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Kurt Ulm

Publications and source records attributed to Kurt Ulm.

28 records · Page 2Linked to original sources
PubMed2003

Pooled analysis of prognostic impact of uPA and PAI-1 in breast cancer patients.

In this report we present an extension of the pooled analysis of the prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I in breast cancer patients. We analyzed a different endpoint, metastasis-free survival (MFS). We checked the consistency of the estimates for uPA and PAI-1 for relapse-free survival (RFS) and MFS exploring possible sources of heterogeneity. Nodal status, the most important prognostic factor for breast cancer, introduced heterogeneity in the uPA/PAI-1 survival analyses, reflecting the interaction between nodal status and uPA/PAI-1. The estimates for uPA and PAI-1 were found to be consistent, even when a different transformation of their values was used. The heterogeneity of the separate data sets decreased if the levels of uPA and PAI-1 were ranked, data sets were pooled, and the analyses corrected for the base model that included all traditional prognostic factors, and stratified by data set. We conclude that uPA and PAI-1 are ready to be used in the clinic to help classify breast cancer patients into high and low risk groups.

Breast Neoplasms↗
PubMed2002

Prognostic potential of the telomerase subunit human telomerase reverse transcriptase in tumor tissue and nontumorous mucosa from patients with colorectal carcinoma.

BACKGROUND: The stabilization of telomere lengths by telomerase activation is an important step in carcinogenesis and cell immortalization. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of this enzyme. The objective of this study was to evaluate the use of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for the quantification of hTERT in tumor and nontumorous tissue samples. METHODS: Matched samples of tumor and adjacent nontumorous mucosa samples from 57 patients with completely resected colorectal carcinoma (International Union Against Cancer Stage I-IV) who underwent complete resection (R0) were quantified for hTERT mRNA expression using real-time RT-PCR. The expression levels were correlated with histopathologic findings and with survival. The median follow-up was 76 months. RESULTS: hTERT mRNA was expressed in all tumor samples and in all samples of adjacent mucosa. In 12 patients (21%), there was higher hTERT expression in tumor samples compared with nontumorous samples. Compared with tumor samples, the expression of hTERT in samples of nontumorous mucosa decreased with age (P = 0.06). hTERT mRNA expression in both tumor tissue and adjacent mucosa was correlated significantly with the histologic grade of colorectal carcinoma (P < 0.04 and P < 0.05, respectively). Patients with hTERT expression in tumor tissue in relation to the adjacent mucosa of > 0.57 had a significantly poorer overall survival compared with patients with lower hTERT ratios (P < 0.02). In addition to the established prognostic factor lymphatic vessel invasion, the hTERT ratio proved to be of independent prognostic value (P < 0.05). CONCLUSIONS: The prognostic potential of hTERT in patients with colorectal carcinoma and the correlation of hTERT with tumor grade underlines the role of hTERT as a molecular marker for biologic tumor staging.

Adenocarcinoma↗
PubMed2002

Impact of grade of dysplasia in villous adenomas of Vater's papilla.

Therapeutic strategies for villous adenoma of the papilla of Vater remain controversial. This study evaluates the accuracy of preoperative histopathologic diagnosis and the impact of the grade of dysplasia on recurrence as well as on potential alteration of the surgical approach. A series of 32 patients with an adenoma of Vater's papilla who underwent local resection or pylorus-preserving pancreaticoduodenectomy between January 1990 and August 2000 were reviewed retrospectively. Multiple endoscopic biopsies had been performed preoperatively. The histopathology of the preoperatively obtained biopsy specimens and subsequent surgical specimens were evaluated for grade of dysplasia by two pathologists and correlated with the clinical course after operative treatment. Altogether, 3 of 11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy specimens exhibited invasive carcinoma at the postoperative histologic examination (NS). Recurrence was not observed in the 6 patients from the LG dysplasia adenoma group following local resection and benign postoperative histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12 patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%) from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of the papilla of Vater including HG dysplasia appears to be associated with a high risk of exhibiting invasive carcinoma postoperatively and a high rate of recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be offered to patients with an HG dysplasia adenoma.

