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re Anwendungskompetenz mus gestarkt werden. Technologiepolitik soll die Entstehung sowie die rasche Umsetzung und Verbreitung von neuem, technikrelevantem Wissen und Konnen zwecks wirtschaftlichem Erfolg am Markt unterstutzen. Damit liegt der Primat aufder Wirt¬ schaftspolitik; Technologiepolitik wird als technologie¬ orientierte Wirtschaftspolitik verstanden, in Abgren¬ zung zur Forschungs-, Wissenschaftsund Bildungs¬ politik.

Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation. HT-29 (human) and CC531 (rat) colon carcinoma cells were fluorescence labeled using CalceinAM. Single cell suspensions were injected intraarterially in Sprague-Dawley rats. Using intravital fluorescence microscopy adhesive interactions of circulating tumor cells within the hepatic microcirculation were observed at the liver surface. These interactions were analyzed regarding their time course and the localization within the vascular tree. Autofluorescence of liver parenchyma was sufficient for distinction of hepatic sinusoids. Intravital microscopy enabled the differentiation of early events in adhesion formation within hepatic sinosoids, adhesion stabilization, and extravasation of the tumor cells into the liver parenchyma. Tumor cell adhesion occurred almost exclusively within sinusoidal capillaries; however, the diameter of these vessels was usually larger than that of the tumor cells leaving remaining perfused lumen of the capillaries. Colon carcinoma cells rapidly migrated into the liver parenchyma after successful adhesion within the sinusoids. In contrast to common endpoint assays of the metastatic cascade, this in vivo model allows investigations of metastatic colon carcinoma cell adhesion within the liver microcirculation as specific steps during the formation of hematogenous metastasis and their underlying mechanisms.

Objective: To describe a weight-management clinic software system and to report on its preliminary evaluation. Research Methods and Procedures: The software system standardizes the collection of relevant patient information from an initial medical assessment, weekly clinic visits, and laboratory testing protocol of a medically supervised proprietary meal-replacement program in a university-based referral clinic. It then generates monthly patient feedback reports with graphs of clinical and laboratory parameters to support a patient-centered approach to weight management. After patients and clinic physicians review the data to ensure accuracy, the database is used for subsequent patient feedback reports, reports to referring physicians, quality assurance, and research. Clinic physicians and referring physicians were asked to rate their acceptance of the system. In addition, in a retrospective analysis of data generated by the system, outcomes for patients who received system-generated feedback (n = 620) were compared with those who participated in the program before the introduction of feedback (n = 130). Results: Clinic and referring physicians reported that they had high overall satisfaction with the software and that the system saved them time, and the latter group reported that it decreased laboratory use. Regarding patients, the feedback group had lower dropout rates in the latter half of the program, better rates of attendance, completion of laboratory tests, and weight loss after 8 weeks. Discussion: The software seems to facilitate the effectiveness of the treatment protocol for obesity and generates a high-quality database for patient care, clinic administration, quality assurance, and research purposes.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

Integrins are cell surface molecules that mediate cell adhesion, but are also important regulators of tumor cell interactions with their microenvironment, tumor cell survival and growth. In addition, the αvβ3-integrins appear to be critical for microvessel formation in tumor-induced neoangiogenesis. The present study is the first to investigate the effects of therapeutic αvβ3-integrin inhibition in a chemically induced tumor model that largely resembles human colon carcinomas. Tumor induction was performed in 47 male Sprague-Dawley rats using 1,2 dimethylhydrazin (21 mg/kg) twice a week. After 20 weeks of tumor induction, 100% of the animals developed adenocarcinomas with a median of 13.5 macroscopic tumor nodules (range 12–17), but no distant metastases. During further tumor induction for an additional 10 weeks, rats were treated three times/week with (a) 15 mg/kg RGDfV-peptide that can block vitronectin and fibronectin receptors; (b) an equimolar amount of an ineffective cyclic control peptide; or (c) with equimolar amounts of a linear RGDS-peptide. At the end of this treatment period, rats were sacrificed, and tumor load was quantified macroscopically and confirmed by histological examination. For investigation of the involvement of tumor-induced neoangiogenesis microvessel, density was determined using CD31-immunostaining. After 30 weeks, control animals (group B) had 5–18 tumors (median 14.5). If rats were treated with RGDfV-peptide (group A), the number of tumor nodules was significantly reduced (P < 0.005) to a median of seven macroscopic tumors (range 2–10 tumors), which also represented a significant reduction (P < 0.005) compared with prior to treatment. Application of noncylic RGDS-peptides (group C) did not affect the number of tumor nodules (median 18; range 10–30 tumors). The diameters of tumor nodules were comparable (3.2–6.1 mm) in animals of all groups. In addition, microvessel density was significantly (P < 0.05) reduced in tumors in group A compared to control rats. The major side effect in the treatment group was increased susceptibility to respiratory infections. Our results demonstrate that αvβ3-integrin-receptor inhibition appears to be a therapeutic strategy for colorectal cancer. In our therapeutic model, late onset of treatment with integrin-blocking peptides resulted in an inhibition of tumor growth and a reduced tumor load which appeared to be mediated, at least in part, by inhibition of neoangiogenesis.

