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Biomedical subjects

A de Boer

Publications and source records attributed to A de Boer.

At least 73 records · Page 4Linked to original sources
PubMed1997

Dispensing epilepsy medication: a method of determining the frequency of symptomatic individuals with seizures.

We estimated the prevalence and incidence of epilepsy in The Netherlands using drug-dispensing information from the PHARMO database, containing medication histories of nearly 300,000 individuals. An algorithm based on antiepileptic drug prescription records was used to identify patients with epilepsy requiring medication for seizure control. The algorithm was validated by comparing positive algorithm identifications to medical diagnoses from general practitioners and hospital records. In 1990-1991, the algorithm revealed 1158 patients with "certain" epilepsy, and 451 patients with "probable" epilepsy. Epilepsy was present in 93% of patients on polytherapy, and 58% on monotherapy. Clonazepam monotherapy was non-specific for epilepsy. The use of carbamazepine monotherapy for epilepsy was age-dependent. After correcting the algorithm for these drugs, and standardizing to the Dutch population, the point prevalence of epilepsy was 4.8/1000 (95% CI: 4.5-5.0). The incidence rate was 0.72/1000 person-years (95% CI: 0.65-0.79). Using drug-dispensing data for epilepsy medication, it is possible to make valid estimations of the number of epilepsy patients requiring drug therapy.

Adolescent↗
PubMed1997

Cardio-pulmonary-bypass time has important independent influence on mortality and morbidity.

OBJECTIVE: To determine the influence of cardio-pulmonary-bypass-time on hospital mortality and ICU-morbidity in isolated CABG surgery. METHODS: Between 1985 and 1994 perioperative data of 8578 consecutive CABG operations were prospectively collected. Seven variables: gender, redo vs. primary operation, elective vs. urgent surgery, age in 4 categories, use of IMA, number of distal anastomoses (> 4 vs. < = 4), and cardio-pulmonary-bypass-time in four categories were entered in multivariate logistic regression analysis and odds ratios for respective cardio-pulmonary-bypass-time-categories with regard to mortality, length-of-stay in the ICU and 8 ICU-complications were calculated. Bypass-time up to 90 min was the reference category, the other categories were from 1.5 to 2.5 h, 2.5 to 3.5 h, and longer than 3.5 h. RESULTS: 8337 operations had complete data. Mortality and ICU-morbidity were low. The odds ratios for mortality were 2.3 (P = 0.0094), 7.4 (P < 0.0001) and 20.7 (P < 0.0001) for ascending bypass-time-categories. The odds ratios for prolonged ICU-stay were 1.8 (P = 0.0002), 3.3 (P < 0.0001) and 7.9 (P < 0.0001) for ascending bypass-time-categories. For postoperative complications the same pattern was found: consequently higher odds ratios for longer bypass-time-categories. CONCLUSION: The highly significant correlation between cardio-pulmonary-bypass-time-category and the occurrence of undesirable postoperative events is demonstrated by the consequent rise in odds ratios. This independent influence of cardio-pulmonary-bypass-time on outcome reflects both problems encountered during revascularisation and time-related influence of cardio-pulmonary-bypass on the human body. When a predictive model was created, CPBT proved to be a good predictor of undesirable postoperative events.

Adult↗
PubMed1997

Sex differences in the pharmacological treatment of hypertension: a review of population-based studies.

OBJECTIVE: To summarize all available literature on sex differences in the pharmacological treatment of hypertension with respect to the percentage of hypertensive patients treated pharmacologically and the selection of antihypertensive drugs. The influences of the calendar period, age, definition of hypertension, prevalence of hypertension and country on these sex differences were examined. DATA IDENTIFICATION: A secondary analysis of data from 46 population-based studies in 22 countries on the prevalence of pharmacologically treated hypertension was conducted to estimate sex ratios for the prevalence of drug treatment for hypertension. RESULT: Overall, women with hypertension were 1.33-fold [95% confidence interval (CI) 1.32-1.34] more likely to be treated pharmacologically for hypertension than were hypertensive men. With increasing age, the female: male ratio for pharmacological treatment of hypertension decreased from 2.26 (95% CI 1.56-3.27) at ages 20-29 years to 1.22 (95% CI 1.11-1.34) at ages 60-69 years. In all countries more women than men were treated for hypertension, with the biggest difference observed in the USSR (1983-1986), where about twice as many women as men were treated for hypertension. Women more frequently used diuretics, whereas men more often used beta-blockers, angiotensin converting enzyme inhibitors and calcium antagonists. CONCLUSIONS: Hypertensive women are more often treated for hypertension than hypertensive men and their pattern of use of antihypertensive drugs differs from that of men. Further research is required in order to explain sex differences in the treatment of hypertension with respect to the prevalence of pharmacological treatment of hypertension and choice of antihypertensive drugs, and to investigate the consequences of this difference for long-term outcomes.

