Fibrinogen levels in hypercholesterolemic smokers and non-smokers in relation to age and gender.

Elevated total cholesterol and plasma fibrinogen levels and smoking are risk factors for cardiovascular disease, whose inter-relationships are influenced by both gender and age. The aim of this study was to investigate the effect of smoking on fibrinogen levels in a hypercholesterolemic population subdivided on the basis of gender and age. The study included 492 hypercholesterolemic subjects, divided into four subpopulations: men and women, aged 26-49 and 50-66 years. Mean fibrinogen levels among smokers and non-smokers in the four subpopulations of this hypercholesterolemic cohort followed mean total cholesterol levels. Three subpopulations (men <50 years, men >/=50 years and women >/=50 years) showed differences in mean total cholesterol and fibrinogen values between smokers and non-smokers (total cholesterol 7.23+/-0.54 vs. 7.40+/-0.93 mmol/l and fibrinogen 2.79+/-0.48 vs. 3.23+/-0.72 g/l in men <50 years; total cholesterol 7.17+/-0.43 vs. 7.50+/-0.60 mmol/l and fibrinogen 3.11+/-0.44 vs. 3.68+/-0.66 g/l in men >/=50 years and 7.41+/-0.59 vs. 7.65+/-0.73 mmol/l and fibrinogen 3.29+/-0.61 vs. 3.58+/-0.71 g/l in women >/=50 years). These values correspond to a percentage difference between smokers and nonsmokers in total cholesterol and fibrinogen of 2.4% and 15.8% in men <50 years, 4.6% and 18.3% in men >/=50 years and 3.2% and 8.8% in women >/=50 years. All differences were significant ( P<0.05), except for total cholesterol in the younger men (<50 years). No differences between smokers and non-smokers were observed in the younger female group (<50 years). Except in the younger female group (<50 years), significant differences between smokers and non-smokers were also observed in the number of subjects exceeding the upper reference value of fibrinogen (>4.0 g/l), the highest percentage being found for the older women smokers (>/=50 years) (29%). In Conclusion, smoking elevates fibrinogen levels in hypercholesterolemic men (<50 years; >/=50 years) and older women (>/=50 years), but not in younger women (<50 years).

Relationship between smoking habits and low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides in a hypercholesterolemic adult cohort, in relation to gender and age.

Elevated total cholesterol, the related low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and smoking habits are risk factors for cardiovascular disease. The objective of this study was to investigate the influence of habitual smoking on these parameters in 492 hypercholesterolemic men and women, aged between 26 and 66 years. Relative differences between smokers and non-smokers in the mean values of total cholesterol, low-density and hig-density lipoprotein-cholesterol, and triglycerides were 2.2%, 5.5%, -8.1%, and 13.7%, respectively. These differences were statistically significant (P<0.04). Over the entire cohort, including men and women, age did not affect the mean values significantly, except for total cholesterol and triglyceride values in smoking women, which were significantly higher in women over 50 years than in the younger women (P=0.011 and P=0.004). In both men and women, regardless of smoking habits, 43%-59% of subjects exceeded the upper reference range value for low-density lipoprotein-cholesterol (4.9 mmol/l), while 38%-59% exceeded the upper reference range value for triglycerides (2.0 mmol/l) and 82%-91% had values below the lower reference range value for high-density lipoprotein-cholesterol (0.9 mmol/l for men, 1.2 mmol/l for women). Smoking habits hardly influenced the extent to which reference values were exceeded, except for low-density lipoprotein-cholesterol in all subjects (higher percentage for smokers, P=0.041). Similar results were obtained for age, except for triglycerides in smoking women, wich showed high values in 26% of women <50 years versus 50% of women > or = 50 years (P=0.026). In conclusion, smoking has an adverse effect on low-density and high-density lipoprotein-cholesterol, and triglycerides in a hypercholesterolemic population of men and women, regardless of age.

Folic acid, Vitamin B(12), and homocysteine in smoking and non-smoking pregnant women.