This study examined the validity and reliability of decisional balance scales for exercise (i.e., pros and cons) in a large longitudinal population-based randomized sample of Canadian adults ages 18 to 65 years (N = 703). Assessments were taken over 3 time points with 6-month intervals between testing. Content, factorial, concurrent, and construct validity along with internal consistency and test-retest reliability were established for the decisional balance scales. The developed measures have utility for researchers and practitioners who test and apply the exercise decisional balance constructs of the Transtheoretical Model.

Background. The purpose of this study was to test the ability of the Transtheoretical Model (TTM) to predict exercise stage transition of individuals in a large, untreated-population-based, random sample of Canadian adults (18–65 years of age) over two consecutive time periods. Methods. Assessments of TTM's stage of exercise behavior change, self-efficacy, pros, cons, experiential processes, and behavioral processes were made at baseline (time 1), 6 months (time 2), and 1 year (time 3). Six hundred eighty-three men and women, identified through random-digit telephone dialing, completed all measures across the three time points. Within each time period (time 1–2; time 2–3) participants were categorized as having regressed (moved back at least on stage), remained (no stage change), or progressed (moved forward at least one stage). Baseline TTM constructs were analyzed for their ability to predict change transition across the two time periods. Results. Of 40 possible predictions (20 for each time period) 18 (45%) were supported. Conclusions. Overall, the findings demonstrate partial support for the internal validation of TTM in the exercise domain. Implications of the findings are discussed and future directions for researchers, practitioners, and program planners are provided.

Many quantitative analysis methods for myocardial perfusion studies require as a central step a comparison with a 'normal' or average density distribution map or reference image. It has been recognized, however, that the normal distribution can be affected by patient attributes, including sex and weight or body habitus, and by acquisition attributes, including the choice of tracer and the position of the patient during imaging. Some authors have proposed separate reference images for the sexes and the tracer. This approach fails if a large number of binary attributes have to be considered, since one would need 2" reference images for each attribute. The problem is compounded when continuous attributes (e.g. age and weight) are included, especially if the approach is to average separate homogeneous groups for each attribute. We propose to create case-specific reference images for the interpretation of myocardial perfusion studies by creating a model based on the influence of each attribute. From a non-homogeneous population of normal cases, or cases presumed to be normal on the basis of the Diamond and Forrester stratification, the effect of patient and study attributes on the density distribution in the stress image and the density differences between rest and stress images were computed. The effects are computed by multi-linear regression, to account for cross-correlation. Significance is assigned on the basis of a partial Fisher test. The data are myocardial perfusion images matched in 3D to a template by an elastic transformation. Even though there was some cross-correlation in the data, we were able to show independent effects of sex, position (prone or supine), age, weight, tracer combination and stress method (exercise, persantine and adenosine). Taken as a whole, the multi-linear regression demonstrated a significant effect in 72% of the pixels within the myocardial volume. In addition, the distribution predicted by the model was equivalent to average images from homogeneous matched groups. In conclusion, our approach makes it possible to produce case-specific reference images without the need for multiple homogeneous large groups to produce averages for each possible patient or study attribute.

Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug.Immunohistochemistry was used for peritoneal, ovarian and rectovaginal endometriotic lesions (n = 27) and endometrium (n = 13). Reverse transcription polymerase chain reaction was applied to tissue samples and primary cell cultures of endometriotic lesions (n = 9) and endometrium (n = 8).In endometriosis and endometrium E-cadherin, N-cadherin, Twist, Snail and Slug were expressed on protein and mRNA level. E-cadherin expression was strong in epithelial cells, but single E-cadherin-negative cells were frequently present in endometriosis. In endometriosis N-cadherin, Twist and Snail expression were upregulated in comparison with endometrium. The expression of E- and N-cadherin was inversely correlated, while that of N-cadherin and Twist was positively correlated.This study strongly suggests that EMT may be regulated differently in endometriosis and the endometrium. Future research should further elucidate the regulation of EMT in the endometrium and endometriosis.

