Clinical outcomes and inflammatory response to single-incision laparoscopic (SIL) colorectal surgery: a single-blinded randomized controlled pilot study.

AIM: Single-incision laparoscopic (SIL) surgery is expanding, but its benefits, efficacy and safety compared with conventional laparoscopic (CL) surgery remain unclear. This pilot study examined clinical outcomes and biochemical markers of inflammation for colorectal resections by SIL and CL in a randomized controlled pilot trial. METHOD: Fifty patients undergoing elective colorectal resection were randomized to either SIL or CL. Primary outcomes were operating time and length of stay (LoS); secondary outcomes included combined length of scars, pain scores, complications, Quality of Life EQ5D-VAS and the inflammatory markers interleukin-6 (IL-6), IL-8 and C-reactive protein (CRP) at baseline, 2, 6, 24 and 72 h. RESULTS: There was no difference in age, gender, body mass index, indications and site of surgery, American Society of Anesthesiologists grade or incidence of previous surgery between the groups. Except for one conversion from SIL to open surgery, surgery was completed as intended. No difference between SIL and CL was found for operating time [median 130 (72-220) vs 130 (90-317) min, respectively, P = 0.528], LoS [median 4 (3-8) vs 4 (2-19)days, P = 0.888] and time to first flatus [2 (1-4) vs 2 (1-5) days, P = 0.374]. The combined length of scars was significantly shorter for SIL [4 (2-18) vs 7 (5-8) cm, P < 0.001]; in each group, four postoperative complications occurred (16%). Postoperative pain scores were similar [mean 7.67 (interquartile range 4) vs 7.25 (interquartile range 3.75), P = 0.835] to day 3. EQ5D-VAS was no different for both groups at discharge [72.5 (40-90) vs 70 (30-100), P = 0.673] but slightly higher for CL at 3 months [79 (45-100) vs 90 (50-100), P = 0.033].The IL-6, IL-8 and CRP levels between both groups showed similar peaks and no significant differences. CONCLUSION: SIL colorectal surgery by experienced laparoscopic surgeons appears to be safe and equivalent to CL, with no discernible difference in its effect on the physiological response to surgical trauma.

The effect of education plus access on perceived fruit and vegetable consumption in a rural African American community intervention.

African Americans have an increased risk of cardiovascular disease partly due to low fruit and vegetable consumption. This article reports the results of an intervention to provide nutrition education and access to fruits and vegetables through community gardens to change dietary behaviors among African Americans in rural Missouri. Cross-sectional surveys evaluated the intervention effect on blood pressure, body mass index (BMI), and perceived fruit and vegetable consumption in this quasi-experimental study with a comparison group. Hypertension (OR = 0.52, 95% CI: 0.38-0.71) and BMI (OR = 0.73, 95% CI: 0.52-1.02) were lower in the intervention county at mid-intervention. Participation in nutrition education (OR = 2.67, 95% CI: 1.63-4.40) and access to fruits and vegetables from a community garden (OR = 1.95, 95% CI: 1.20-3.15) were independently associated with perceived fruit and vegetable consumption. The strongest effect on perceived fruit and vegetable consumption occurred with high participation in nutrition education and access to community gardens (OR = 2.18, 95% CI: 1.24-3.81). Those with access but without education had a reduced likelihood of consuming recommended servings of fruits and vegetables (OR = 0.57, 95% CI: 0.34-0.95). Education plus access interventions may be best at increasing consumption of fruits and vegetables in a rural African American population.

Plasminogen activator system in oral squamous cell carcinoma.

BACKGROUND: The plasminogen activator system consists of two plasminogen activators, urokinase (uPA) and tissue (tPA); PA inhibitors (PAI-1, and -2), and a cell surface receptor for uPA (uPAR). The plasminogen activator system is involved at many stages of the metastatic cascade, including matrix remodelling, cell proliferation, and migration. AIMS: To compare tissue concentrations of the components of the plasminogen activator system in paired tumour tissue and normal tissue in patients with oral squamous cell carcinoma, and to correlate these with the histopathological grading of the tumour. METHODS: Thirty-eight paired tissue samples were analysed by enzyme-linked immunosorbent assays (ELISA; ng/mg protein) for uPA, tPA, uPAR, PAI-1, and PAI-2. RESULTS: Concentrations of uPA, uPAR, PAI-1, and PAI-2 were significantly higher in tumour than in normal oral tissue (median in uPAR tumour 1.6 (range; 0.1-7.5) ng/mg protein; normal=0.2 (0-2.3), p<0.05). There were strong correlations between the concentrations of certain components of the plasminogen activator system in particular between uPA, uPAR, and PAI-1 (p<0.05). Tissue concentrations of some components of the plasminogen activator system correlated with clinical and pathological indexes of aggression of tumours, including differentiation and T-stage. CONCLUSION: The relation between components of the plasminogen activator system, in particular uPA, uPAR, and PAI-1 in invasion, metastasis, prognosis, and survival, requires further investigation in oral squamous cell carcinomas.