INTRODUCTION: Lower plasma levels of vitamins may result in hyperhomocysteinemia, a known risk factor in pregnancy. As smoking may alter nutrition, we were interested in its effect on folate and Vitamin B(12) in pregnancy. MATERIALS AND METHODS: A cross-sectional study of 62 smoking and 76 non-smoking healthy pregnant women. Serum folic acid, Vitamin B(12) and homocysteine were measured at four points in pregnancy: 0-10, 11-20, 21-30 and 31-40 weeks. RESULTS: Folate concentrations of the smoking women decreased continuously during pregnancy, and were significantly lower than those of non-smoking women during the last 30 weeks. Vitamin B(12) levels decreased significantly in both groups. The homocysteine levels were higher in the smoking group during the second-half of pregnancy. DISCUSSION: Smoking women have lower and decreasing folate levels during pregnancy, possibly as a result of lower intake of these nutrients. Lower folate levels can lead to hyperhomocysteinemia, a known risk factor for several complications in pregnancy. This is an other important reason to convince pregnant women to refrain from smoking.

Validation of a knowledge based reminder system for diagnostic test ordering in general practice.

We describe the validation of a real-time automated reminder system that assists General Practitioners (GP) in appropriate test ordering. We compared the comments of human experts with the comments of the reminder system using a retrospective random selection of 253 request forms. A panel of three expert physicians judged the requested tests independently based on their interpretations of the practice guidelines. The majority assessment of the physicians was compared with the assessment of the reminder system. In case the system's output differed from the majority assessment the written practice guidelines were consulted. On average 1.75 reminders were produced per form. In total 32 of the 442 given reminders (7%) were given incorrectly. The amount of information and the level of detail (the specificity of the terms) in which the GP describes the patients' medical status are crucial for the reminder system to react correctly.

Reliability of the assessment of appropriateness of diagnostic test request behavior.

We describe the reliability of the assessment of the appropriateness of requested diagnostic tests. We used a retrospective random selection of 253 request forms with in total 1217 requested tests. Three experts made an independent assessment of each requested test. Interrater kappa values ranged from 0.33 to 0.44. The kappa values of intrarater agreement ranged from 0.65 to 0.68. The reliability coefficient for all three reviewers was 0.66. This reliability is not sufficient to make case-by-case decisions, for example to give individual feedback on the appropriateness of requested tests. Sixteen reviewers are necessary to obtain a reference with a reliability of 0.95.

Construction of an algorithm for quick detection of patients with low bone mineral density and its applicability in daily general practice.

OBJECTIVE: To construct a quick algorithm to detect patients with low bone mineral density (BMD) and osteoporosis and determine its applicability in daily general practice. DESIGN: Cross-sectional study in all 9107 postmenopausal women, aged 50-80, registered at 12 general practice centers. SUBJECTS AND MEASUREMENTS: All healthy women (5303) and 25% of the remaining group (943/3804) were invited to participate. Of 6246 invited women, 4725 (76%) participated. The women were questioned (state of health, medical history, family history, and food questionnaire) and examined [weight, height, body mass index (BMI), and BMD of the lumbar spine]. STATISTICS: Multivariable, stepwise backward and forward logistic regression analyses were performed, with BMD of the lumbar spine (L2-L4, cut-off points at 0.800 g/cm(2) for osteoporosis and 0.970 g/cm(2) for low BMD) as the dependent variable. An algorithm was constructed with those variables that correlated statistically significantly and clinically relevant with the presence of both osteoporosis and low BMD. RESULTS: The prevalence of osteoporosis was 23%, that of low BMD was 65%. Only three variables (age, BMI, and fractures) were statistically significant and clinically relevant correlated with the presence of both osteoporosis and low BMD. Age (OR 2.70 for osteoporosis and OR 1.77 for low BMD) and fractures during the past five years (OR 3.60 for osteoporosis and OR 2.85 for low BMD) were found to be the key predictors. From the algorithm the absolute risks varied from 9% to 51% for osteoporosis and from 48% to 84% for low BMD. The corresponding relative risks varied from 1.0 to 5.7 and from 1.0 to 1.8. CONCLUSIONS: Using an algorithm with age, BMI, and fracture history subgroups at high risk could be identified. However, in whatever combination, many women with osteoporosis could not be identified. Despite the differences in methods, we found predictors for osteoporosis which were comparable with the results of other cross-sectional studies, meaning that the first selection of patients at high risk for low BMD can be done adequately by both specialists and general practitioners.