The efficacy of physical activity with a healthful diet to reduce obesity is established; however, little is known about the translation of effective lifestyle strategies for obesity reduction in primary care settings.We assessed the effectiveness of a 2-year behaviorally based physical activity and diet program implemented entirely within clinical practices to reduce obesity. A total of 490 sedentary, obese adults were randomized to usual care (n = 241) or to the behavioral intervention (n = 249). The usual care group received advice from their physicians about lifestyle as a strategy for obesity reduction. The behavioral intervention included individual counseling from health educators to promote physical activity with a healthful diet. The primary outcome was change in waist circumference (WC).A total of 396 participants completed the trial (80.8%). A significant main effect was observed for WC change within the intervention compared with usual care (P.001) that was sustained at 24 months (mean [SE], -0.9 [0.4] vs 0.2 [0.4] cm; P = .05). Secondary analyses revealed significant main effects for change in WC in men (P = .009) and women (P = .02). In men, the mean (SE) reduction in WC at 24 months was greater with behavioral intervention compared with usual care (-1.6 [0.6] vs 0.1 [0.6] cm; P = .049). In women, the behavioral intervention was associated with differences in WC compared with usual care at 6 and 12 months (P ≤ .01) but not at 24 months (P = .10).Behavioral intervention in clinical settings is associated with modest reductions in WC during a 2-year study in obese patients. However, the effectiveness of the intervention is restricted to men.clinicaltrials.gov Identifier: NCT00665158.

Consuming a diet lower in total fat is important for the prevention of many chronic diseases. Individual and population-based programs targeting this behavior must be theoretically grounded and consider the context within which dietary behavior change may be attempted. To identify the factors differentiating stage of readiness to follow a low-fat diet, a sample ( N = 1216) of adults was surveyed using 4 different staging algorithms to assess stages of change and associated social-cognitive variables ( pros, cons, and temptation ). Approximately 75% of the sample occupied the Action/Maintenance stages for all staging algorithms. In general, pros increased and cons decreased with higher stage occupation. Temptation decreased from the early pre-action to the action stages for the different staging algorithms. When developing programs to decrease dietary-fat intake, social-cognitive variables associated with stage transition for behaviors related to consuming a low-fat diet may have relevance to researchers and clinicians.

Background Stages of change are related to dietary fat consumption. Few studies have examined stage occupation within the context of purchasing low-fat foods. Objective To determine the stage-prevalence of individuals for purchasing low-fat foods; identify the frequency of misclassification into action and maintenance (A/M) stages for purchasing for low-fat foods; and explain the demographic and cognitive-variable differences between pseudo (or false positive) A/M and true A/M individuals. Design Data were collected using a self-administered questionnaire among English-speaking adults (n=1,001) who were randomly sampled by mail. Statistical analyses performed Descriptive statistics were used to compare the characteristics of the stage groups. Groups were compared using χ 2 tests and Student t test. Results Of those who reported being in A/M stages, 32% were misclassified by the staging algorithm and were not true A/M low-fat food purchasers. Conclusions Individuals who are in A/M stages for buying low-fat foods still purchase high-fat foods. Stage misclassification may be a persistent problem in studies of dietary change using the Transtheoretical Model.

Purpose. To determine whether a stress management (SM) program could improve cessation rates when added to usual care (UC) among women attempting to quit smoking. Design. Randomized controlled trial conducted during a 12-month period. Setting. Smoking cessation clinics located within two tertiary care centers in Ottawa, Ontario. Subjects. A total of 332 women smokers 19 years or older who smoked 10 or more cigarettes per day were recruited via advertisements. Intervention. Either UC (physician advice and nicotine replacement therapy) or UC plus an eight-session group SM training program (coping skills development relevant to smoking-specific and generic stressors). Measures. Point prevalence abstinence 2 and 12 months after study intake. A secondary outcome of interest was change in perceived stress during the intervention period. Results. On an intent-to-treat basis, the addition of SM to UC had no incremental effect on 2-or 12-month abstinence rates. Abstinence rates at 2 months were 26.2% vs. 31.7% in the UC and SM groups, respectively (p = .59). At 12 months, the rates were 18.5% vs. 20.7% (p = .86). When quit rates were compared including only participants who demonstrated adequate adherence to the intervention protocol, there was a significant difference between the UC and SM groups at 2 months (34.9% vs. 48.7%; adjusted odds ratio, 1.88; 95% confidence interval, 1.04–3.42; p = .04) but not at 12 months (23.0% vs. 28.2%; adjusted odds ratio, 1.24; 95% confidence interval, .64–2.41; p = .53). There was a significant reduction in perceived stress from preintervention to postintervention; however, this decrease was not moderated by group assignment. Conclusion. The addition of SM in our setting neither increased abstinence rates nor reduced perceived stress over and above UC in women motivated to quit smoking. Poor attendance at the SM intervention undermined its effectiveness.