Adult↗
PubMed1997

Ultraviolet exposure and the development of banal and atypical naevi--a cross-sectional study on Curaçao and in The Netherlands.

The atypical naevus is both a risk factor for and a precursor lesion of melanoma. Sunlight is known to be an important aetiological factor for melanoma. Whether solar exposure is also involved in the initiation of (atypical) naevi is an issue of current interest. We performed a cross-sectional study among 270 inhabitants in the cloudy Netherlands and 282 white Dutch immigrants of the tropical island Curaçao to investigate whether solar exposure plays a role in the development of atypical naevi. All participants were interviewed and underwent total skin examination; banal melanocytic naevi and atypical naevi were counted. There was no significant difference in the mean number of melanocytic naevi > or = 2 mm or > or = 5 mm between Curaçao and the Netherlands. Furthermore, there was no significant difference in the mean crude and age standardized prevalence of atypical naevi between the Netherlands and Curaçao. In both groups individuals with atypical naevi had significantly more total naevi. Concerning the role of sun exposure in the development of naevi in the Netherlands, we found that the total naevus count had a significant association with cumulative sun exposure before the age of 12 as well as with two or more painful sunburns before the age of 12. In Curaçao these relationships were not observed. In contrast, however, on Curaçao the presence of atypical naevi showed an association (odds ratio = 2.6, 95% confidence interval 1.1-6.0) with the highest level of cumulative sun exposure and with painful sunburns before the age of 12 (odds ratio = 2.6, 95% confidence interval 1.2-5.5). In the Dutch group these associations were not significant. We hypothesize that in the development of banal naevi there is an association between the total number of naevi and sun exposure only at low exposure levels; however, after overstepping a critical threshold a further association between melanocytic naevi and sun exposure is lacking. Sunlight exposure before the age of 12 plays a complex role: only very high exposure levels seem to contribute to the development of atypical naevi.

Adolescent↗
PubMed1997

Postpneumonectomy pulmonary edema. A retrospective analysis of incidence and possible risk factors.

OBJECTIVE: To analyze the incidence of postpneumonectomy pulmonary edema (PPE) and to determine potential risk factors for PPE. MATERIAL AND METHODS: A group of 197 patients was studied retrospectively, and the incidence of PPE was recorded over a 5-year period. Preoperative, perioperative, and postoperative clinical data were collected, and preoperative and postoperative chest radiographs were reviewed. A scoring system was used to distinguish between premanifest and manifest PPE. Postpneumonectomy patients with pulmonary edema, with no clinically evident cause, were considered to have PPE. RESULTS: The incidence of premanifest PPE was 12.2% (n = 24), and that of manifest PPE was 2.5% (n = 5). Mortality in the group of patients who developed manifest PPE was 100%. Two significant perioperative associations were found in the PPE group. One was the administration of fresh frozen plasma (FFP) transfusions (relative risk, 4.3; 95% confidence interval, 1.3 to 14.4 corrected for age and sex), while the other was higher mechanical ventilation pressures during surgery (relative risk, 3.0; 95% confidence interval, 1.2 to 7.3). CONCLUSION: Our data suggest that FFP transfusions form an important risk factor for PPE. The mechanism may be an increased permeability of the pulmonary vessels due to an immunologic reaction after multiple FFP transfusions. The significantly higher mechanical ventilation pressures we found in the PPE group may be explained as an early sign of the development of PPE.

Adult↗
PubMed1996

[The first case of Crigler-Najjar syndrome in the Czech Republic].

