Impact of migration on diabetes burden: audit in the metropolitan area of Bologna, Italy.

PURPOSE: To investigate the impact of diabetes in immigrants on the Italian healthcare system, as well as their compliance with standard protocols of control and treatment. METHODS: The prevalence of immigrants with diabetes living in the metropolitan area of Bologna (about 1 million inhabitants) in 2019 was investigated using a database containing all subjects in active follow-up for diabetes, based on antidiabetic drug use, disease-specific copayment exemption, ICD-9 codes, continuous care in diabetes units. Country of origin was derived from fiscal code. RESULTS: The overall prevalence of diabetes (n = 53,941; 51.8% males, median age 64) was 6.1% in both Italy-born and immigrant cohorts. Immigrant prevalence was 12.4%, moderately higher than that observed in the total population (12.2%). Diabetes risk was increased in the whole immigrant cohort (odds ratio (OR) 1.74; 95% Confidence Interval (CI) 1.69-1.79). Among cases with incident diabetes, the proportion of immigrants (median age, 49 vs. 65 in Italy-born individuals) increased progressively from 11.7% to 26.5% from 2011 to 2019 (males, 8.9-21.0%; females, 14.9-32.8%) in all age groups, particularly in young adults, but also in older subjects. Metabolic control was lower in immigrants, as was adherence to shared diagnostic and therapeutic protocols, without systematic differences in antidiabetic drug use, but much lower use of drugs for comorbid conditions. CONCLUSIONS: The population with diabetes in the metropolitan area of Bologna is rapidly changing. Quality improvement initiatives are needed to reduce the burden for the universalistic Italian health care system generated by the rapidly-growing high-risk immigrant population.

A comparison of risk factors as predictors of cardiovascular and non-cardiovascular mortality in the elderly people--relevance of N-terminal pro-B-type natriuretic peptide and low systolic blood pressure.

BACKGROUND: Many risk factors are known to predict ischaemic events and mortality in the elderly people, but their ranking of importance remains uncertain. This study was designed to identify and compare the main predictors of total mortality (TM), cardiovascular mortality (CVM) and non-cardiovascular mortality (NCVM) in older adults. METHODS: Nine hundred and seventy-nine community resident adults aged ≥ 65 years, free of previous heart failure and cardiovascular events, participated in the study. The univariate and multivariate (Cox regression) relationships of baseline cardiovascular risk factors, treatments and laboratory data with TM, CVM and NCVM were assessed after a median follow up of 6.7 years. RESULTS: Overall, there were 104 deaths (30 because of CVM and 74 to NCVM). In multivariate analysis, the following factors remained independently associated with mortality: NT pro-B-type natriuretic peptide (NT-proBNP) upper quintile (≥ 237 pg/ml for men, ≥ 280 pg/ml for women): hazard ratio (HR) vs. the rest of the population (95% confidence interval) 2.34 (1.52-3.60), p < 0.001 for TM; HR 5.41 (2.32-12.65), p < 0.001 for CVM; systolic blood pressure lower quintile (≤ 130 mmHg): HR 3.06 (1.80-5.21), p < 0.001 for NCVM; diabetes: HR 2.46 (1.29-4.72), p = 0.007 for NCVM; erythrocyte sedimentation rate (ESR) upper decile (≥ 41 mm/h): HR 2.33 (1.16-4.69), p = 0.02 for NCVM; platelet count lower quintile (≤ 177 × 10(9) /l): HR 2.09 (1.20-3.64), p = 0.009 for NCVM; ever-smoker status: HR 2.08 (1.23-3.52), p = 0.007 for NCVM. CONCLUSIONS: In elderly community dwellers, NT-proBNP was the strongest predictor of TM and CVM, while especially low systolic blood pressure, together with diabetes, ESR, reduced platelet count and ever-smoker status, were the main predictors of NCVM.

Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression.