Apreviousstudydemonstratedthatsuraminreducestheproliferationofhumanpancreaticcancer cellsinvitroandalso reducesthesecretionoftheproangiogenickey factor VEGF. Thisstudy examinedtheeffectofsuraminontumorgrowth,metastasisandangiogenesisinvivoinanortho­ topicnudemousemodel. 1mm 3 fragmentsfrom3humanpancreaticcancercelllines(MIAPaCa-2,AsPC-1andCapan1) wereorthotopicallyimplantedinthepancreasofthenudemice.Volumeofprimarytumor,local infiltration,metastasisandmicrovasculardensity(MVD)weredeterminedatautopsy.Toassess theeffectofsuraminonangiogenesis,othertumorbearinganimalsweretreatedwithaspecific inhibitorofangiogenesis(TNP-470). Suraminatlowconcentrations(10mg/kg)hadnoinfluenceontumorgrowth,metastasisor angiogenesisinMIAPaCa-2tumors.Athighconcentrations(60mg/kg)Suraminreducedprimary tumorgrowthanddisseminationinall3pancreaticcarcinomas.SuramininhibitedtheMVD,but notasstrongasthespecificangiogenesisinhibitorTNP-470.

Objective: Vessel sprouting is a prerequisite for tumor growth. The aim of this study was to characterize the early vascularization of pancreatic cancer by intravital microscopy and to evaluate the effects of an angiogenesis inhibitor. Materials and methods: Donor tumors of the ductal pancreatic cancer cell line DSL-6A were implanted into a dorsal skin fold chamber of Lewis rats. The therapy group (n = 8) received TNP-470 and the controls (n = 8) a carrier solution. The animals were examined daily by intravital microscopy until day 7. Results: The number of newly formed tumor vessels in the therapy group on day 7 was 6.0, the vessel density 17.4/cm and the tumor size 0.79 qmm. In the control group the number of newly formed tumor vessels averaged 9.2, the vessel density 54.0/cm and the tumor size 1.43 qmm. Conclusion: The results show the effectiveness of an angiogenesis inhibitor in the early phase of tumor vascularization and the suitability of the dorsal skin fold chamber model for direct and continuous observation of tumor vascularization.

Objectives. To predict exercise stage transitions over two consecutive 6-month periods using the theory of planned behaviour (TPB). It was hypothesized that different social cognitive constructs would predict different stage transitions. Design. Prospective and longitudinal in order to predict multiple stage transitions over time. Assessments were made at baseline, 6 months and 1 year. Method. Participants were a randomly selected population-based sample of 683 adults who completed two telephone interviews (baseline and 6 months) that assessed exercise stage, intention, perceived behavioural control, attitude, subjective norm, and social support, and a mailed survey (1 year) that assessed exercise stage. Results. Progression from pre-contemplation was predicted by intention, attitude and subjective norm; progression/regression from contemplation was predicted by intention, perceived behavioural control, attitude, and social support; progression/regression from preparation was predicted by intention and attitude; and regression from action/maintenance was predicted by intention, attitude and social support. Conclusions. Different social cognitive constructs predicted different stage transitions, which indicates that exercise behaviour change may be represented by a series of stage transitions. Moreover, the TPB may be a useful model for highlighting the key social cognitive constructs that are important for exercise stage transitions.

Prostaglandins and prostaglandin-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis. COX (cyclooxygenase) is the key enzyme of prostaglandin synthesis. Whereas COX-1 produces prostaglandin mediators for physiological reactions, COX-2 is overexpressed in acute pancreatitis. The aim of this study was to investigate whether a selective COX-2 inhibitor alters prostaglandin production and attenuates systemic disease sequelae in severe acute pancreatitis in rats.Severe acute pancreatitis was induced in 36 rats by standardized intraductal infusion of bile salt and intravenous cerulein infusion. Six hours after acute pancreatitis induction, rats were randomized to receive either no COX inhibition (saline), nonselective COX inhibition by indomethacin (3 mg/kg, i.v.) or selective COX-2 inhibition by NS-398 (10 mg/kg, i.v.). Serum concentrations of prostaglandin E2 were measured before and after acute pancreatitis induction and 24 hrs after starting therapy. Routine cardiorespiratory and renal parameters were monitored to assess organ function.Animals treated with the selective COX-2 inhibitor had significantly lower prostaglandin E2 values (211 +/- 17 vs. 366 +/- 37 and 435 +/- 13 pg/mL), produced more urine (18 +/- 4 vs. 13 +/- 3 and 12 +/- 3 mL/6-24 h) and had significantly fewer episodes of respiratory distress (defined as a pO280 mmHg or pCO250 mmHg for15 min; 12 vs. 57 and 71%) during the observation period than animals without or with nonselective COX inhibition.Selective inhibition of COX-2 reduces prostaglandin E2 serum levels in this model of acute pancreatitis. This together with improved renal and respiratory function suggests an attenuation of the systemic response to pancreatic injury. COX-2 inhibition may be another step toward optimizing therapy in severe acute pancreatitis.

