Impact of "early intervention" parent workshops on outcomes for caregivers of children with neurodisabilities: a mixed-methods study.

PURPOSE: This study explored the feasibility, impact and parent experiences of ENVISAGE (ENabling VISions And Growing Expectations)-Families, a parent-researcher co-designed and co-led program for parents/caregivers raising children with early-onset neurodisabilities. METHODS: Parents/caregivers of a child with a neurodisability aged ≤6 years, recruited in Australia and Canada, participated in five weekly online workshops with other parents. Self-report measures were collected at baseline, immediately after, and 3 months post-ENVISAGE-Families; interviews were done following program completion. Quantitative data were analyzed with generalized estimating equations and qualitative data using interpretive description methodology. RESULTS: Sixty-five parents (86% mothers) were recruited and 60 (92%) completed the program. Strong evidence was found of effects on family empowerment and parent confidence (all p ≤ 0.05 after the program and maintained at 3-month follow-up). The ENVISAGE-Families program was relevant to parents' needs for: information, connection, support, wellbeing, and preparing for the future. Participants experienced opportunities to reflect on and/or validate their perspectives of disability and development, and how these perspectives related to themselves, their children and family, and their service providers. CONCLUSIONS: ENVISAGE was feasible and acceptable for parent/caregivers. The program inspired parents to think, feel and do things differently with their child, family and the people who work with them.Implications for rehabilitationENVISAGE (ENabling VISions And Growing Expectations)-Families is a co-designed, validated parent/researcher "early intervention and orientation" program for caregivers raising a child with neurodevelopmental disabilities (NDDs).ENVISAGE-Families empowered parents' strengths-based approaches to their child, family, disability, and parenting.ENVISAGE-Families increased caregivers' confidence in parenting children with NDD's and provided them tools to support connection, collaboration, and wellbeing.Raising children with NDD can have a profound impact on caregivers, who can benefit from strengths-based, future focused supports early in their parenting experience.

Improving aeration control at the Ljubljana wastewater treatment plant.

This paper describes an improvement to the aeration control at the Ljubljana wastewater treatment plant. Several changes were made to the existing aeration control. An adjustment to the parameters of the common air pressure controller contributes to a more responsive operation of the compressors. The introduction of the air pressure set-point controller adjusts the air pressure in the common air rail according to the changes in the plant load. The introduction of the airflow controllers reduces the variation in the oxygen concentrations in the aerobic reactors and, consequently, enables a reduction in the oxygen set-points. With the improved aeration control, savings of up to 10% in the electricity used for aeration are achieved on a yearly basis.

Functionalization of biodegradable magnesium alloy implants with alkylphosphonate self-assembled films.

Mg and Mg-alloys are promising materials for biodegradable implants. In order to slowdown the Mg-alloy (AZ91D) degradation and enhance its biocompatibility, the alloy surface was modified with alkylphosphonate self-assembling films. The binding configuration and the structural organization of alkylphosphonate monolayers on the Mg-alloy surface were investigated using contact angle measurements, FTIR, and XPS. Combination of FTIR and XPS data indicated the presence of several different bonding modes (mono-, di-, and tri dentate) of phosphonate head groups with the alloy surface. The existence of well organized and ordered self-assembled alkylphosphonate monolayers with good barrier protecting properties in a physiological solution is a key step in the development of biocompatible Mg-alloy implants.

Ventricular and vascular remodelling effects of the angiotensin II receptor blocker telmisartan and/or the angiotensin-converting enzyme inhibitor ramipril in hypertensive patients.