Adenoma, Villous↗
PubMed2002

Bone metabolism during the perimenopausal transition: a prospective study.

OBJECTIVE: Changes in biochemical markers of bone formation and resorption were followed over the course of 1 year in premenopausal, perimenopausal and early postmenopausal women. METHODS: Sixty-four subjects were analyzed, grouped according to their menstrual pattern, menopausal complaints and endocrinological parameters to be premenopausal (n=20), perimenopausal (n=24) or early postmenopausal (n=20). The parameters studied at four visits during the 12-month study period were the urinary pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD), and N-terminal telopeptide (NTX) as bone resorption markers, as well as osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) in serum, representing bone formation. The longitudinal changes over time as well as intergroup differences were analyzed using generalized estimating equations (GEE) in connection with Wald statistics. RESULTS: Over the course of 1 year BAP levels decreased in the late premenopausal group (P<0.05). The perimenopausal group exhibited significant changes of PYD, DPD and OC (P<0.01), NTX levels were higher than in premenopause. Postmenopausal subjects had elevated NTX values, while PYD and DPD levels remained close to the perimenopausal range. Only for OC a time effect was seen during postmenopause. CONCLUSIONS: Changes in bone turnover already begin in late premenopause, when decreased bone formation may precede increased bone resorption. The rise of NTX from late premenopause through early postmenopause indicates diagnostic sensitivity of this parameter to changes in bone metabolism induced by estrogen withdrawal. PYD and DPD do not follow this pattern, but change significantly with time during perimenopause to then remain largely unchanged in early postmenopause.

Adult↗
PubMed2002

Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients.

BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. RESULTS: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategies.

Adult↗
PubMed2002

Impaired monocyte IL-12 production before surgery as a predictive factor for the lethal outcome of postoperative sepsis.

OBJECTIVE: To investigate whether monocyte paralysis resistant to interferon-gamma (IFN-gamma) costimulation may exist before surgery and postoperative infection and may correlate with the outcome of postoperative sepsis. SUMMARY BACKGROUND DATA: Several studies have correlated monocyte paralysis during the course of sepsis with lethal outcome. Although the authors' previous work indicated that preoperative defects in monocyte interleukin (IL)-12 production are associated with the development of severe postoperative sepsis, the functional state of monocytes before surgery and infection and its significance for sepsis requires further analysis. METHODS: In a prospective study, monocyte functions of 1,113 consecutive patients were examined before major visceral surgery. Monocytes were isolated from peripheral blood and were stimulated in vitro with IFN-gamma and lipopolysaccharide. The secretion of IL-12 p70, IL-12 p40, IL-10, and tumor necrosis factor was measured. RESULTS: Preoperative monocyte secretion of IL-12 p70 and IL-12 p40 was significantly reduced in patients who developed lethal postoperative sepsis compared with sepsis survivors and patients with uneventful postoperative recovery. Moreover, preoperative monocyte IL-12 production was an independent predictive factor for the lethal outcome of postoperative sepsis by multivariate analysis. Preoperative monocyte IL-10 production was impaired in the sepsis group but did not correlate with death from sepsis. Preoperative monocyte tumor necrosis factor secretion was comparable between patients with uneventful recovery, sepsis survivors, and nonsurvivors. Thus, impaired preoperative monocyte IL-12 secretion in patients developing lethal postoperative sepsis did not result from an overproduction of IL-10 or from a generalized monocyte paralysis. The association between impaired preoperative monocyte IL-12 production and death from sepsis was also not explained by gender differences, underlying malignant disease, tumor type, neoadjuvant therapy, or age. CONCLUSIONS: These results identify a selective preoperative defect in monocyte IL-12 production as a predictive factor for the lethal outcome of postoperative sepsis. These data suggest that a partial preoperative monocyte paralysis severely impairs the host defense against postoperative infection, resulting in an increased risk of lethal sepsis.

Adjuvants, Immunologic↗
PubMed2002

Differential regulation of systemic IL-18 and IL-12 release during postoperative sepsis: high serum IL-18 as an early predictive indicator of lethal outcome.