The authors present some of the work currently being conducted at CEA, CNRS, INRIA, ONERA, and CNES in the framework of the Autonomous Planetary Rover program (VAP). A system concept approach for the VAP application is first presented. Attention is then given to the VAP perception system: some results obtained with stereovision by a correlation algorithm on outdoor simulated Mars terrain scenes are shown. >

Suramin, a polysulfonated naphthylurea compound, inhibits the proliferation of several human tumors in vitro and in vivo. The mechanisms of Suramin action include the inhibition of growth factor binding, an antiangiogenic effect and the inhibition of various nuclear enzymes. This study evaluates the effect of Suramin on proliferation, viability, cell cycle and apoptosis of human pancreatic cancer cells in vitro and in vivo growth in a clinically relevant orthotopic nude mouse model of pancreatic cancer. Cell cycle analysis revealed a decreased S-phase and an increased G0/G1-phase after Suramin treatment in 4 cell lines (Capan-2, PANC-1, MIAPaCa-2, AsPC-1), whereas the percentage of Capan-1-cells in S-phase was increased. High concentrations of Suramin increased the apoptotic fraction in all 5 cell lines, Suramin inhibited the proliferation of pancreatic cancer cells in a dose-dependent manner and reduced viability at high concentrations. The mechanisms of in vitro action of this antiproliferative drug seem to involve alterations of cell cycle kinetics and apoptosis. In vivo treatment with Suramin significantly reduced pancreatic tumor size and metastatic spread in an orthotopic nude mouse model.

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

Zielsetzung: Das Pankreaskarzinom ist typischerweise ein szirrhoser Tumor, umgeben von einem chronisch entzundlich veranderten Randwall. Die damit assoziierte Gewebehypoxie ist moglicherweise ein Grund fur den aggressiven Phanotyp des Pankreaskarzinoms, da Hypoxie bei anderen Krebszellen zu einer erhohten Metastasierungsbereitschaft sowie zu einer Stimulierung der Neoangiogenese uber die Produktion proangiogener Faktoren wie Vascular Endothelial Growth Factor (VEGF) fuhrt. Diese Studie untersucht den Einflus von Hypoxie auf das humane Pankreaskarzinom in vitro und in vivo. Material und Methoden: Die humanen Pankreaskarzinom-Zellinien MIAPaCa-2 (MP; undifferenziert) und Capan-1 (Cl; gut differenziert) wurden fur 48 Stunden entweder hypoxischen (0% O2, 5% CO2) oder normoxischen Kulturbedingungen ausgesetzt. Danach wurde die Zellproliferation durch Zahlung in einem Hamozytometer und die Zellvitalitat durch den MTT-Assay gemessen. Die Verteilung der Zellzyklusphasen sowie die Apoptose wurden mittels FACS-Analyse bestimmt. Durch ELISA erfolgte die Bestimmung der VEGF-Konzentration im Zellkulturmedium. In vivo wurden 107 Zellen jeder Zellinie nach hypoxischer oder normoxischer Vorbehandlung entweder subkutan (sc.) oder in das Pankreas (orthotop; ot.) von Nacktmausen (n = jeweils 8) injiziert. Die Euthanasie der Tiere erfolgte nach 14 Wochen bzw. wenn klinisch eine massive Tumorlast (Bulky Disease, Kachexie, Aszites) vorlag. Dann wurde das Primartumorvolumen sowie lokale Infiltration und Metastasierung (Disseminierungsscore) erfast.

Blockade of the proangiogenic vascular endothelial growth factor (VEGF) and inhibition of matrix metalloproteinases (MMP) are promising novel treatment strategies for cancer. This study assessed the effects of a neutralizing anti-VEGF antibody (A4.6.1) and a MMP inhibitor (BB-94) on pancreatic cancer (PaCa) in vivo in an orthotopic nude mouse model. Monotherapy with either A4.6.1 and BB-94 significantly reduced tumor size, metastatic spread, and microvessel density in PaCa derived from two cell lines (HPAF-2, AsPC-1), thereby increasing survival. Combined VEGF blockade and MMP inhibition elicited additive effects in tumors derived from moderately differentiated HPAF-2 cells. This study adds further evidence for the therapeutic potential of antiangiogenic VEGF blockade and MMP inhibition in experimental PaCa.

