This is the first study to compare the relative concentration-time data of bolus and continuous administration of meropenem at the subcutaneous tissue and plasma levels. We found that the administration of meropenem by continuous infusion maintains higher concentrations in subcutaneous tissue and plasma than by intermittent bolus dosing. Administration by extended or continuous infusion will achieve superior CFR against less-susceptible organisms in patients without renal dysfunction.

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Patients with sepsis do not seem to have the same level of impairment of tissue distribution as described for patients with septic shock. A 25% lower dose of piperacillin administered by continuous infusion seems to maintain higher trough concentrations compared with standard bolus dosing. It is likely that the clinical advantages of continuous infusion are most likely to be evident when treating pathogens with high minimum inhibitory concentration, although without therapeutic drug monitoring and subsequent dose adjustment, infusions may never achieve target concentrations of organisms with very high minimum inhibitory concentrations in a small number of patients.

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The importance of a dermal element when providing permanent wound cover for skin loss has become evident as the shortcomings of pure epidermal grafts are recognized. We are developing a skin composite formed from sterilized human de-epidermized acellular dermis, keratinocytes and fibroblasts with the ultimate aim of using this composite to cover full-thickness excised burn wounds. These composites can be prepared with or without basement membrane (BM) antigens initially present on the dermis. This study investigates the importance of retaining BM antigens on the dermis to the production and appearance of these composites in vitro. Skin composites prepared from dermis with BM antigens either present or absent initially were studied throughout 3 weeks. Composites with BM antigens present initially were significantly better than those initially lacking BM antigens in: (i) the degree of epithelial cell attachment to the underlying dermis (hemidesmosomes were seen only in the former); (ii) the morphology of the epithelial layer; (iii) the consistent presence of collagen IV and laminin and the increasing expression of tenascin; and (iv) the amount of soluble collagen IV and fibronectin detected in the conditioned media. We conclude that an initial BM antigen template is vital in this skin composite model for the attachment and differentiation of the epithelial layer and for the subsequent remodelling of the BM in vitro.

We conclude that the measurements of urinary collagen III (PIIINP), and to a lesser extent serum collagen III (PIIINP), are useful indicators of the extent of renal fibrosis. This may have diagnostic implications and may prove useful for the monitoring of disease progression.

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Resection to NBI-defined margins will leave less dysplastic and malignant residual tissue and thereby increase ablative surgery success rates. © 2015 Wiley Periodicals, Inc. Head Neck 38: 832-839, 2016.