The matrix metalloproteinase system in oral squamous cell carcinoma.

BACKGROUND: The matrix metalloproteinase (MMP) system is responsible for degradation of tissue in both normal and pathological processes, including tumour invasion and metastasis. AIM: To compare tissue concentrations of components of the MMP system between tumour tissue and normal tissue in patients with oral squamous cell carcinoma, and to correlate concentrations with pathological grade of tumour. METHODS: Thirty-eight paired tissue samples from tumours and normal tissue were analysed by three laboratory techniques: firstly, enzyme linked immunosorbent assays (ELISA) in ng/mg protein for MMP-1, MMP-3, and tissue inhibitors of metalloproteinases (TIMPs) -1 and -2. Secondly, gelatinase activity assays to measure concentrations of total and endogenous active gelatinases, MMP-2 and MMP-9 (ng/mg protein). And thirdly to use quenched fluorescent substrate hydrolysis to measure total MMP activity (pM/min). RESULTS: The concentration of all MMPs was significantly higher in tumour than in normal oral tissue (p < 0.05, Mann-Whitney U-test). Tissue concentrations of some of these factors correlated with clinical and pathological indices of aggressiveness of tumours, including T-stage, N-stage, tumour differentiation, and anatomical level of involved nodes. However, the study was not powered to show statistical significance. CONCLUSION: It is the balance between proteinases and their inhibitors that controls tissue degradation at each stage of tumour invasion and metastasis. Measurement of MMPs in oral mucosal biopsy samples may establish the invasive potential of tumours at their initial presentation.

The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology.

The aim of this study was to determine the expression of proteinases and inhibitors from the matrix metalloproteinase (MMP) (MMPs 1, 2, 3, 9, tissue inhibitors of metalloproteinases (TIMPs) 1, 2) and plasminogen activator ((PA) urokinase (uPA), tissue type (tPA), uPAR, plasminogen activator inhibitors (PAIs) 1, 2) systems in colorectal cancer pathology by gelatin zymography, enzyme-linked immunosorbent assays (ELISAs) and quenched fluorescent substrate hydrolysis. The levels of all studied MMPs, uPA, uPAR, TIMP-1 and PAIs were significantly greater in tumour tissues than normal tissues. However, tPA and TIMP-2 were greater in normal colon (P<0.05, Mann-Whitney) e.g. PAI-1: tumour, median 14.9 (range 0.2-80.2) ng/mg total protein; normal, 2.1 (0.1-65.0). Tumour levels of several factors, in particular MMP-1 and PAI-1, correlated with pathology, i.e. Dukes' stage, differentiation, lymphatic or vascular invasion and tumour depth. The interactions between proteinase systems in colorectal cancer are complex and the balance between active proteinases and their inhibitors is important for extracellular matrix (ECM) degradation/remodelling at each stage of the metastatic cascade.

Expression of proteinases and inhibitors in human breast cancer progression and survival.

AIMS: The expression of proteinases and their inhibitors determines the extracellular matrix (ECM) turnover in normal and pathological processes. In cancer, proteolysis is abnormally regulated, favouring ECM degradation, which aids tumour invasion and metastasis. Previous studies have determined the expression of proteinases and inhibitors in breast cancer using a variety of techniques, including immunohistochemistry; however, most have looked at the expression of individual proteinases and/or inhibitors. Therefore, the aim of the current study was to determine the simultaneous cellular expression of matrix metalloproteinases (MMPs), plasminogen activators (PAs), and tissue inhibitors of metalloproteinases (TIMPs) in patients with breast cancer and correlate this with clinical pathological staging and survival. METHODS: Immunohistochemistry was used to determine the expression of proteinases (MMP-1, MMP-2, MMP-3, MMP-9, urokinase-type PA, and tissue-type PA) and inhibitors (TIMP-1 and TIMP-2) in 44 patients with breast cancer. RESULTS: The expression of all the factors studied was stronger or equivalent in tumour cells than in fibroblasts or inflammatory cells within the tumour section. Both positive and negative trends have emerged in the correlation between the cellular expression of proteinases and inhibitors and breast tumour pathology (tumour grade, lymphovascular invasion, and Nottingham prognostic index). CONCLUSIONS: The interactions between proteinases and their inhibitors in breast cancer progression are complex. Although there are differences in the expression of these factors that relate to differences in breast cancer pathology, there are no outstanding individual factors that consistently correlate with prognosis. Therefore, different factors are probably important at different stages of the process, and the balance in the relative concentrations of proteinases and inhibitors probably determines ECM degradation in breast tumour invasion and metastasis in vivo.