Controversy still exists for therapy of inoperable colorectal liver metastases. Regional therapy has been considered a promising approach because several clinical studies demonstrated prolonged survival. The aim of this study was to investigate tumor targeting of the most frequently used cytostatic 5-fluouracil by modifying systemic and regional therapy by liposome encapsulation. Our results demonstrate that encapsulation of 5-FU in SUV-PEG liposomes increased tumor concentration by the factor 25 fold with systemic and factor 85 with regional therapy. Reduction of blood flow by starch microspheres (SMS) during regional chemotherapy with liposome-encapsuled 5-FU resulted in an additional 4000 fold increase in 5-FU tumor concentration.

Microcirculatory disorders (MCD) in severe acute pancreatitis (AP) are not confined to the pancreas but can also be found in other organs (e.g. colon, liver, lungs), where they contribute to AP-associated multiple organ dysfunction syndrome (MODS). Therapy aimed at enhancing microcirculation has been shown to ameliorate MODS even when therapy is delayed to a point at which pancreatic necrosis can no longer be influenced. Thus, research on novel methods for enhancing microcirculation is of particular interest in AP. The aim of this study was to evaluate the effect of a novel perfluorochemical oxygen carrier in AP and compare it with an established method for enhancing microcirculation, i.e. isovolemic hemodilution (HD). Six hours after induction of severe AP by intraductal bile salt infusion and i.v. cerulein, 18 rats were randomized into 3 groups (6 animals each) for therapy with [SAL]: 5 ml/kg normal saline i.v. (untreated controls); [HD]: isovolemic hemodilution by exchange of 8 ml/kg blood for hydroxyethylstarch, or [OXY]: 5 ml/kg perfluobron emulsion i.v. (3 g/kg Oxygent™, Alliance Pharmaceutical Corp. San Diego). At 24 hours intravital microscopic determination of pancreatic and colonic capillary blood flow (CBF). Additional monitoring included measurement of heart rate, arterial blood pressure and blood gases, hematocrit, and urine output. Hemodilution therapy significantly reduced hematocrit (33 ± 2 vs. 44 ± 2% in saline-treated controls) and improved CBF in the pancreas (1.8 ± 01 vs. 1.3 ± 0.1 nl/min) and colon (1.6 ± 0.1 vs. 1.3 ± 0.1 nl/min). This was associated with a stabilization of cardiorespiratory parameters (RRsys 112 ± 17 vs. 94 ± 8 mmHg; O2 saturation 95 ± 2 vs. 81 ± 9%). Therapy with Oxygent had comparable beneficial effects on microcirculation and cardiorespiratory parameters (pancreatic and colonic CBF 1.7 ± 0.1 nl/min; RRsys 115 ± 15 mmHg; O2 sat. 96 ± 2%) without reducing hematocrit (43 ± 2%). This suggests that perfluorochemical oxygen carriers may be an option for enhancing microcirculation and stabilizing organ function in severe acute pancreatitis. Further studies will evaluate whether they should be used instead of or in combination with hemodilution.

PURPOSE The purpose of this study was to investigate the factors associated with exercise behavior among adults with diabetes. METHODS Exercise behavior (stage of exercise readiness and energy expenditure) and potential determinants were measured on a subsample (n=46) of adults with type 1 or type 2 diabetes from a randomized population-based telephone survey. Participants were assessed at baseline and at a 6-month follow-up. RESULTS Sociodemographic and biomedical characteristics did not significantly differ between the stages of exercise behavior. Scores on the psychosocial constructs of self-efficacy, behavioral processes, self-concept, and social support were significantly higher for those in the action stage than those in the preaction stage of exercise readiness. Self-efficacy and behavioral process of change were significantly associated with energy expenditure; self-efficacy was the strongest predictor in the longitudinal analysis. CONCLUSIONS These findings may generate direction for theory development and guide health and medical practitioners when intervening on the specific constructs. Populationand community-based surveys have utility for assessing diabetes health-related behavior (eg, exercise behavior).