Angiotensin II induces inflammatory activation of vascular smooth muscle cells and can cause left ventricular hypertrophy (LVH). Telmisartan is an angiotensin II receptor blocker with demonstrated beneficial effects on cardiac and vascular structure and function in animal models. The angiotensin-converting enzyme inhibitor ramipril also reduces ventricular and vascular remodelling. The open-label study observed 75 treatment-naive, moderately or severely hypertensive (systolic blood pressure 160-190 mmHg, diastolic blood pressure 90-110 mmHg) patients (age range, 42-58 years) treated with once-daily telmisartan 40 mg force-titrated to 80 mg after 1 month (n=25), once-daily ramipril 2.5 mg force-titrated to 5 mg after 1 month (n=25), or once-daily telmisartan 40 mg plus ramipril 2.5 mg (n=25); the total duration of treatment was 6 months. At baseline, blood pressure, left ventricular mass index (LVMI), carotid intima-media thickness (IMT) and carotid cross-sectional intima-media area (CSA) were measured. Measurements were repeated 1, 3 and 6 months after initiation of treatment. After 6 months, comparable blood pressure reductions were achieved with the three treatments. Reductions in LVMI after 6 months' treatment were 11.4%, 9.9% and 15.6% with telmisartan, ramipril, and telmisartan plus ramipril, respectively. Respective reductions in IMT were 14.6%, 12.0% and 18.2%, and for CSA were 7.8%, 4.3% and 11.5%. In conclusion, treatment with telmisartan or ramipril for 6 months resulted in regression of LVH and vascular remodelling. When a combination of telmisartan and ramipril was administered, additional regression and remodelling occurred.

Endometrial stromal sarcoma arising in extrauterine endometriosis: a case report.

We report a rare case of a 46-year-old woman developing endometrial stromal sarcoma (ESS) on the grounds of extrauterine endometriosis. The patient presented with symptoms of stenosis of the rectosygmoid colon. The tissue samples were submitted to histological and immunohistochemical analyses using antibodies for indirect staining. The trial showed multiple foci of endometriosis and mesenchymal malignant tissue described as ESS in the bowel wall, mesentery and in the remnants of the left adnexae. According to our findings, we suspect that ESS might have arisen in colon endometriosis.

Primary non-Hodgkin lymphoma of the humerus following traumatic injury: case report.

A case of primary non-Hodgkin lymphoma of the right humerus which occurred in a 21-year-old male patient after an impact to the right shoulder in a car accident in July 1983 is described. Seventeen years after the injury, due to a civil lawsuit, the biopsy material was revised. Immunohistochemical analysis showed CD20 and CD79a positivity on large pleomorphic cells, while small reactive lymphocytes were CD3, Bcl-2 and CD20 positive. Molecular analysis carried out with PCR revealed a monoclonal B-lymphocyte population. The diagnosis of diffuse large peripheral B cell lymphoma of the bone was confirmed. The present case concurs with the literature on primary bone lymphoma, in which the diagnostic problem, trauma-related presentation and an excellent prognosis of malignant tumour are emphasized.

Death due to accidentally self-inflicted gunshot wound.

A 37-year-old man, with the entrance gunshot wound on the front of the right leg several cm above the knee, was found dead at home in his bed. No other lesions were observed except a contusion ring around the wound that spread downward and to the right. On autopsy, the wound path was followed upward from the entrance wound (0.7 cm in diameter). The bullet went through the medial aspect of the quadriceps and adductor muscles and continued upward, adjacently to the internal iliac artery, perforating the pelvic floor and the median lobe of the prostate. It passed by the left kidney, injuring its fatty capsule, then went through the mesentery near the left segment of the transverse and descending colon, and entered the thoracic cavity through the diaphragm, injuring the posterior wall of the pericardium and the posterior wall of the left ventricle at the level of the first left rib. The bullet was found in the apex of the left lung. Death was caused by cardiac tamponade.

Single-day loading dose of oral amiodarone for the prevention of new-onset atrial fibrillation after coronary artery bypass surgery.

