However, consumption by children of one weekly portion of these species could lead to an exceedance of this guideline intake by up to 60%, without considering intake from the rest of the diet. It was, therefore, advised that consumption of these species by children should be avoided.
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