BACKGROUND: In prostate adenocarcinoma, the dissection of the expression behaviour of the eukaryotic elongation factors (eEF1A1/2) has not yet fully elucidated. METHODS: The EEF1A1/A2 expressions were investigated by real-time PCR, western blotting (cytoplasmic and cytoskeletal/nuclear-enriched fractions) and immunofluorescence in the androgen-responsive LNCaP and the non-responsive DU-145 and PC-3 cells, displaying a low, moderate and high aggressive phenotype, respectively. Targeted experiments were also conducted in the androgen-responsive 22Rv1, a cell line marking the progression towards androgen-refractory tumour. The non-tumourigenic prostate PZHPV-7 cell line was the control. RESULTS: Compared with PZHPV-7, cancer cells showed no major variations in EEF1A1 mRNA; eEF1A1 protein increased only in cytoskeletal/nuclear fraction. On the contrary, a significant rise of EEF1A2 mRNA and protein were found, with the highest levels detected in LNCaP. Eukaryotic elongation factor 1A2 immunostaining confirmed the western blotting results. Pilot evaluation in archive prostate tissues showed the presence of EEF1A2 mRNA in near all neoplastic and perineoplastic but not in normal samples or in benign adenoma; in contrast, EEF1A1 mRNA was everywhere detectable. CONCLUSION: Eukaryotic elongation factor 1A2 switch-on, observed in cultured tumour prostate cells and in human prostate tumour samples, may represent a feature of prostate cancer; in contrast, a minor involvement is assigned to EEF1A1. These observations suggest to consider EEF1A2 as a marker for prostate cell transformation and/or possibly as a hallmark of cancer progression.

Body composition and muscular strength changes after moderate activity: association with matrix metalloproteinase polymorphisms.

Remodeling of skeletal muscles is regulated by matrix metalloproteinases (MMPs). Functional genetic polymorphism (PM), modulating the expression of some MMPs, might be associated to different body composition and muscular strength improvement after exercise. Genetic PM of MMP-1 (G+/- at -1607), MMP-3 (5A/6A at -1171) and MMP-9 (Cytosine-Adenine microsatellite=(13-27)CA) repeats, around -90), body cell mass (BCM), extracellular water (ECW) and isometric maximal extensor strength (MES) of both legs were determined in 17 old sedentary women at the beginning and at the end of a 24 week physical exercise program. A 12 and 72% increase in BCM and MES, respectively, and 11% reduction in ECW were observed at the end of the program. Carriers of G-insertion in MMP-1, PM increased their BCM (7 kg vs. -1.5, p=0.007) and lost ECW (9% of total body water vs. 0.1%, p=0.004) more than the non-carriers; homozygote for 21 or less CA repeats/allele in MMP-9 PM gained more MES (115 N, interquartile range=IQR=63-132) than carriers of longer microsatellites (63 N, IQR=40-86, p=0.028). MMP-3 did not show any association with body composition and exercise-related strength changes. Exercise in elderly women increases BCM and strength, these changes are associate to specific MMP genotypes.

Use of histopathological indicators on chub (Leuciscus cephalus) and brown trout (Salmo trutta fario) in evaluating river environments.

A multidisciplinary study was conducted on water from two rivers in the Abruzzo region of Italy. The study highlighted the importance of histopathological investigations in the evaluation of the environmental impact on fish. Brown trout (Salmo trutta fario) from the Aterno river and chub (Leuciscus cephalus) from the Vomano river were sampled in winter and then again in spring. Histopathological investigations of gills, kidneys and livers revealed inflammatory and degenerative lesions, early warning signals of environmental stress. Lesions were evaluated semi-quantitatively and findings were ranked. The histopathological features were compared with results obtained from the analysis of water samples and macroinvertebrates collected in the two rivers (extended biotic index). All results confirmed alterations of the environment.

Long term prognosis in patients with peripheral arterial disease treated with antiplatelet agents.

OBJECTIVE: To determine the fatal and non-fatal cardiovascular event rate in patients with intermittent claudication treated with antiplatelet agents. METHODS AND DESIGN: Patients with PAD-II stage Fontaine (n=223) and sex and age matched controls (n=446) were followed up from 1974 to 1998. All patients were treated with antiplatelet agents (aspirin, 325 mg once daily or ticlopidine, 250 mg twice daily) and for risk factors, if present. The end points were death for any cause (vascular event, cancer, and others) and non-fatal vascular events (myocardial infarction, ischemic/hemorrhagic stroke, and leg amputation). RESULTS: PAD patients had a significantly higher mortality rate than controls (3.99 vs. 2.53 deaths for 100 patients per year, respectively), cancer (mostly lung, stomach and colon) and vascular mortality accounted for such difference. The incidence of non-fatal vascular events was three times higher in patients than in controls (1.7 vs. 0.56, 100 patients per year, respectively, p<0.05) even considering amputation separately (0.28 vs. 0.00, 100 patients per year, p<0.05). No difference between patients treated with aspirin or ticlopidine could be found in both end points. CONCLUSIONS: Vascular mortality and morbidity, despite the use of antiplatelet agents, are still higher than sex and age matched controls; however, the commonest cause of death is cancer.