BACKGROUND: Crigler-Najjar syndrome is a rare disease due to a congenital deficiency of bilirubin UDP glucuronosyl transferase in the liver tissue. It is characterised by high levels of unconjugated bilirubin in plasma through the whole life. The aim of the study was to confirm the clinical diagnosis of the first Crigler-Najjar syndrome case in our country. METHODS AND RESULTS: 34 years old Gypsy women was admitted to our GI clinic for clinical examination before scheduled cholecystectomy. The high plasmatic level of unconjugated bilirubin was found and therefore the diagnosis of Crigler-Najjar syndrome was anticipated. The diagnosis was based on the chromatographic analysis of biliary bile pigments. The amount of diconjugates was considerable decreased. In addition, the molecular analysis of DNA isolated from peripheral blood leukocyte was performed to confirm our conclusions. Our patients was found to be homozygous for a nucleotide shift in the unique exon of bilirubin UDP glucuronosyl transferase 1, substituting guanine into an adenine at position 211.

Adult↗
PubMed1996

Non-compliance in elderly people: evaluation of risk factors by longitudinal data analysis.

Studies on risk factors for drug non-compliance have not taken into account the possibility of correlated outcomes. We therefore conducted a study into risk factors for non-compliance by using analysis techniques that adjust for these correlations (longitudinal data analysis). Data were obtained from interviews and pharmacy records in a cross-sectional survey in Amsterdam. The subjects were 157 elderly people aged 70 years or older. Of these subjects, 37 were residents of a home for the elderly, 40 were community-dwelling elderly who needed to be visited regularly by a district nurse, and 80 were community-dwelling elderly who did not need to be visited by a district nurse. Most drugs (78%) were used according to the directions; the remainder (22%) were not used as intended. Odds ratios (95% confidence intervals) for non-compliance for moderate and poor/wrong knowledge of the purpose of a drug as compared with good/correct knowledge were 2.8 (1.2-6.7) and 4.2 (1.5-12), respectively. Drug regimens of two times daily and more than two times daily were associated with odds ratios for non-compliance of 4.5 (1.6-12) and 4.2 (1.7-11), respectively, compared to a regimen of once daily. Compliance increased if a drug was prescribed by a specialist instead of a general practitioner odds ratio 0.1 (0.04-0.4)]. There was no significant relation between compliance and the number of drugs prescribed to a patient, sex, age, living situation, patient group, or perceived effect. This study, which was based on longitudinal data analysis, demonstrates that in elderly people non-compliance with drug therapy is related to the knowledge of purpose of a drug, the complexity of a drug regimen, and the type of prescriber. The positive association between compliance and the number of drugs prescribed found in former studies was not confirmed.

Aged↗
PubMed1996

Selective decontamination of the digestive tract: effect of cessation of routine application at an ICU.

BACKGROUND: Selective decontamination of the digestive tract (SDD) with non-absorbable antibiotics was extensively used at intensive care units (ICU) in Europe to prevent nosocomial infections in critically ill patients. After three recent meta-analyses in which it was demonstrated that SDD did not influence hospital stay and mortality in these patients several ICU's decided to stop the routine use of SDD. OBJECTIVE: To examine the effects of the cessation of SDD on nosocomial infections, mortality and hospital stay at an ICU in post-operative patients. DESIGN: Retro- and prospective follow-up. PATIENTS: Post-operative patients with mechanical ventilation (MV) for > or = 5 days at an ICU were included. The retrospective group (SDD group) comprised of 138 patients (mean age 66, range 10-91; 78% male) and the prospective group (non-SDD group) of 142 patients (mean age 67 range 18-85; 65% male). The SDD regime consisted of colistin, tobramycin and amphotericin B. Cessation of the SDD was accompanied by a shortening of the routine intravenous cefuroxime prophylaxis. RESULTS: There was a nonsignificant increase from an average 21 to 23 days ICU stay in the non-SDD group when compared with the SDD group (p > 0.05). Of the 280 patients 97 (35%) died on the ICU. The risk of death was lower in the non-SDD group (adjusted hazard ratio 0.7 with 95% Cl 0.5-1.1). There was a trend towards an increase in infections as a cause of death in the non-SDD group (38% of the ceased patients versus 20% in the SDD group) (p > 0.05). The incidence of respiratory tract infection (per 1000 person days) was 80 (95% Cl 48-113) in the non-SDD group versus 19 (95% Cl 8-22) in the SDD group (adjusted hazard ratio 4.5 (95% Cl 2.9-7.1)). CONCLUSION: The cessation of the routine application of SDD in post-operative patients mechanically ventilated for 5 days or more did nod adversely affect survival nor increased length of stay at the ICU. There may have been a shift to infections as a cause of death after cessation of SDD.

Adolescent↗
PubMed1996

Current use of thiazide diuretics and prevention of femur fractures.