Measuring gelatinase activity in colorectal cancer.

AIMS: Gelatinases (MMP-2, -9) are the most extensively studied MMPs in cancer. The aim of the study was to determine the levels of active and latent forms of the gelatinases in paired colorectal tumour and normal tissue ( n=77) and correlate these with pathological stage. METHODS: Gelatinase levels were compared following the techniques of gelatin zymography (active and latent) and the novel gelatinase activity assays (total and endogenous/active). RESULTS: Both latent and active MMP-2 and MMP-9 lysis bands (zymography) and both total (active and latent) MMP-9 and endogenous (active) MMP-9 and MMP-2 levels (activity assays) were greater in tumour than normal colorectal tissue. Total MMP-2 and MMP-9 levels as determined by activity assays correlated with both the Dukes staging (e.g. total MMP-9 in tumours: adenoma, 1.0 (0.3--3.6); Dukes A, 9.6 (2.4--35.4); Dukes B, 14.7 (1.5--103.9); Dukes C, 22.3 (2.2--57.9) and Dukes D, 37.4 (2.1--47.0) ng/mg protein) and with lymphatic invasion (e.g. total MMP-9; in tumours which had undergone lymphatic invasion, 22.7 (2.1--57.9) and those with no lymphatic invasion, 14.0 (1.5--103.9) ng/mg protein). CONCLUSIONS: Both gelatinases were upregulated in tumour tissue, however total and not endogenous active levels correlated with the pathological stage of the tumour. Therefore gelatinases may only be activated when required for tumour invasion and metastasis.

Proteinases, their inhibitors, and cytokine profiles in acute wound fluid.

Wound healing is a complex process involving the interactions of many different cell types, matrix components and biological factors, including proteinases and cytokines. This study compared the levels of proteinases (matrix metalloproteinases and plasminogen activators), proteinase inhibitors (tissue inhibitors of metalloproteinases and plasminogen activator inhibitors), inflammatory cytokines and growth factors in acute wound fluid samples collected from the surgical drains of elective breast (n = 24) and colorectal (n = 26) patients on the first postoperative day. Gelatin zymography was used to determine matrix metalloproteinase-2 and -9 levels, quenched fluorescence substrate hydrolysis was applied for total MMP activity and enzyme-linked immunoassays were used to quantitate other factors. Colorectal wound fluid samples showed significantly (p < 0.05) greater levels of the matrix metalloproteinases (MMP-1, 2, 3, and 9), tissue inhibitor of metalloproteinases-1, urokinase plasminogen activator receptor and the inflammatory cytokines (interleukin-1beta, -6, and tumor necrosis factor-alpha); e.g., matrix metalloproteinase-3 colon; median 275 (range 11-2.530) ng/ml; breast; 530-400. However, tissue plasminogen activator and growth factor levels (epidermal growth factor, platelet-derived growth factor, basic fibroblast growth factor, transforming growth factor-beta1) were significantly greater in breast samples; e.g., epidermal growth factor breast 468 (103-1, 444) pg/ml; colon 57(1-573). There was no difference in the levels of urokinase type plasminogen activator, plasminogen activator inhibitor-1 and -2, tissue inhibitor of metalloproteinases -2 or vascular endothelial growth factor. Acute wound fluid from different surgical wounds showed different profiles of proteinases, proteinase inhibitors, and cytokines. This may lead to differences in the rate of tissue remodeling and therefore healing in these two wounds in vivo.

Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumour invasion and metastasis. The levels of MMPs, TIMPs and total MMP activity were compared in paired colorectal tumour (n = 50) and normal tissue (n = 49) samples and correlated with clinical and pathological staging. METHODS: Gelatin zymography (MMP-2 and MMP-9), enzyme-linked immunosorbent assays (MMP-1, MMP-3, TIMP-1 and TIMP-2) and quenched fluorescent substrate hydrolysis (total MMP activity) were employed in resection specimens from 50 patients, four with adenomas and 46 with colorectal cancer. RESULTS: The levels of active MMP-2 and MMP-9 and total MMP-1, MMP-3 and TIMP-1 were significantly greater in tumour tissue than in normal colon (e.g. TIMP-1 tumour median 72 (range 25-351) versus normal 26 (4-107) ng per mg total protein content; P<0.05); however, TIMP-2 levels were significantly greater in normal tissue (P<0.05). Total MMP activity was significantly greater in tumour than in normal tissue (15 025 (1750-174 400) versus 7250 (750-354 650) pmol l-1 min-1 mg protein-1; P<0.05). Correlations were found between both MMP and TIMP levels and pathological tumour staging. MMP-1 appeared to be most important as its concentration correlated positively with Dukes staging, tumour differentiation and lymphatic invasion. CONCLUSION: The levels of the studied MMPs and total MMP activity were upregulated in colorectal tumours. MMP-1 is important in colorectal cancer progression.

Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression.

AIMS: To plasminogen activator system (PAS) consists of the plasminogen activators (urokinase (uPA) and tissue-type (tPA) plasminogen activators), the uPA receptor (uPAR), and the plasminogen activator inhibitors (PAI-1 and PAI-2). Plasminogen activators activate plasminogen to plasmin, which can break down extracellular matrix (ECM) components. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is involved in angiogenesis. VEGF has been shown to upregulate uPA and this may facilitate tumour angiogenesis further. METHODS: PAS components and VEGF were determined by enzyme linked immunosorbent assay (ELISA) in paired colorectal tumour and normal tissue (n = 50) and correlated with pathological staging. RESULTS: uPA, uPAR, PAI-1, and VEGF values were significantly higher in tumour tissue (for example, tumour uPA: median, 2.3 (range, 0.1-6.7) ng/mg protein v normal uPA: median, 0.2 (range, 0-2.6) ng/mg protein). tPA was significantly higher in normal mucosa and there was no difference in PAI-2. uPA, uPAR, PAI-1, and VEGF values significantly correlated with each other and with Dukes's staging (uPA in adenomas: median, 0.42 (range, 0.1-1.2) ng/mg protein; upA in Dukes's B tumours: median, 2.1 (range, 0.4-4.3) ng/mg protein; and uPA in Dukes's D tumours: median, 4.0 (range, 3.7-4.2) ng/mg protein) and lymphatic invasion. In addition PAI-1 also correlated with tumour size and differentiation. CONCLUSION: The involvement of the PAS and VEGF in colorectal cancer appears to be complex. uPA, uPAR, PAI-1, and VEGF were upregulated in tumour tissue and this correlated with Dukes's staging and lymphatic invasion.

Medullary c-Fos activation in rats after ingestion of a satiating meal.

The distribution and chemical phenotypes of hindbrain neurons that are activated in rats after food ingestion were examined. Rats were anesthetized and perfused with fixative 30 min after the end of 1-h meals of an unrestricted or rationed amount of food, or after no meal. Brain sections were processed for localization of the immediate-early gene product c-Fos, a marker of stimulus-induced neural activation. Hindbrain c-Fos expression was low in rats that ate a rationed meal or no meal. Conversely, c-Fos was prominent in the medial nucleus of the solitary tract (NST) and area postrema in rats that ate to satiety. There was a significant positive correlation between postmortem weight of gastric contents and the proportion of NST catecholaminergic neurons expressing c-Fos. Cells in the ventrolateral medulla (VLM) were not activated in rats after food ingestion, in contrast with previous findings that stimulation of gastric vagal afferents with anorexigenic doses of cholecystokinin activates c-Fos expression in both NST and VLM catecholaminergic cells. These findings indicate that anatomically distinct subsets of hindbrain catecholaminergic neurons are activated in rats after food ingestion and that activation of these cells is quantitatively related to the magnitude of feeding-induced gastric distension.

Sustaining collaborative problem solving: strategies from a study in six Asian countries.

This paper presents findings from seven case studies of collaborative problem solving. The cases represent models of large-scale collaborative effort to improve the social, economic or health status of residents in poor communities. In these examples a variety of organizations worked together: government, business, voluntary agencies, community groups and people's organizations. A range of strategies was evident as these entities tried to sustain their collaboration. Strategies identified included those deployed collectively, those used by an individual organization to maintain its ability to participate and those used to persuade or pressure needed collaborators to become involved or stay the course. Specific strategies employed and descriptions of their use are presented and comprise a compelling profile of how collaborative problem solving functions.

Use of a laser-produced plasma as a source of focused vacuum-ultraviolet continuum radiation.

We report use of laser-generated plasmas as ultraviolet continuum sources of high shot-to-shot and long-term reproducibility suitable for photoelectric scanning measurements of absorption spectra. We have used such a source combined with a focusing geometry to obtain resonance-line-absorption profiles from a 30-cm column of hot plasma. This work also confirms and extends the photographic evidence of Carroll et al. that intense and line-free continua can be obtained from such plasmas with suitable choice of target material.