Coagulation indicators in chronic stable effort angina and unstable angina: relationship with acute phase reactants and clinical outcome.

The aim of the study was to evaluate which pattern of coagulation indicators characterizes unstable angina and, particularly, its relationship with short-term prognosis. Forty patients with unstable angina (UA Group) at admission in the intensive care unit, 40 patients with chronic stable effort angina (SEA Group), and 20 age- and sex-matched healthy controls were studied. Blood coagulation indicators were fibrinogen, prothrombin fragment F1 + 2 (F1 + 2), thrombus precursor protein (TpP), and D-dimer. C reactive protein (CRP) and cardiac Troponin I (cTnI) have also been determined and compared. Patients in the UA Group were followed for in-hospital adverse events (sudden death, acute myocardial infarction and angina refractory to medical therapy). CRP, D-dimer and cTnI plasma levels were significantly lower in the SEA Group than in the UA Group; the same trend was found for fibrinogen and F1 + 2 plasma levels, although not statistically significant. The TpP was similar in all groups. The control group showed the lowest levels for all indicators. Within the UA Group, 17 patients developed adverse events during hospitalization; F1 + 2, D-dimer, cTnI and CRP plasma levels were higher in these patients than in those with good outcome. Relative risks for adverse events associated with the highest tertile of D-dimer, cTnI, and CRP plasma levels were 8.4 (95% confidence interval, 1.5-48.9), 6.7 (95% confidence interval, 1.1-38.6) and 5.2 (95% confidence interval, 1.1-25.2), respectively. D-Dimer is significantly increased in patients with unstable angina and, in particular, in those who develop an adverse event.

Coagulation indicators in patients with paroxysmal atrial fibrillation: effects of electric and pharmacologic cardioversion.

The aim of this study was to determine whether paroxysmal atrial fibrillation (PAF) and/or restoration to sinus rhythm with electric or pharmacologic cardioversion induce modifications to the coagulation system. Thirty-five patients with PAF undergoing either electric (n = 11) or pharmacologic (n = 24) cardioversion were studied. Fibrinopeptide A and D-dimer blood samples were taken immediately before and after cardioversion at different intervals. When compared with the control group (n = 70), the precardioversion fibrinopeptide A plasma values were significantly elevated (11.8 vs 2.5 ng/mL). Fibrinopeptide A plasma values were significantly reduced 5 minutes after cardioversion (11.8 vs 5.3 ng/mL) and remained stable throughout the follow-up sequential measurements. D-dimer plasma values were significantly increased (measured at 12 hours and at day 7) in patients who underwent electrical cardioversions only. A positive correlation (R(2) = 0.76) was found between the energy delivered for cardioversion to sinus rhythm and D-dimer plasma values on day 7. In patients with PAF, levels of fibrinopeptide A, an indicator of coagulation activation, are elevated and soon reduced by the restoration of sinus rhythm. Electric, but not pharmacologic, cardioversion induces an early activation of the fibrinolytic system.

Atherosclerosis and inflammation. Patterns of cytokine regulation in patients with peripheral arterial disease.