Screening for osteoporosis using easily obtainable biometrical data: diagnostic accuracy of measured, self-reported and recalled BMI, and related costs of bone mineral density measurements.

The aims of the present study were: to determine the diagnostic accuracy of objectively measured, self-reported and recalled body mass index (BMI) for osteoporosis and osteopenia; to determine the diagnostic costs, in terms of bone mineral density (BMD) measurements, per osteoporotic or osteopenic patient detected, using different BMI tests; and to determine the extent to which the results can be used within the framework of the current screening program for breast cancer in The Netherlands. Within the framework of a cross-sectional study on the prevalence of osteoporosis in the south of The Netherlands, 1155 postmenopausal women aged 50-80 years were asked for their present height and their weight at age 20-30 years. Subsequently their actual weight, height and BMD of the lumbar spine (DXA) were measured. The BMD cutoff was 0.800 g/cm2 for osteoporosis and 0.970 g/cm2 for low BMD (osteoporosis + osteopenia). After receiver operating characteristic analysis, age was cut off at 60 years and BMI at 27 kg/m2. Diagnostic accuracies of objectively measured, self-reported and recalled BMI were evaluated using predictive values (PV) and odds ratios. The resulting 'true positive' and 'false positive' rates were used to calculate diagnostic costs (i.e., DXA) for each osteoporotic patient or low-BMD patient detected. The prevalence of osteoporosis in the study population was 25%, that of low BMD 65%. Only the age-BMI tests 'age > or = 60, BMI < or = 27' showed PVs for osteoporosis (31-41%) and for low BMD (71-81%) that were higher than the prior probabilities for these conditions. Related odds ratios were 2.14-3.18 (osteoporosis) and 1.87-3.04 (low BMD). The objective BMI test detected 50% of the osteoporotic patients. Using the self-reported BMI test and the recalled BMI test, detection rates increased to 55% and 69%, respectively. Concomitant costs per osteoporotic patient detected rose by 24%. Detection of patients with a low BMD increased from 38% for objective BMI and 42% for self-reported BMI to 60% for recalled BMI. Related costs increased by 11%. If all women over 50 years of age (irrespective of their BMI) were to be referred for BMD measurement, costs per osteoporotic patient or low-BMD patient detected would be 304 and 116 Euros, respectively. Only in women over 60 years does a BMI below 27 kg/m2 provide a better prediction of the presence of osteoporosis or low BMD than could be expected solely on the basis of the relevant prevalences in postmenopausal women aged 50-80 years. If the use of BMI for the detection of osteoporotic or low-BMD patients is still considered, measuring weight and just asking for a person's height will do. Although age and BMI are the strongest risk factors for osteoporosis, they are of less significance when used for screening the population for osteoporosis. More research is needed before age and BMI can be included in any screening program. As regards practical considerations alone, measurements of BMD could be implemented within the screening program for breast cancer.

Platelet factor 4 and beta-thromboglobulin in inflammatory bowel disease and giant cell arteritis.