BACKGROUND: Various regimens have been proposed for the prevention of postoperative atrial fibrillation, including the use of intravenous and oral amiodarone. The purpose of this study was to determine the effectiveness of a single-day loading dose of oral amiodarone in prophylaxis of atrial fibrillation during the 7 days after coronary artery bypass surgery. METHODS: We conducted a double-blind, randomized, placebo-controlled study encompassing 315 consecutive patients who underwent coronary artery bypass surgery. They received either amiodarone (159 patients) or placebo (156 patients). Therapy consisted of a single oral loading dose of 1200 mg of amiodarone 1 day before surgery, followed by the maintenance dose of 200 mg daily during the next 7 days. Only episodes of atrial fibrillation lasting more than 1 hour or associated with hemodynamic compromise were taken into consideration. RESULTS: Overall, the incidence of atrial fibrillation was similar in patients who received amiodarone (31/159, 19.5%) and placebo (33/156, 21.2%) (P = .78). However, amiodarone reduced the incidence of atrial fibrillation in elderly patients (age > or = 60 years): it occurred in 20 of 75 (26.7%) patients on amiodarone and in 28 of 65 (43.1%) patients in the placebo group (P = .05). There were no differences between the study groups regarding the postoperative intrahospital morbidity and mortality and the duration of hospital stay. CONCLUSIONS: A single-day loading dose of oral amiodarone (1200 mg) does not prevent postoperative atrial fibrillation in a general population of patients undergoing coronary artery bypass surgery. However, it appears that this regimen reduces the occurrence of postoperative atrial fibrillation in elderly patients.

Dipyridamole-atropine-induced myocardial infarction in a patient with patent epicardial coronary arteries.

BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.

c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems.

PURPOSE: The c-erbB-2 gene (encoding the protein p185) is overexpressed in diverse human cancers and has been implicated to be of prognostic value in gastric cancer. Recent studies suggest a role of p185 in tumor progression by specifically promoting the invasive capacity of tumor cells. Therefore, the present study was conducted with the following three objectives: (1) to support the prognostic value of c-erbB-2 in gastric cancer in a large prospective series using a monoclonal antibody and a highly sensitive immunohistochemical method; (2) to determine the association of c-erbB-2 expression with the expression of invasion-related genes; and (3) to perform the first overall multivariate analysis including c-erbB-2 and the invasion-related tumor-associated protease systems. PATIENTS AND METHODS: In a consecutive prospective series of 203 gastric cancer patients (median follow-up, 42 months), expression of c-erbB-2 and a panel of tumor-associated proteases and inhibitors by tumor cells were evaluated semiquantitatively (score 0 to 3) and analyzed for correlation (chi(2) test, Bonferroni-corrected). Kaplan-Meier survival analysis and multivariate Cox analysis were performed to determine the relative prognostic impact of c-erbB-2 and the invasion-related parameters. RESULTS: Kaplan-Meier analysis (log-rank statistics) revealed a significant association of increasing expression of c-erbB-2 with shorter disease-free (P =. 0023) and overall survival (P =.0160). High amounts of p185 were significantly associated with a high expression of urokinase-type plasminogen activator (uPA) (P <.010), uPA-receptor (P =.030), type-1 plasminogen activator inhibitor (PAI) (P <.010), type-2 PAI (P =.021), cathepsin D (P =.036), matrix metalloproteinase-2 (P =. 024), alpha-1-antichymotrypsin (P =.025), and alpha-2-macroglobulin (P =.017). Multivariate analysis considering these proteases/protease inhibitors, in addition to alpha-1-antitrypsin, tissue plasminogen activator, plasminogen, alpha-2-antiplasmin, and antithrombin III, and established prognostic parameters revealed that, in addition to surgical curability, pT stage, pN stage, and PAI-1, c-erbB-2 is an independent prognostic factor for overall survival of curatively resected patients (n = 139; P =.049; relative risk, 1.54; 95% confidence interval, 1.08 to 1.67) and all patients (P =.028; relative risk 1.33; 95% CI, 1.28 to 1.38). CONCLUSION: c-erbB-2 is confirmed as a new independent, functional prognostic parameter for overall survival in gastric cancer, even when a panel of invasion-related factors, including the strong prognostic parameter PAI-1, are considered. The significant correlation of p185 with several tumor-associated proteases supports the hypothesis that c-erbB-2 is a promoter of invasion and metastasis. This strongly suggests that c-erbB-2 may be a promising target for anti-invasive therapy in gastric cancer.