A case control study of a defined population from The Netherlands was performed to evaluate the risk of femur fractures associated with the use of thiazide diuretics. Included were 386 patients hospitalized for femur fractures between 1986 and 1990 who were residents and 45 years of age and older. Per case, one age-, sex-, pharmacy-, and general practitioner-matched control was chosen from the general population. Drug use was ascertained from computerized pharmacy records. The adjusted odds ratio of current use of thiazide diuretics was 0.5 (95% confidence interval, 0.3-0.9). The protective effect of thiazide diuretics was greatest for use of 1 year or longer at relatively high doses of thiazides (odds ratio, 0.3; 95% confidence interval, 0.1-0.9). We also found that patients who discontinued thiazide use longer than 2 months were not protected against femur fractures. These results support the hypothesis that use of thiazide diuretics protects against femur fractures.

Aged↗
PubMed1995

The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome.

BACKGROUND: People with Gilbert's syndrome have mild, chronic unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis. Hepatic glucuronidating activity, essential for efficient biliary excretion of bilirubin, is reduced to about 30 percent of normal. METHODS: We sequenced the coding and promoter regions of the gene for bilirubin UDP-glucuronosyltransferase 1 (bilirubin/uridine diphosphoglucuronate-glucuronosyltransferase 1)--the only enzyme that contributes substantially to bilirubin glucuronidation--in 10 unrelated patients with Gilbert's syndrome, 16 members of a kindred with a history of Crigler-Najjar syndrome type II, and 55 normal subjects. RESULTS: The coding region of the gene for the enzyme was normal in the 10 patients with Gilbert's syndrome. These patients were homozygous for two extra bases (TA) in the TATAA element of the 5' promoter region of the gene (A(TA)7TAA rather than the normal A(TA)6TAA). The presence of the longer TATAA element resulted in the reduced expression of a reporter gene, encoding firefly luciferase, in a human hepatoma cell line. The frequency of the abnormal allele was 40 percent among the normal subjects. The 3 men in the control group who were homozygous for the longer TATAA element had significantly higher serum bilirubin levels than the other 52 normal subjects (P = 0.009). Among the kindred with a history of Crigler-Najjar syndrome type II, only the six heterozygous carriers who had a longer TATAA element on the structurally normal allele had mild hyperbilirubinemia, characteristic of Gilbert's syndrome. CONCLUSIONS: Reduced expression of bilirubin UDP-glucuronosyltransferase 1 due to an abnormality in the promoter region of the gene for this enzyme appears to be necessary for Gilbert's syndrome but not sufficient for the complete manifestation of the syndrome.

Adolescent↗
PubMed1995

Benzodiazepines and the risk of falling leading to femur fractures. Dosage more important than elimination half-life.

BACKGROUND: In the past decade, the use of benzodiazepines has been identified as a major independent risk factor for accidental falls. OBJECTIVE: To study the role of dosing, timing, elimination half-life, and type of benzodiazepine in relation to the occurrence of accidental falls leading to hospitalization for femur fractures. METHODS: A 1:3 age-, sex-, and pharmacy-matched case-control study was performed using data from a Dutch record linkage system (PHARMO) (N = 300,000). Cases included 493 patients (55 years and older), newly admitted to the hospital for a femur fracture resulting from an accidental fall (between 1986 and 1992). Relative risk estimates were calculated using conditional logistic regression analyses to control for the potential confounding effects of concomitant drug use and presence of a wide range of underlying diseases. RESULTS: Falls were significantly associated with current use of benzodiazepines (odds ratio, 1.6; 95% confidence interval, 1.2 to 2.1) and in particular with short half-life benzodiazepines (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0), sudden dose increases (odds ratio, 3.4; 95% confidence interval, 1.0 to 11.5), and concomitant use of several benzodiazepines (odds ratio, 2.5; 95% confidence interval, 1.3 to 4.9). A strong dose-response relationship (P < .0001) and dose-response relations among users of either short or long half-life benzodiazepines suggests that these increased risks are explained primarily by dose. CONCLUSIONS: Benzodiazepines are a major, independent risk factor for falls leading to femur fractures, and the increased risk is probably explained by prescribing too-high doses to the elderly.

Accidental Falls↗
PubMed1995

Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme.