Prostaglandins (PG) and PG-derived mediators play an important role in mediating the systemic inflammatory response in acute pancreatitis (AP). Whereas COX-1 produces PG mediators for physiological reactions, COX-2 is overexpressed in AP. The present study investigates whether a selective COX-2 inhibitor alters PG production and attenuates systemic disease sequelae in severe AP in the rat. Six hours after induction of severe AP by intraductal bile salt infusion and i.v. cerulein, 36 rats were randomized for therapy with: [A] the selective COX-2 inhibitor NS-398 (10 mg/kg), [B] indomethacin (3 mg/kg) for non-selective COX inhibition, or [C] saline. Prostaglandin E2 (PGE-2) was measured using ELISA before and after AP induction and 24 h thereafter. Assessment of organ function included measurements of heart rate, blood pressure, blood gases and urine output at 0,6 and 24 h. At 24 h following AP induction, NS-398-treated animals had significantly lower serum levels of PGE-2 (211±17 pg/ml) than those treated with indomethacin (366±37) and saline (435±13). NS-398-treated animals produced more urine ([A], 18±4; [B], 12±3; [C], 13±3 ml/6 – 24 h) and had fewer episodes of respiratory distress ([A], 12%; [B], 57%; [C], 71% ) . It is suggested that selective COX-2 (rather than non-selective COX) inhibition attenuates the systemic inflammatory response to pancreatic injury and that this may be another step towards optimizing therapy in severe AP.

This study evaluated the role of the polyfunctional cytokine Endothelin-1 (ET-1) and its receptors A and B (ETRA, ETRB) in exocrine pancreatic cancer. Expression of mRNA for ET-1 was detected in all tested human cell lines (Capan-1, AsPC-1, MIAPaCa-2, PANC-1). All but one cell line (PANC-1) expressed mRNA for ETRA. None of the cell lines expressed ETRB mRNA. In vitro proliferation of ETRA positive cell lines was significantly reduced by selective ETRA blockade with LU-302146. Proliferation of ETRA negative PANC-1 cells was not influenced by LU-302146. In vivo, treatment with LU-302146 reduced primary tumors, metastasis, and ascites in an orthotopic nude mouse model of ETRA positive MIAPaCa-2 und AsPC-1 tumors, resulting in a tendency towards increased survival. ET-1 seems to modulate the proliferation of pancreatic cancer cells via ETRA. Selective ETRA blockade may provide a novel therapy option for ETRA-positive pancreatic cancers.

The goal of this study was to identify common sources of distress in spouses of patients undergoing cardiac rehabilitation and to compare spouses classified as being in distress and those classified as nondistressed on demographic variables, their experiences of stress, coping strategies employed, marital intimacy, and level of family functioning. The study aimed to describe the needs of spouses with respect to possible interventions.A cross-sectional analysis was used.The study was located at the University of Ottawa Heart Institute Prevention and Rehabilitation Centre's cardiac rehabilitation program.Scores on the Brief Symptom Inventory, Heart Disease Hassles Scale, Coping Strategies Inventory, Miller Intimacy Scale, and McMaster Family Assessment Device were used as outcome measures.Two hundred thirteen female spouses of patients undergoing cardiac rehabilitation participated in this study. Sixty-six percent of the spouses met the criteria for distress. This was more common in younger spouses (51.99 +/- 9.94 years) than in older spouses (55. 74 +/- 10.54 years) (t = -2.45; P =.013). Distressed spouses used disengagement coping strategies significantly more than the nondistressed spouses (t = 6.91; P =.0001). Distressed spouses also reported significantly less intimacy in their marriages (t = -3.99; P =.0001) and poorer family functioning (t = 5.86; P =.0001). The most prevalent symptoms of psychologic distress included feeling tense, having trouble falling asleep and feeling easily hurt. The most prevalent stressors were as follows: (1) worries about treatment, recovery, and prognosis (75.5%); (2) moodiness of the patient (66.7%); (3) worries about the patient returning to work and about money (38.8%); (4) sexual concerns (36.7%); and (5) helplessness or apathy on the part of the patient and increased spousal responsibility (36.1%).Spouses of patients undergoing cardiac rehabilitation should be screened for psychologic distress, and those in distress should be offered interventions focused on assisting them to deal with specific stressors related to their experience with a spouse with heart disease. Interventions indicated include stress-management techniques and encouraging the use of engagement coping strategies. In addition, marital and family concerns need to be directly addressed in support interventions.

A new approach to mission operations will be flight validated on NASA’s New Millennium Program Deep Space One (DS1) mission which launched in October 1998. The Beacon Monitor Operations Technology is aimed at decreasing the total volume of downlinked engineering telemetry by reducing the frequency of downlink and the volume of data received per pass. Cost savings are achieved by reducing the amount of routine telemetry processing and analysis performed by ground staff. The technology is required for upcoming NASA missions to Pluto, Europa, and possibly some other missions. With beacon monitoring, the spacecraft will assess its own health and will transmit one of four beacon messages each representing a unique frequency tone to inform the ground how urgent it is to track the spacecraft for telemetry. If all conditions are nominal, the tone provides periodic assurance to ground personnel that the mission is proceeding as planned without having to receive and analyze downlinked telemetry. If there is a problem, the tone will indicate that tracking is required and the resulting telemetry will contain a concise summary of what has occurred since the last telemetry pass. The primary components of the technology are a tone monitoring technology, Al-based software for onboard engineering data summarization, and a ground response system. In addition, there is a ground visualization system for telemetry summaries. This paper includes a description of the Beacon monitor concept, the trade-offs with adapting that concept as a technology experiment, the current state of the resulting implementation on DS1, and our lessons learned during the initial checkout phase of the mission. Applicability to future missions is also included.