BACKGROUND: As platelet factors are important in the inflammatory response, we examined the course of platelet factor 4 and beta-thromboglobulin in relation to disease activity in inflammatory bowel disease and in giant cell arteritis. PATIENTS AND METHODS: In a prospective study, the platelet count, platelet factor 4 and beta-thromboglobulin were measured in 20 patients with Crohn's disease, 18 with ulcerative colitis and 19 with giant cell arteritis, during active and inactive disease, as well as in 51 controls without inflammation. RESULTS: Platelet counts were significantly higher in active vs. inactive Crohn's disease, ulcerative colitis and giant cell arteritis. Levels of platelet factor 4 and beta-thromboglobulin were significantly higher in active inflammatory bowel disease and giant cell arteritis, as well as in inactive inflammatory bowel disease and giant cell arteritis, than in the non-inflammatory controls. A positive correlation was found between the Crohn's disease activity index and the platelet count, platelet factor 4 and beta-thromboglobulin. Also, a positive correlation was found between the ulcerative colitis activity index and beta-thromboglobulin. However, even after 12 months of follow-up, in Crohn's disease and ulcerative colitis the mean levels of platelet factor 4 and beta-thromboglobulin were significantly higher than the levels of the controls. CONCLUSION: Platelet factors were correlated with inflammatory bowel disease activity. Levels of platelet factor 4 and beta-thromboglobulin, however, were markedly raised for a long time in clinically inactive inflammatory bowel disease, which might point to a pre-thrombotic state of disease.

Comparing assessment of appropriateness of diagnostic tests between a human expert and an automated reminder system.

This paper describes the validation of the GRIF automated reminder system. The reminder system has been developed to influence diagnostic test ordering of General Practitioners (GPs). It generates critical comments on the basis of accepted guidelines. A retrospective random selection of 253 request forms has been taken. We compared the comments of a human expert to the comments of the reminder system. A panel of two independent reviewers judged the requested tests based on the strict interpretation of the guidelines. The sensitivity, specificity and 'predictive values' of the comments of the reminder system and the human expert were calculated using the judgement of the two reviewers as 'gold standard'.

Differential behavior of coagulation factor XIII in patients with inflammatory bowel disease and in patients with giant cell arteritis.

The aim of this prospective study was to examine the role of coagulation factor XIII (FXIII) in relation to disease activity in inflammatory bowel disease (IBD) and in giant cell arteritis. Plasma FXIII activity was studied during active and inactive disease in newly diagnosed patients with Crohn's disease (CD; n = 20), ulcerative colitis (UC; n = 18) and giant cell arteritis (GCA; n = 19), in 3-month intervals (median follow-up 12 months). FXIII was also measured in two noninflammatory control groups, age and sex matched for IBD (n = 25) and GCA (n = 26). FXIII activity was significantly lower in active CD or UC than in active GCA or the noninflammatory controls. Both in CD and UC, FXIII activity correlated inversely with indices of clinical disease activity, the erythrocyte sedimentation rate, fibrinogen and C-reactive protein levels. Low FXIII activity is a characteristic feature of active IBD, and serial measurements may be useful to assess IBD activity.

Thrombin-antithrombin III and D-dimer plasma levels in patients with benign or malignant ovarian tumours.

In 50 patients with benign ovarian tumours, 39 malignant ovarian carcinoma patients and 39 age-matched healthy women, plasma levels of thrombin-antithrombin III complex and D-dimer were determined as well as CA 125. The coagulation activation marker thrombin-antithrombin III complex and D-dimer levels were elevated in the malignant group compared to the benign and control groups. The results suggest that coagulation and fibrinolysis must play a prominent role in ovarian cancer. Moreover, D-dimer and thrombin-antithrombin III were equally useful as CA 125 for the discrimination of patients with benign or malignant ovarian tumours as evidenced by receiver operating and likelihood ratio calculations.

Human leukocyte antigen sensitization after cryopreserved human meniscal transplantations.

The presence of antibodies against human leukocyte antigens (HLA) in recipients of cryopreserved, non-tissue-antigen-matched human meniscal allografts was evaluated. Serological HLA typing was performed for both class I and class II antigens. The results showed that 11 of 18 recipients became sensitized.

The behavior of amidolytic factor VII in smoking and non-smoking pregnant women in relation to their gestational age.

