Contribution of plasminogen activators and their inhibitors to the survival prognosis of patients with Dukes' stage B and C colorectal cancer

Despite the advances in pre-, peri- and post-operative medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In previous studies we found that colorectal carcinomas have a marked increase of the urokinase-type of plasminogen activator (u-PA), and the inhibitors PAI-1 and PAI-2, whereas the tissue-type plasminogen activator (t-PA) is found to be decreased in comparison with adjacent normal mucosa. In the present study we evaluated the prognostic value of several plasminogen activation parameters, determined in both normal and carcinomatous tissue from colorectal resection specimens, for overall survival of 136 Dukes' stage B and C colorectal cancer patients, in relation to major clinicopathological parameters. Uni- and multivariate analyses indicated that a high PAI-2 antigen level in carcinoma, a low t-PA activity and antigen level and a high u-PA/t-PA antigen ratio in adjacent normal mucosa are significantly associated with a poor overall survival. A high ratio of u-PA antigen in the carcinomas and t-PA antigen in normal mucosa, i.e. u-PA(C)/t-PA(N), was found to be predictive of a poor overall survival as well. All these parameters were found to be prognostically independent of the clinicopathological parameters. Multivariate analysis of combinations of these prognostically significant plasminogen activation parameters revealed that they are important independent prognostic indicators and have in fact a better prognostic value than their separate components. Based on these combined parameters, subgroups of patients with Dukes' stage B and C colorectal cancer could be identified as having either a high or a low risk regarding overall survival. In conclusion, these findings emphasize the relevance of the intestinal plasminogen activation system for survival prognosis of patients with colorectal cancer and, in the future, might constitute a patient selection criterion for adjuvant therapy.     

Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography

An isocratic high-performance liquid chromatographic method with ultraviolet detection was utilized for the investigation of the pharmacokinetics of naringenin and its glucuronide conjugate in rat plasma and brain tissue. Plasma and brain tissue were deproteinized by acetonitrile, then centrifuged for sample clean-up. The drugs were separated by a reversed-phase C18 column with a mobile phase consisting of acetonitrile-orthophosphoric acid solution (pH 2.5-2.8) (36:64, v/v). The detection limits of naringenin in rat plasma and brain tissue were 50 ng/ml and 0.4 microg/g, respectively. The glucuronide conjugate of naringenin was evaluated by the deconjugated enzyme beta-glucuronidase. The naringenin conjugation ratios in rat plasma and brain tissue were 0.86 and 0.22, respectively, 10 min after naringenin (20 mg/kg, i.v.) administration. The mean naringenin conjugation ratio in plasma was approximately four fold that in brain tissue.     

Range of motion and complications after postburn heterotopic bone excision about the elbow

OBJECTIVE: To review the results of surgical management of heterotopic ossification about the elbow in burned patients. DESIGN: Retrospective analysis with long-term patient follow-up. MATERIALS AND METHODS: Eleven patients with 16 elbows requiring surgery were admitted between January 1, 1982 and December 31, 1993. A posterior approach to the elbow with release of the encased ulnar nerve +/- anterior transposition and transolecranon osteotomy to access extensive bone formation in the olecranon fossa was employed. Eight patients (11 elbows) were available for long-term follow-up conducted at mean 50 +/- 13 months after surgery. Long-term follow-up consisted of measurement of range of elbow motion, as well as clinical assessment of ulnar nerve function. MAIN RESULTS: For the 11 elbows examined postoperatively, the mean range of motion preoperatively in flexion-extension was 11 degrees +/- 5 degrees compared to 89 degrees +/- 12 degrees postoperatively (p < 0.001). Three patients with poor long-term results had ankylosis of the joint preoperatively. Of four patients with ulnar nerve paresis preoperatively, none had ulnar nerve dysfunction at follow-up. Of 16 elbows operated on, four (25%) had postoperative complications. Two suffered soft-tissue breakdown with hardware exposure requiring abdominal flap closure, one early failure of olecranon fixation, and one late infected hardware. CONCLUSIONS: Surgery for both limited range of motion as well as ulnar nerve compression is effective in cases of heterotopic ossification about the elbows of burned patients. Early operative intervention is indicated in progressive disease, particularly ulnar nerve palsy, if soft-tissue quality is adequate. Complications with 25% of elbows suggest that use of olecranon osteotomy for joint access may warrant review.     

Stability of linear discrete switched systems with delays based on average dwell time method

This paper deals with the problem of exponential stability for a class of linear discrete switched systems with constant delays.The switched systems consist of stable and unstable subsystems.Based on the average dwell time method, some switching signals will be found to guarantee exponential stability of these systems.The explicit state decay estimation is also given in the form of the solutions of linear matrix inequalities(LMIs).An example relating to networked control systems(NCSs) illustrates the effect...