Inflammatory phenomena at sites of atherosclerotic plaques are increasingly thought to be major determinants of the progression and clinical outcome of atherosclerotic disease. Therefore, attention is being paid to systemic markers/mediators which may reflect the inflammatory activity in the plaques. This study evaluates the pattern of the main proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), their soluble receptors/antagonist, and a variety of inflammatory markers, in patients with peripheral arterial disease (PAD). Eight patients with PAD suffering from claudicatio intermittens (CI), eight with critical limb ischemia (CLI) and eight controls (C) were studied. Blood samples were collected at baseline in all groups and. for C and CI, immediately after and 4 h after a 30-min treadmill test. Baseline: no differences in cytokine plasma levels were detected among the three groups. In contrast, soluble receptors of TNF (type I and II) and of IL-6, and IL-1beta receptor antagonist (IL-1ra) were increased in CI and CLI patients, as compared to C. Of note, IL-Ira correlated with the occurrence and stage of the disease in a highly significant proportion of the patients, reaching a predictive value for the disease of P < 0.0001. The opposite trend was observed for the soluble receptor of IL-1beta. Notably, in the patients no alterations could be found in white blood cell counts, expression of CD11c adherence molecule by circulating monocytes or, in vitro. O2- release from zymosan-activated neutrophils. Moreover, plasma levels of platelet activating factor (PAF), of neutrophil elastase and of the acute phase reactants C-reactive protein (CRP) and alpha1-acid glycoprotein were not found to be significantly altered. In contrast, the acute-phase proteins alpha1-antitrypsin (alpha1AT) and haptoglobin (HG) were found to be increased. Effect of treadmill: IL-1beta and TNFalpha remained at baseline levels following exercise, and IL-6 dropped to undetectable levels. Among cytokine antagonists, again the most relevant changes concerned the IL-1ra, which was significantly increased immediately after the treadmill test, both in CI and C, and returned to baseline levels after 4 h. In contrast, soluble TNFalpha, IL-1beta and IL-6 receptors, PAF, and the other markers of leukocyte activation were not found to be altered. Soluble TNFalpha and IL-6 receptors were shown to inhibit the biological effects of their ligands. Similarly, IL-1ra and the acute phase proteins alpha1AT and HG have been reported to exert anti-inflammatory functions. The increased plasma levels of these agents, together with low levels of inflammatory cytokines and other pro-inflammatory mediators such as PAF and alpha1-acid glycoprotein, appear to draw an undescribed picture, so far, of upregulation of a composite systemic anti-inflammatory mechanism in atherosclerotic patients. IL-1ra appears to be a reliable marker of the state of activation of this mechanism. These results may provide a basis for developing new insights into the pathogenesis of the atherosclerotic disease.

Mechanisms of malnutrition in uremia.

The pathogenesis of protein wasting in chronic renal failure is multifactorial. Potential mediators of protein catabolism in chronic uremia include anorexia, low protein-energy intake, increased cortisol and parathyroid hormone secretion, insulin resistance, metabolic acidosis and unidentified uremic toxins. In non-acidotic uremic patients the rate of protein turnover (that is, synthesis and degradation) has often been found to be decreased. Malnutrition also decreases both protein synthesis and degradation. In contrast, during acidosis protein degradation is primarily accelerated and results in rapid loss of body proteins. Cytokine concentrations have often been found increased in both dialyzed and undialyzed chronically uremic patients. Our study determined the circulating levels of TNF-alpha and of type I (60 kDa) and type II (80 kDa) soluble TNF-alpha receptors in undialyzed uremic patients, and found that their plasma levels were greatly increased. Serum creatinine correlated with TNF-alpha soluble receptors but not with the TNF-alpha. Thus, TNF-alpha is potentially an important mediator of protein wasting in chronically uremic patients. Pharmacological therapy of protein catabolism in chronic uremia may include the administration of pentoxifylline, which has been shown to decrease protein degradation by interfering with the TNF-alpha system (that is, TNF-alpha and its soluble receptors) in experimental models. Growth hormone and insulin-like growth factor-1 administration may also be beneficial in these patients, but further evaluation of the hormone effects on glucose and glutamine metabolism is called for.

D-dimer and anticoagulation in patients with mechanical prosthetic heart valves. A 2-year follow-up.

The best anticoagulation level in patients with mechanical heart valve prostheses is still being debated. D-dimer, which detects the presence of cross-linked fibrin degradation products, has been demonstrated to be a useful marker of coagulation activation. This study was designed to verify whether heart valve prostheses in anticoagulated patients are associated with abnormalities in D-dimer plasma levels, and if so, whether such levels are related to the anticoagulation level and/or whether they could be predictive of acute vascular or hemorrhagic events. In 132 patients with single and 10 with double mechanical valve replacement, international normalized ratio (INR) and D-dimer plasma levels were determined. The INR levels of the previous 8 months were reviewed to assess the time that each patient spent in the therapeutic range. The D-dimer plasma levels were compared with those obtained from 102 matched control subjects. The patients were then followed up for 2 years to record acute vascular and hemorrhagic events. For the entire group, D-dimer plasma levels in patients were the same as those in the control group. Patients with double valve replacement had higher D-dimer plasma levels than either monovalvular implant patients or control subjects. Patients who had spent < 75% of the time within the assigned anticoagulation range had higher values for D-dimer plasma levels (median, 270 vs 198 ng/mL, P = .02). The major determinants of D-dimer plasma levels were age (R2 = .07, P = .009) and the percentage of time spent below the predetermined INR level (R2 = .09, P = .001). During follow-up, 19 acute vascular and 16 hemorrhagic events occurred. High D-dimer tertile was the only parameter predicting the occurrence of thromboembolic events. In patients with mechanical heart valve prostheses, the D-dimer plasma level depended on the thoroughness of anticoagulation. Patients in the upper tertile of D-dimer values have an approximately 5-fold risk of vascular thromboembolic events. D-dimer determination can therefore be useful in detecting patients who are at a higher risk of severe vascular events.