OBJECTIVE: Aim of the study was to assess the behavior of factor VII by commercial amidolytic assay in smoking and non-smoking pregnant women, and to compare this with the earlier reported factor VII:C levels during pregnancy and to discuss the role of F VII:Am with regard to thromboembolic complication in smoking pregnant women. METHODS: Blood samples were obtained for 75 non-smoking pregnant women and 109 smoking pregnant women. For the chromogenic determination of F VII:Am a COA-Set F VII test kit from Kabi Vitrum was used. Correlations were calculated by the Spearman rank method. The Mann-Whitney-U test was used for the statistical comparison of the median values of the smoking and non-smoking groups. RESULTS: Both the smoking and non-smoking group displayed a significant increase of F VII:Am with gestational age (r=0.53; p<0.0001 for smokers and r=0.55; p=0.005 for non-smokers). The median concentration of F VII:Am was significantly higher in stage 3 (226%-211%) and stage 4 (262%-230%) in the smoking group. CONCLUSION: As elevated F VII:C levels have been described to be a risk factor for thrombotic events, the even higher than normally already enhanced plasma levels of FVII:Am in smoking pregnant women may indicate an additional risk for both thrombosis in the pregnant and for an increased fetal morbidity and even mortality caused by thrombotic processes in the uteroplacental vasculature. The results from the present study might be an extra argument to advise pregnant women not to smoke or to quit smoking during pregnancy.

Whole blood cell counts and leucocyte differentials in patients with benign or malignant ovarian tumours.

OBJECTIVE: The purpose of the study was to determine whether ovarian cancer patients had haematological anomalies compared to patients with benign ovarian tumours. STUDY DESIGN: Whole blood cell counts and leucocyte differentials were measured in 70 patients suspected of having ovarian tumours. Postoperatively, 20 patients had metastatic ovarian cancer and 50 patients had benign ovarian tumours. A control group consisted of 39 healthy women. Cell counting was performed by the Sysmex NE-8,000 system. The significance of differences was assessed by the Mann-Whitney U-test or the chi 2-test, where appropriate. RESULTS: The median haemoglobin and haematocrit levels were significantly lower (P-values 0.004 and 0.02, respectively) and the platelet count was higher (P = 0.02) in the malignant group compared with the benign group. The leucocyte differentials revealed significantly lower values for lymphocytes in the malignant group in comparison to the design and control groups (P-values 0.02 and 0.00005, respectively). A significant increase in monocytes (P = 0.002) and decreases in eosinophils and basophils (P-values 0.04 and 0.02, respectively) were found in the malignant group compared to the benign group. CONCLUSION: These results demonstrate significant changes in whole blood cell counts and leucocyte differentials in patients with ovarian cancer. The low lymphocyte counts in the malignant group possibly indicate a primary immunodeficiency as a casual factor.

Hemostasis in newborns of smoking and nonsmoking mothers.

OBJECTIVE: Our purpose was to determine the effect of smoking during pregnancy on neonatal hemostasis. STUDY DESIGN: Venous blood samples of 26 newborns of smoking and 25 newborns of nonsmoking mothers were obtained from the clamped umbilical cord immediately after birth. Prothrombin fragment 1+2, thrombin-antithrombin III complex, plasmin-alpha2-antiplasmin complex, and D-dimer levels were determined to assess activation of coagulation and fibrinolysis. Cotinine was measured in all neonates to objectify cigarette smoke exposure. The Mann-Whitney U test was used to compare the differences between the values of the parameters of coagulation and fibrinolysis in the two groups at the p < 0.05 level. RESULTS: The median values of prothrombin fragment 1+2 and thrombin-antithrombin III complex in newborns exposed to tobacco smoke in utero did not differ from values of newborns who were not exposed. Nor were the markers of fibrinolysis, plasmin-alpha2-antiplasmin complex and D-dimer levels, influenced by tobacco smoke exposure. CONCLUSION: The balance between the components of coagulation and fibrinolytic pathways in neonates is not disturbed by maternal smoking.

Coagulation and fibrinolysis activation markers in prostatic carcinoma patients.

