The response of the host microcirculation to bacterial sepsis: Does the pathogen matter?

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte-endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis

Phase II evaluation of MGBG in non-small cell carcinoma of the lung

One hundred and eight patients with non-small cell lung cancer were treated in a Phase II trial with MGBG at a dose of 600 mg/m 2 i.v. weekly. Partial responses were noted in 3/43 patients with adenocarcinoma and 1/40 with squamous cell carcinoma. No responses were noted in 24 patients with large cell carcinoma. Overall, the drug was reasonably well-tolerated. At this dosage and schedule, MGBG has no substantial antitumor activity for patients with non-small cell lung cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45128/1/10637_2004_Article_BF00180196.pd

Psychological distress at follow-up after major surgery for intra-oral cancer.

A cohort of patients who had received major intra-oral surgery, up to 10 yr (mean 3.5 yr) prior to this study were reviewed and assessed for evidence of current psychological disturbance. Forty-one per cent of patients were found to have significant levels of psychological distress comprising mood disorder, social dysfunction or both types of difficulty. Prevalence of clinical anxiety and depression per se was within the range 22-32%, but few patients were receiving any form of active therapy for these problems. Investigation of predictors revealed that females and younger people were more at risk to psychological distress. Tentative evidence for variability in psychological outcome in relation to tumour site is also reported. Results are discussed with reference to service provision needs and further research priorities

Functional implications of major surgery for intraoral cancer.

A group of 41 patients were questioned about functional problems and concern for appearance, experienced following major surgery for intraoral malignancy. Twenty-five per cent of the group reported significant difficulties. Spouses reported a higher incidence of problems. The effects of primary tumour site and type of reconstruction on functional outcome are discussed

The requirement for basement membrane antigens in the production of human epidermal/dermal composites in vitro

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

Keratinocytes contract human dermal extracellular matrix and reduce soluble fibronectin production by fibroblasts in a skin composite model

Composites of human de-epidermised acellular dermis and normal adult human keratinocytes and fibroblasts were examined for the ability of cells to contract these composites. Image analysis of the outline of the composites showed that, in this model, keratinocytes alone or in the presence of fibroblasts caused highly significant contraction (of the order of 25% by day 12). There was no significant contraction of the dermis with libroblasts alone or in the absence of cells. The presence or absence of basement membrane antigens did not influence the effect of keratinocytes on dermal contraction. Analysis of the conditioned media from these composites showed that the greatest fibronectin production was seen with fibroblasts alone in the presence of basement membrane. Keratinocytes alone produced little libronectin irrespective of the presence of the basement membrane. If keratinocytes were present with libroblasts, however, then libronectin production was significantly reduced both in the presence and absence of the basement membrane, indicating that keratinocytes modify dermal libroblast extracellular matrix production. This study shows that while keratinocytes and fibroblasts are clearly influencing each other’s activity in this human skin composite model, under the circumstances we describe it is the keratinocyte and not the libroblast which causes contraction of the human de-epidermised acellular dermis