Many of the complications of severe acute pancreatitis are the result of the amplifying effects of microcirculatory disruption. The factors causing microcirculatory disorders in acute pancreatitis involve vasoactive mediators such as platelet-activating factor (PAF) and endothelin-1 (ET) activated during the inflammatory response to pancreatic injury. To further evaluate the potential therapeutic role of specific receptor antagonists (RA) to these mediators, the present study compares the effect of PAF and ET receptor blockade on microcirculation and organ function in a well-established rodent model of severe acute pancreatitis. Six hours after acute pancreatitis induction, rats were randomized to therapy with ET-RA (50 mg/kg LU-135252), PAF-RA (82 microg/kg WEB-2170), or NaCl 0.9% (volume equivalent). After 18 hours of fluid resuscitation, animals were relaparotomized for intravital microscopic determination of capillary blood flow, leukocyte rolling, and capillary permeability in the pancreas and colon. Other measurements included cardiorespiratory parameters, hematocrit, pleural effusions, ascites, urine production, and survival. Compared to saline treatment both ET-RA and PAF-RA significantly improved capillary blood flow in the pancreas and colon, reduced leukocyte rolling, and stabilized capillary permeability. The beneficial effects of receptor antagonist treatment on microcirculation were associated with decreased fluid loss into the third space, improved renal and respiratory function, and survival. Although both receptor antagonists likewise improved capillary blood flow, ET-RA was significantly more effective in counteracting leukocyte rolling and capillary leakage, thereby further reducing fluid sequestration. The present study confirms the beneficial effects of PAf and ET receptor blockade on microcirculation inside and outside the pancreas, organ function, and survival when given at the early stage of severe pancreatitis. Because ET-RA was more effective in stabilizing capillary permeability and avoiding subsequent fluid loss into the third space, we propose that ET-RA should be tested in a clinical trial (either in comparison or in addition to PAF-RA).

Despite being central to Canadian health objectives, reduction in fat consumption remains a difficult health target to reach. Strong epidemiological data associate high dietary fat intake with cardiovascular disease (CVD). There has been considerable interest in applying concepts from psychosocial models of behaviour change to enhance the effectiveness of CVD prevention programs. This review suggests that the determinants of fat-related dietary behaviours can be integrated within a comprehensive model useful to public health practice. The Transtheoretical Model (TTM) is suggested as an organizing framework for variables empirically related to diet. The TTM holds that dietary change occurs through successive stages, defined according to people's readiness to adopt new behaviours. Furthermore, readiness to change can be explained by variables that are amenable to public health interventions. The integration of important variables within the TTM framework may prove helpful in designing, implementing and evaluating effective dietary change intervention programs in the community.

This brief paper presents an integrative framework helpful in understanding the relationships between stress and cardiovascular disease risk behaviours. Key concepts such as cardiovascular reactivity, type A behaviour and hostility, ways of coping with both life and illness-related stressors, and the challenges associated with changing risk behaviours can support a patient's behaviour change efforts if communicated in a personally salient manner. Assessing the determinants of health behaviour change facilitates tailoring of interventions and can more precisely identify a patient's needs for referral to a psychologist with expertise in health behaviour issues.

Self-efficacy is an important mediator of behaviour change. We have developed a brief measure of self-efficacy related to ability to make dietary changes to lower serum cholesterol. An initial pool of 37 items was tested on 85 third-year nursing students. Factor analysis revealed two primary factors ('self-efficacy for resistance to temptation' and 'self-efficacy for change') composed of 13 items. This instrument was validated in a sample of 125 blue collar workers. Analyses confirmed that the scale structure accounted for 37% of the variance. Evidence of discriminant validity was provided by moderate correlations between factors (r = 0.41). Item-scale correlations also supported the discriminant validity. Cronbach's alpha ranged between 0.7 and 0.79 for both factors. This short instrument might be useful as an adjunct tool to identify potential responders for cholesterol modification interventions, to help understand the determinants of dietary behaviour changes and to guide the tailoring of interventions toward specific client/population subgroup needs.

International audience; This paper describes the development and implementation of a reactive visual module utilized on an autonomous mobile robot to automatically correct its trajectory. We use a multisensorial mechanism based on inertial and visual cues. We report here only on the implementation and the experimentation of this module, whereas the main theoretical aspects have been developed elsewhere.