In 49 patients with benign prostatic hyperplasia, 24 metastatic prostatic carcinoma patients all under palliative hormonal treatment, 17 untreated prostatic carcinoma patients without metastases and 14 untreated prostatic carcinoma patients with metastases, plasma levels of thrombin-antithrombin III complex, D-dimer and plasmin-alpha2-antiplasmin were determined. The coagulation activation marker thrombin-antithrombin III complex did not show any significant difference between the different patient groups. Of the fibrinolysis markers, D-dimer levels were elevated in both metastatic groups compared to the non-metastatic group and the benign prostatic hyperplasia group. Surprisingly, the levels of the other fibrinolysis marker, plasmin-alpha2-antiplasmin, showed no significant difference. The nature of these findings is discussed and related to other relevant literature. The general conclusion is that fibrinolysis may not play such a prominent role in prostatic carcinoma as described and expected.

Coagulation factor XIII in pregnant smokers and non-smokers.

Human blood coagulation factor XIII is a transglutaminase zymogen. Two forms exist, an extracellular or plasma factor XIII and an intracellular form. Factor XIII occurs in platelets, blood, monocytes, megakaryocytes, the liver, the placenta, and the uterus. In obstetrics, factor XIII deficiency has been associated with fetal wastage. The interaction of smoking and the quantity of coagulation factor XIII during normal pregnancy was examined in 75 non-smoking and 118 smoking (> or = 20 cigarettes/day) women. A group of subjectively healthy, non-smoking, age-matched females served as a control group (n = 30). Smokers had a higher plasma concentration of factor XIII than non-smokers. Factor XIII declined during normal gestation. During the second half of gestation the plasma concentration of factor XIII was significantly higher in smokers than in non-smokers. In smokers the decline of factor XIII was less, possibly due to platelet activation and a relative polycythemia. The later decline of factor XIII in pregnant smokers remains unexplained. More extensive research with larger patient numbers is needed to address this matter.

Haematological variables in prostatic carcinoma patients.

Routine laboratory tests of the red, white and platelet blood cell systems were performed in 49 patients with benign prostatic hyperplasia (BPH), in 24 hormonally treated patients with metastatic prostatic carcinoma, in 17 patients with untreated prostatic carcinoma without metastases and in 14 patients with untreated metastatic prostatic carcinoma. Significantly lower erythrocyte counts, haemoglobin levels and haematocrit values were found in the hormonally treated cancer group compared to all three other groups. The untreated metastatic cancer group had significantly lower haemoglobin levels and haematocrit values compared to the untreated non-metastatic cancer group. These results indicate that patients with metastases were developing anaemia and that this development was not influenced by palliative hormonal therapy. The results of this study showed that abnormal platelet counts in patients with prostatic carcinoma were rare and that the white blood cell system did not seem to be affected in patients with prostatic carcinoma.

Coagulation and fibrinolysis in smoking and nonsmoking pregnant women.

OBJECTIVES: To assess the effects of smoking during pregnancy on coagulation and fibrinolysis. DESIGN: A cross-sectional study. SETTING: A teaching hospital in Heerlen, The Netherlands. RESULTS: Parameters of coagulation activation increased significantly with gestational age. The values presented are median values. Prothrombin fragment 1 + 2 increased from 0.8 to 2.5 nmol/l in the nonsmoking group of pregnant women and from 1.0 to 1.8 nmol/l in the smoking group. Thrombin-antithrombin III (TAT) levels increased from 2.2 to 9.9 micrograms/l in the nonsmoking group and from 3.1 to 8.5 micrograms/l in the smoking group. Parameters of fibrinolysis showed a different picture. Plasminogen levels in both groups rose significantly in the first half of gestation reaching a plateau in the second half. The alpha 2-antiplasmin levels remained constant in both groups, although the smokers started with significantly higher levels: 119 versus 105% in the nonsmokers. The D-dimer levels rose significantly in both groups: from 278 to 847 micrograms/ml in the nonsmokers and from 215 to 520 micrograms/ml in the smokers. They were significantly lower in the smoking group from the 11th up to the 40th weeks. The D-dimer/TAT ratio was significantly higher in the nonsmokers. CONCLUSIONS: In smoking pregnant women the activated coagulation process was not counter balanced by an adequate increase of fibrinolysis which was the case in the nonsmokers.