Prognostic significance of DNA ploidy pattern and nucleolar organizer regions (AgNOR) in colorectal carcinoma.

AIM: To investigate the prognostic significance of DNA ploidy and silver stained nucleolar organizer regions (AgNOR), as well as their relation to the histological grade and Dukes' stages of colorectal carcinomas, and the relation of tumor cells proportion in the S-phase and Dukes' stage, histologic grade, DNA ploidy, or AgNOR count. METHODS: DNA flow cytometric analysis and AgNOR were performed on 94 surgically removed colorectal carcinomas. The mean AgNOR count was calculated in 200 tumor cells for each case. Survival rates and tests for significance were evaluated using the log-rank test and Cox regression model. RESULTS: There were no significant correlations between the ploidy pattern, histological grade, and Dukes' stage. Diploid tumors had a significantly lower AgNOR count (median 2.5, range 2.1-7.7) than aneuploid (median 6.2, range 2.0-7.9). Dukes' C stage tumors exhibited higher AgNOR count than Dukes' A or B stages. The proportion of tumor cells in S-phase did not correlate with any other parameter. Each of these parameters failed to show any correlation with survival. After dividing the tumors into those with high (>5) and low AgNOR count (<5), no correlation was found in the latter group between AgNOR and any other studied parameters, whereas in the group with high AgNOR count correlations to Dukes' stage, DNA ploidy, and histological grade were established.Conclusions. The difference in survival between well, moderately, and poorly differentiated tumors were significant in the group with high AgNOR counts. Dukes' C stage and aneuploid tumors had the worst prognosis.

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology.

OBJECTIVES: The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND: Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS: Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

Comparison of microvessel density with tumor associated macrophages in invasive breast carcinoma.

Neovascularization, the growth and formation of capillary blood vessels, is an essential component of solid tumor growth and a critical step in metastasis. Tumor associated macrophages (TAMs) have several functions related to tumor biology including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define the TAM and microvessel density (MD) in human invasive breast carcinoma NOS and to correlate their values with lymph node status, tumor size, tumor grade and mitotic activity index (MAI), and, finally, to determine whether MD is connected with TAMs. A total number of 57 invasive breast carcinomas NOS were processed for immunohistochemical analysis using mAb to F-VIII to visualize endothelial cells and mAb to CD68 antigens for macrophages. Statistical analysis showed only a positive correlation between TAMs and MAI (p = 0.004). These results support the notion that intensity of tumor angiogenesis does not provide additional prognostic significance, while TAMs may play a positive role in breast cancer micro system since they regulate tumor proliferation.

Expression of monocyte chemotactic protein-1 in human invasive ductal breast cancer.

Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage infiltration of tumor tissue. Tumor associated macrophages (TAMs) are a population of mononuclear-phagocytic cells, which can express complex functions related to tumor biology. The present study was designed to analyse the expression of MCP-1 in parenchymal and stromal elements on frozen sections of 27 breast invasive ductal carcinomas not otherwise specified (NOS) by immunohistochemistry. The expression of MCP-1 in tumor parenchyma and the degree of tumor differentiation were assessed. MCP-1 was detected in the parenchyma in 15 of 27 ductal carcinomas. Positive immunoreactivity manifested as diffuse, homogeneous, moderate or strong, cytoplasmic staining, confined to tumor epithelium. Generally, MCP-1-negative tumors tended to be well differentiated, while chemokine-positive tumors exhibited a low level of differentiation. MCP-1 immunoreactivity was also present in TAMs (CD68 positive cells) in 23 of 27 tumors, and in endothelial cells in 11 of 27 tumors. These results indicate that parenchymal and, more variably, stromal elements of human invasive ductal carcinomas NOS can express MCP-1 in vivo. Additionally, these findings suggest that MCP-1 expression in tumor parenchyma is correlated with the histological grade of ductal invasive breast carcinoma.

Prognostic relevance of MMP-2 (72-kD collagenase IV) in gastric cancer.