The use of angiotensin-converting-enzyme (ACE) inhibitors has been associated with increased insulin sensitivity in diabetic patients. Although such an effect could be beneficial in the treatment of hypertension or congestive heart failure in diabetic patients, it might also precipitate severe hypoglycaemia. To test this hypothesis we carried out a nested case-control study, using data in the Dutch PHARMO system (1986-92), among diabetic patients treated with insulin or with oral antidiabetic drugs, who were admitted to hospital with hypoglycaemia. We identified 94 patients who had been admitted with hypoglycaemia and selected 654 controls from the same cohort. With adjustment for a wide range of potential confounding factors, hypoglycaemia was significantly associated with current use of ACE inhibitors (odds ratio 2.8 [95% CI 1.4-5.7]). Both among users of insulin and among users of oral antidiabetic drugs, use of ACE inhibitors was significantly associated with an increased risk of hospital admission for hypoglycaemia (2.8 [1.2-6.4] and 4.1 [1.4-12.2], respectively). Although ACE inhibitors have several advantages over other antihypertensive drugs in diabetes, the risk of hypoglycaemia should be taken into account. Further investigation of the mechanism is needed since as many as 13.8% of all hospital admissions for hypoglycaemia might be attributable to use of ACE inhibitors.

Adult↗
PubMed1995

A rapid method to estimate the incidence rate and prevalence of insulin-dependent diabetes mellitus in children 0-19 years of age.

OBJECTIVE: To trace new cases of insulin-dependent diabetes mellitus (IDDM) on an ongoing basis and to estimate the incidence rate and prevalence of IDDM in children 0-19 years of age. RESEARCH DESIGN AND METHODS: The estimation of the prevalence and incidence rate of IDDM was based on, respectively, the prevalence and the rate of new users of insulin. The data were obtained from pharmacy, patient-based, drug dispensing histories in a well-defined population encompassing 257,113 individuals in the Netherlands. RESULTS: The IDDM incidence rate was estimated at 11.5 (CI95 6.6-17.8) per 100,000 person years in 1989-1990 in children 0-19 years of age. The prevalence was estimated at 11.0 (CI95 8.6-13.4) per 10,000 children 0-19 years of age. DISCUSSION: The incidence rate is comparable to that found in a large, national survey among all paediatricians and internists in the Netherlands. The method offers ongoing monitoring of the incidence and prevalence of IDDM in children, 0-19 years of age, against low costs. The method is suitable for rapid and cost-efficient recruitment of cohorts of incident IDDM patients, which fosters research to identify and quantify the attribution of different types of aetiologic and prognostic factors of IDDM.

Adolescent↗
PubMed1995

Determination of a maximum number of artificial inseminations by donor children per sperm donor.

OBJECTIVE: To determine a safe maximum number of artificial insemination (donor insemination [DI]) children per anonymous sperm donor. DESIGN: Multiparameter calculation model of contribution of DI to inbreeding. SETTING: Data of the collaborative DI centers and demographic population data of The Netherlands. INTERVENTIONS: Calculations of the contribution of DI to inbreeding were made, taking into account all possible unintentional consanguineous matings and consanguineous inseminations with a coefficient of inbreeding (F) of > or = 1/16 for the offspring. MAIN OUTCOME MEASURE: Coefficient of inbreeding (F). RESULTS: The contribution of DI to inbreeding was estimated to be 46.6 x 10(-6) + k (1.66 x 10(-6)) (k = number of DI children per donor). When only half-sibling matings were considered, the kmax was 32. When all possible consanguineous matings and inseminations were taken into account, kmax decreased with 28% to 25 children. CONCLUSION: Calculations of a maximum number of DI children per sperm donor, based on possible enhancement of inbreeding and given the Dutch population and DI setting, show that 25 children per DI donor is a safe threshold for clinical practice.

Consanguinity↗
PubMed1995

A comparative study of atypical and melanocytic naevi on the tropical island Curaçao and in The Netherlands.