Activation of coagulation by a LDL-apheresis device.

LDL-apheresis often induces an almost constant and progressive increase of the differential pressure of plasma flowing through the dextran sulphate cellulose column, reducing the efficacy of the treatment. On two occasions we were able to identify a fibrin plug by immunofluorescence. Our aim was to verify the modification of some coagulation indicators in patients undergoing LDL-apheresis and whether an activation of coagulation occurs in the LDL-apheresis device. Blood samples were obtained from six patients with familial hypercholesterolaemia who were undergoing LDL-apheresis. During the same session further blood/ plasma samples were taken from the LDL-apheresis device at different sites and at different volumes of filtered blood. In patients after LDL-apheresis the following modifications were found: a 25% decrease of fibrinogen and a slight increase in F1 + 2 plasma levels. No relevant changes in thrombin-antithrombin complexes and fibrinopeptide A plasma levels were noted. In the LDL-apheresis device the main results were: (a) fibrinogen was trapped in the dextran sulphate cellulose column in the early phases; (b) activation of coagulation was recognisable in the plasma separator during the procedure and progressively increased with duration of LDL-apheresis; (c) thrombin-antithrombin complexes, formed in the plasma separator, were retained by the dextran sulphate cellulose column. In conclusion, LDL-apheresis activates coagulation in the device. Shortening cycle time or using nafamostat mesilate as an anticoagulant, could be interesting alternatives for improving the procedure.

Fibrinogen, D-dimer and thrombin-antithrombin complexes in a random population sample: relationships with other cardiovascular risk factors.

Fibrinogen is an independent risk factor for cardiovascular disease and both D-Dimer and Thrombin-Antithrombin complexes may be suitable as laboratory markers of deep venous thrombosis and are becoming more widespread in clinical practice. The aim of our study was to evaluate their normal range and to examine their correlation with various cardiovascular risk factors. Fibrinogen, D-Dimer and Thrombin-Antithrombin complexes were assessed in 516 normal subjects randomly selected from the National Health Service register of Trieste (Italy). In our community the mean value of fibrinogen was 283 +/- 71 mg/dl. Fibrinogen increases with age in males and was significantly higher in male smokers. In non-smokers, females had significantly higher fibrinogen values than males. The mean value of D-Dimer was 306 +/- 130 ng/ml. In females it is significantly higher. The fibrinogen and D-Dimer correlation coefficient was 0.20 (p < 0.001). The mean level of Thrombin-Antithrombin complexes was 6.25 +/- 6.8 ng/ml with a distribution markedly skewed towards the left; males had lower concentration than females (p = 0.047). Multiple regression analysis for fibrinogen as a dependent variable showed that D-Dimer, LDL-cholesterol, Body-Mass Index and Thrombin-Antithrombin complexes were poor predictors for fibrinogen plasma levels (R2 = 0.23) and that fibrinogen, ApoA1 and age can explain only about 10% of the observed variability in D-Dimer.

Psoriasis and endothelins.

BACKGROUND: Psoriasis is characterized by an abnormal proliferation and increased turnover of keratinocytes, the presence of acute and chronic inflammatory cells and microangiopathic changes. Endothelins are a family of peptides which have been investigated especially for their effects on the cardiovascular system. Recent studies have demonstrated their involvement also in human skin. AIM OF THE STUDY: We evaluated the Endothelin-1 and 2 plasma levels in psoriatic patients, as endothelin-1 can be produced in vitro by keratinocytes and can stimulate the proliferation of fibroblasts as well as modify the skin microcirculation dynamics. PATIENTS AND METHODS: We studied 30 patients: 10 affected with psoriasis (PASI from 5 to 10), 10 affected with cardiovascular diseases and 10 healthy controls. The Endothelin-1 and 2 plasma levels were evaluated by radio-immunoassay procedure. RESULTS: A significant increase in Endothelin-1 and 2 plasma levels was observed in the psoriatic patients, in comparison with the controls. CONCLUSIONS: Our data seem to suggest a possible relationship between psoriasis and increased plasma level of endothelin-1 and 2, though the possible role played in the pathogenesis of psoriasis needs further studies.