The association of MMP-2 (matrix metalloproteinase 2, 72-kD collagenase IV) with invasive and metastatic capacity of tumor cells has implicated a potential role in the prognosis for cancer patients. However, no larger study has been done to prove this hypothesis. The present study was therefore designed to investigate the prognostic impact of MMP-2 in a prospective series of 203 gastric cancer patients. MMP-2 expression was measured immunohistochemically and scored semiquantitatively (score 0-3) in carcinoma cells, and results were correlated with clinicopathological tumor parameters and parameters of the urokinase-type plasminogen activator (uPA) system. Survival analyses were done using the Kaplan-Meier method (log-rank statistics) and multivariate Cox analysis. Significant correlations were found for MMP-2 and Laurén's classification, M stage and proteases/inhibitors of the uPA system in the primary tumor. Kaplan-Meier analysis revealed an association of increasing MMP-2 expression with worse prognosis. This was especially seen in patients with a parallel high expression of uPA receptor. However, differences in survival probabilities between low and high MMP-2 levels were not significant. In a separate analysis of diffuse-type cancers, MMP-2 was significantly associated with disease-free (p = 0.0056) and overall survival (p = 0.0426). Multivariately, MMP-2 was not an independent parameter. Our results demonstrate that there is an association of immunohistochemical detection of MMP-2 with prognosis of cancer patients. For diffuse gastric cancers, it is a significant prognostic parameter, however, not of independent impact. The study further suggests that consideration of interrelated tumor-associated proteases like uPA receptor in combination with MMP-2 may improve its prognostic power.

Tumor-associated proteases and inhibitors in gastric cancer: analysis of prognostic impact and individual risk protease patterns.

Expression of proteolytic parameters of the urokinase-type plasminogen activator (uPA) system [uPA receptor (uPA-R), plasminogen activator inhibitor (PAI)-1] has been proven to be an independent prognostic parameter in cancer. However, it has not been considered that the uPA system is interacting with several other protease/inhibitor systems, neither has a comparable prognostic role of these factors been investigated. Moreover, studies evaluating specific protease patterns indicating high individual risk are missing completely. Therefore, in a consecutive prospective series of 203 gastric cancer patients, the expression of activators (plasminogen, tPA, MMP-2, cathepsin D, antithrombin 3) and inhibitors (alpha-2-antiplasmin, alpha-2-macroglobulin, alpha-1-antitrypsin, alpha-1-antichymotrypsin) of proteolysis was studied immunohistochemically in the tumor epithelium semiquantitatively (score 0-3) in addition to the uPA system. Kaplan-Meier analysis (median time of follow-up 31 months) revealed a significant association of cathepsin D (P=0.0042), alpha-2-macroglobulin (P=0.0281) and antitrypsin (P=0.0372) with disease-free survival and of cathepsin D (P=0.0018), antitrypsin (P=0.0112) and antichymotrypsin (P=0.0002) with overall survival. Multivariate Cox analysis performed to correct these results for relative impact of the uPA system and established prognostic factors showed PAI-1 (disease-free survival: P=0.002, relative risk 1.86; overall survival: P=0.005, relative risk 1.39), pT and pN as independent parameters. Cathepsin D was shown to have an independent impact on disease-free survival (P=0.020, relative risk 2.98). Comparative chi-square analysis of cases with poor and good prognoses revealed that in patients with good clinical outcome, inhibitors of proteolysis are correlated significantly, whereas in patients with poor prognosis activators of proteolysis are significantly associated preferentially and significant correlations with the uPA-R are dominant. For detailed pattern analysis, stepwise overall Kaplan-Meier analyses were performed in subgroups of high uPA-R-, uPA-, PAI1- and cathepsin D expression for two additional proteases each. From these analyses, the combination of high (score 2/3) expression of uPA-R, PAI-1, antichymotrypsin and alpha-2-macroglobulin was identified as a high-risk pattern, representing parameters known to be essential for uPA-R internalization and recycling. This suggests some of the uPA-associated proteases and inhibitors investigated as univariate prognostic parameters in gastric cancer. Cathepsin D is a new independent parameter for disease-free survival. The study further demonstrates that a protease pattern promoting uPA-R recycling in tumor cells especially indicates high individual risk tumors in gastric cancer.