A cross-sectional study was undertaken in 270 inhabitants of The Netherlands (moderate maritime climate, latitude 51 degrees 5' N-53 degrees 3' N) with skin types I-III and 757 inhabitants of the tropical island Curaçao (latitude 12 degrees 2' N-12 degrees 23' N). The latter group consisted of 282 White individuals (mostly Dutch immigrants) and 475 people with non-White skin types IV, V and VI. All participants underwent total skin examination and melanocytic naevi (MN) and clinically atypical naevi (AN) were noted. There was no statistical difference in the mean number of naevi > or = 2 mm or > or = 5 mm between the Curaçao and The Netherlands White groups, but the mean number of naevi > or = 2 mm and > or = 5 mm was significantly lower in the Curaçao non-White group. We found no obvious differences in mean naevus counts between genders and the various comparable age groups. Furthermore, we found no significant difference in mean crude and mean age-standardized prevalence of (one or more) AN between Whites in The Netherlands and on Curaçao. The Mantel-Haenszel prevalence ratio weighted for age and gender differences of Curaçao Whites vs non-Whites was 5.93 (95% confidence interval 3.9-12.0), demonstrating that AN are significantly less prevalent in darker skin types. In all groups, people with AN had significantly more MN than people without AN. We found a generation-dependent difference in the expression of AN among White inhabitants of The Netherlands and on Curaçao, with a higher prevalence of AN in the younger generation.

Adolescent↗
PubMed1995

Drug interactions with thrombolytic agents. Current perspectives.

Thrombolytic agents are widely used for the treatment of acute thromboembolic diseases, especially acute myocardial infarction (AMI). These compounds include streptokinase, anistreplase, alteplase, urokinase and, although not commercially available yet, saruplase (prourokinase). The therapeutic window of these compounds is relatively small and subtherapeutic or toxic plasma concentrations may have serious clinical implications (insufficient thrombolysis, reocclusion and bleeding). Among the factors that affect the pharmacokinetics and pharmacodynamics of thrombolytic agents, comedication is especially relevant since these drug interactions are partly predictable and sometimes preventable. Based on knowledge of the pharmacology of thrombolytic agents and general mechanisms by which pharmacokinetic drug interactions occur, interactions with alteplase and saruplase are expected. The clearance of alteplase is dependent on hepatic blood flow (HBF), and scientific evidence is emerging that saruplase is also a high-clearance compound. Each pharmacological agent that alters HBF and is given concurrently with one of these agents can change the plasma concentrations of those thrombolytics. Although there are no published data confirming drug-induced changes in the metabolism of alteplase or saruplase by this mechanism in humans, indirect supportive evidence (clinical observations and animal experiments) is available. An overview is presented of the anticipated effects of compounds that are frequently coadministered with thrombolytic agents on the pharmacokinetics of the thrombolytics with high-clearance properties. Since the clearance of these thrombolytics may be strongly affected by hypoperfusion of the liver as a result of cardiogenic haemodynamic failure, the role of circulatory changes in potential drug-drug interactions is also discussed. Pharmacodynamic drug interactions are highly relevant in the treatment of acute thrombotic lesions and are still being evaluated to further optimise treatment strategies. As most of these treatments exist as combinations of thrombolytic, antithrombin and antiplatelet compounds, beneficial effects are partly offset by bleeding complications. Changes in the pharmacokinetics and/or pharmacodynamics of thrombolytic agents may have serious consequences. It becomes imperative for the practising physician to be aware of benefits and risks of interactions with thrombolytic agents and especially of the fact that the principal way by which the pharmacokinetics of alteplase and, presumably, saruplase can be affected is by drug- and/or haemodynamic failure-induced changes of HBF.

Drug Interactions↗
PubMed1994

Prognostic relevance of plasminogen activators and their inhibitors in colorectal cancer.

Human colorectal carcinogenesis has been shown previously to be associated with impressive changes in the tissue levels of plasminogen activators and their inhibitors, exemplified by an increase in the urokinase-type plasminogen activator (u-PA) and the inhibitors PAI-1 and PAI-2, and a decrease in tissue-type plasminogen activator (t-PA). In the present study we evaluated the prognostic significance of these parameters to the overall survival of patients with colorectal cancer, in conjunction with several major clinicopathological parameters like age, gender, differentiation grade, and Dukes' stage. Univariate analyses revealed that a low t-PA antigen level, low t-PA activity, and high u-PA/t-PA antigen ratio in normal mucosa and a high u-PA and PAI-2 antigen level in carcinomas are prognostic for a poor overall survival of patients with colorectal cancer. The prognostic value of t-PA antigen and activity in normal mucosa, the antigen ratio of u-PA in carcinoma (C) and t-PA in corresponding normal (N) mucosa [u-PA(C)/t-PA(N) antigen ratio], and PAI-2 antigen in carcinomas was found to be independent from clinicopathological parameters by multivariate analyses. These observations illustrate the clinical importance of the plasminogen activation cascade at the tissue level in colorectal cancer invasion, metastasis, and survival.

Aged↗