In vivo cooperation between introns during pre-mRNA processing.

In higher eukaryotes the large number of introns present in most genes implies that the pre-mRNA processing machinery should be efficient and accurate. Although this could be achieved at the level of each intron, an attractive alternative would be that interactions between introns improve the performance of this machinery. In this study we tested this hypothesis by comparing the processing of transcripts of the tumor necrosis factor beta gene, which differ only by their number of introns. We took advantage of the ordered splicing of the three introns present in this gene to design constructs that should generate, as primary transcripts, molecules that are normally produced by splicing. We established that the apparent splicing rate of intron 3 is increased 2.5- and 3.5-fold by the presence of one or two other introns on the primary transcript, respectively. Similarly, the apparent splicing rate of intron 2 is increased by the presence of intron 1. As these effects involve the splice sites of the upstream intron, these observations support the existence of cooperative interactions between introns during pre-mRNA processing.

Treatment of intermittent claudication with antiplatelet agents.

In a double-blind study, 296 patients with intermittent claudication (Fontaine stage II) were treated with 250 mg ticlopidine twice daily, 500 mg aspirin every third day plus 75 mg dipyridamole three times daily, or 300 mg xanthinol nicotinate three times daily for 6 months. Ticlopidine and aspirin/dipyridamole, but not xanthinol nicotinate, improved platelet aggregation, reduced beta-thromboglobulin, platelet factor IV and fibrinopeptide A concentrations, and increased antithrombin III concentrations and red blood cell filterability. No changes in lipid profiles, platelet count or fibrinogen were recorded following any treatment. The doppler systolic blood pressure ratio was improved in patients treated with ticlopidine or aspirin/dipyridamole, but not with xanthinol nicotinate. It is concluded that antiplatelet treatment is useful for the treatment of limb arteriopathy.

[Intravenous pentoxifylline in Fontaine stage II and III peripheral arterial diseases]. / La pentossifillina per via endovenosa nell'arteriopatia periferica al II e III stadio Fontaine.

Thirty patients with lower limb arterial disease (15 Fontaine stage II, 15 stage III) were treated for two weeks with continuous pentoxifylline infusion (1 g daily). In all cases, a significant improvement of the Winsor index was obtained: in stage II from 0.57 +/- 0.11 to 0.67 +/- 0.15 (p less than 0.008), and in stage III from 0.43 +/- 0.20 to 0.58 +/- 0.19 (p less than 0.042). In patients who could be submitted to treadmill exercise, the average distance increased from 216 +/- 88 m to 314 +/- 187 m (p less than 0.05) while distance walked without pain increased from 124 +/- 76 m to 199 +/- 153 (p less than 0.05).

Relation of haemostatic function, neurovascular impairment, and vibration exposure in workers with different stages of vibration induced white finger.

Haemostatic function and neurovascular symptoms were investigated in 67 workers exposed to vibration and 46 comparable referents. Of these 65.6% of vibration workers complained of neurological disturbances (stages 0T, 0N of Taylor's classification for vibration induced white finger (VWF) and 20.9% suffered from Raynaud's phenomenon (stages 1-2-3). The severity of the staging symptoms showed a close relation with an index of vibration dose computed on the basis of vibration measurement and individual exposure time. Indices of platelet aggregation, both in vitro and in vivo, antithrombin III, fibrinogen and fibrinopeptide A levels were not different in the exposed workers compared with the referents. No relation was found between haemostatic parameters and the severity of VWF. Exposed workers responded to a cooling procedure with a more pronounced vasoconstriction in the digital vessels than the referents, as indicated by delayed recovery time of finger skin temperature after the cold test. These findings suggest that both in the early stages (0T, 0N) and in more severe stages of VWF (stages 1-2) cold induced hyperreactivity in the digital vessels and Raynaud's syndrome are vascular disorders of functional origin occurring without any prethrombotic alterations.