Automatic segmentation of intravascular ultrasound images: a texture-based approach.

Extraction of blood vessel boundaries from intravascular ultrasound images is essential in the quantitative analysis of cardiovascular functions. In this study, we are presenting a completely automated procedure for determining blood vessel borders. This approach uses textural operators to separate different tissue regions and morphological processing to refine extracted contours. The method was tested in a set of 29 intravascular ultrasound images obtained in vivo. To assess the performance of the method, we have compared the automatically processed images with the manual tracings, using three different criteria: correlation coefficient, match ratio, and relative error of computed shape parameters. In both contour detection and shape parameters estimation, the proposed method yielded consistently good results. Due to its robustness and accuracy, this approach is appropriate for clinical use, whereas computational efficiency of the method facilitates low-cost implementation.

Clinical value of extended biologic staging by bone marrow micrometastases and tumor-associated proteases in gastric cancer.

OBJECTIVE: To investigate whether extended staging, including biologic grading and aspects of an early systemic disease component, would give additional prognostic information on patients with curatively resected gastric cancer. BACKGROUND: Tumor-associated proteolytic mechanisms have been shown to be essential for invasion and metastasis. The urokinase-type plasminogen activator (uPA) system is of major biologic impact, but different interactive proteases and inhibitors with modulating effects also must be considered. The detection of early tumor cell dissemination indicates the systemic character of a primarily local gastric cancer. The confrontation of the organism with these cells determines the often unpredictable course of an individual tumor after presumed curative primary treatment. METHODS: In a prospective study of 247 consecutive patients with gastric cancer, detection of disseminated tumor cells in bone marrow aspirates was immunocytochemically performed in 180 patients. The expression of uPA, activators of uPA (cathepsin D, antithrombin III), uPA substrates (plasminogen, matrix-metalloproteinase 2 [collagenase IV, 72 kD; MMP-2]), uPA/plasmin inhibitors (plasminogen activator inhibitor type 1 and 2 [PAI-1, PAI-2], alpha1-antitrypsin, alpha2-antiplasmin), uPA receptor (uPA-R), and parameters of the uPA-R cycle (alpha2-macroglobulin, alpha1-antichymotrypsin) could be determined immunohistochemically and were scored semiquantitatively in 203 patients. Kaplan-Meier statistical techniques and multivariate Cox regression models were used for prognostic analyses. RESULTS: In multivariate analysis considering all the established risk factors, disease-free survival was independently predicted by PAI-1 (relative risk 2.21, 1.32-3.73) and cathepsin D (relative risk 2.98, 1.28-6.91) besides pT, pN, and extended resection. Tumor cell dissemination was found to be an additional prognostic factor in early tumor stages (pT1, T2) and lymphnode-negative patients. Stepwise regression analysis revealed an extended staging system with new risk groups. Node-positive, curatively resected pT1/2 patients with low expression of PAI-1 had a favorable prognosis (mean recurrence-free survival [MRT] 54.84 months), similar to that of node-negative patients (MRT 54.76 months). In node-negative, curatively resected pT1/2 patients, detection of bone marrow tumor cells and high expression of PAI-1 defined a subgroup with a steep decrease of prognosis (MRT 36.60 months), which was worse than that of node-positive patients (MRT 45.81). CONCLUSION: This new staging model gives better prognostic differentiation of subgroups, which should be considered in future adjuvant therapy protocols. In addition, it indicates that the uPA system might be a future therapeutic target.

Coronary vasodilation without myocardial erection. Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion.

AIM: The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P = ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P < 0.05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3% vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both tests, left ventricular end-diastolic pressure significantly increased (P < 0.05) in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/- 4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to < 50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant 'erectile' and adverse effects of coronary vasodilation per se.