Systemic levels of the key immune regulatory cytokines IL-12 and IL-18 were measured over time in 66 patients with postoperative sepsis (38 survivors and 28 nonsurvivors). Sepsis mortality was not significantly associated with any of the clinical parameters examined, including age, gender, underlying disease, and surgical procedure. Analysis of cytokine levels showed that during the entire observation period, IL-12 was significantly reduced in sepsis patients compared with control surgical patients without sepsis. IL-12 serum levels did not significantly differ between sepsis survivors and nonsurvivors. In contrast to IL-12, IL-18 serum levels were significantly higher in both surviving and nonsurviving sepsis patients than in controls. Importantly, we also observed that IL-18 levels were significantly increased in patients with lethal sepsis compared with sepsis survivors at all time points studied, including day 1 after sepsis diagnosis. IL-18 levels were significantly increased during the course of lethal sepsis, but remained at a comparable level in sepsis survivors. Logistic regression analysis of IL-18 values measured on days 1 or 2 of sepsis revealed that high serum IL-18 represents an early predictive factor for the lethal outcome of postoperative sepsis. Consistent with previous work in mouse models, our results suggest that IL-12 may contribute to protective immune reactions against a septic challenge, whereas IL-18 may preferentially promote organ injury and lethal shock.

Aged↗
PubMed2002

Atrial mechanical performance after internal and external cardioversion of atrial fibrillation: an echocardiographic study.

OBJECTIVES: To compare the time course of resumption of mechanical performance of the left and right atrium after the novel method of internal low-energy cardioversion (CV) and conventional external CV of atrial fibrillation (AF). BACKGROUND: Right atrial performance has been shown to normalize before the left atrium after external CV. However, no data on atrial function after internal CV are available. PATIENTS AND INTERVENTIONS: Sixty-three patients with chronic AF were randomized to participate in either external or internal CV. MEASUREMENTS: Echocardiographic examinations were carried out before as well as immediately after CV (day 0), and at days 1, 7, and 28 thereafter for the determination of cardiac dimensions, volumes, and transvalvular flow patterns. RESULTS: After randomized internal CV or external CV, stable sinus rhythm was restored in 59 patients. Irrespective of the mode of CV, the right atrium resumed its mechanical function immediately after CV, whereas the left atrium was stunned beyond day 7. The mode of CV, internal or external, had no influence on the recovery of atrial mechanical function. CONCLUSIONS: The right atrium resumes its normal function immediately after internal as well as external CV, whereas left atrium function is delayed. In contrast to the assumption that low-energy internal CV would impact less on atrial mechanical recovery, the type of method of CV used has no effect on such recovery.

Aged↗
PubMedDate not supplied

Changes in the circulating plasma levels of VEGF and VEGF-D after adjuvant chemotherapy in patients with breast cancer and 1 to 3 positive lymph nodes.

BACKGROUND: The goal of the present study was to investigate the changes in concentration of the important lymph-angiogenesis factors vascular endothelium-derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy. MATERIALS AND METHODS: The blood plasma of a total of 142 patients with breast carcinoma and with 1 to 3 affected lymph nodes was investigated, using the quantitative sandwich enzyme immunoassay technique, prior to and following chemotherapy, within the framework of a randomized phase III study: the patients received either conventional or dose-intensified chemotherapy. RESULTS: In general, there was a significant reduction in VEGF levels after chemotherapy only in patients with large tumors (T3) (p = 0.043). There was also an almost significant reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p = 0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a positive hormone receptor status (p = 0.04) or in patients with a low expression of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on VEGF-D was determined only in patients who had a baseline level that was above the normal (conventionel treatment p = 0.005; dose-intensified treatment p = 0.004). CONCLUSION: Both VEGF and VEGF-D levels changed after chemotherapy, depending on the patient and tumor characteristics. With respect to changes in the plasma levels of VEGF and VEGF-D, there were no significant differences between dose-intensified and conventional chemotherapy.

Adult↗