Changes in liver graft rejections over time.

Incidence and possible risk factors of acute rejection, time to acute rejection, graft rejection within 3 months, multiple rejections within 1 year, steroid-resistant rejection, and graft lost to chronic rejection or to chronic dysfunction were evaluated in 388 liver transplantations. HLA matches, anti-HLA class I antibodies, positive crossmatch test, or positive cytomegalovirus serology did not have an effect on the occurrence of acute or chronic rejection. Increased total bleeding diminished occurrence of acute rejection, lengthened the time to acute rejection, and reduced the risk of steroid-resistant rejection. Immunological pretransplant factors did not have a major effect on the occurrence of rejection after liver transplantation. Different types of rejections diminished over time and the time period to the first acute rejection increased, although the basic immunosuppression stayed mainly the same over 20 years in our center.

Risk factors predicting survival of liver transplantation.

Prognostic models were developed for analyzing graft survival in a single-center study consisting of all 388 adult liver transplantations performed during 20 years. Proportional hazard models and generalized linear models were used to assess which risk factors, related to donor and recipient characteristics as well as graft preservation and operation, had an effect on graft survival. The prognostic modeling evidenced favorable trends in graft survival time during the successive quinquennials 1982-1987, 1988-1992, and 1993-1997, in comparison to the referent time period 1998-2002. Significant predictors of graft survival time were donor's age, recipient-donor gender compatibility, recipient's blood group, intraoperative blood transfusion, size of the transplanted organ, and indication for transplantation. Conventional histocompatibility matching did not correlate with graft outcome.

CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor.

Induction of a polycyclic aromatic hydrocarbon-metabolizing cytochrome P450 isoform CYP1A1 is regulated by aromatic hydrocarbon receptor (AHR). High inducibility of CYP1A1, possibly due to genetic polymorphisms, has been considered to be a risk factor for lung cancer in tobacco smokers. The relationship between low or high pulmonary expression of CYP1A1 and polymorphic genotypes of CYP1A1 and AHR was investigated in 73 active smokers. CYP1A1 expression was determined in surgical lung samples by measuring ethoxyresorufin O-deethylase (EROD) activity and by immunostaining for CYP1A1 protein. The most common allelic variants of CYP1A1 and AHR in Finns, i.e. the MspI variant (CYP1A1*2A), I462V variant (CYP1A1*2B), and -459C to T variant of CYP1A1 and the R554K variant (AHR*2) of AHR were studied using polymerase chain reaction based methods. EROD activity correlated positively with the daily cigarette consumption (r = 0.45). There was additional variation in EROD activity independent of the amount of smoking e.g. among those who smoked one pack per day until the day of operation, EROD activity ranged from 4-142 (median 48) pmol/min/mg. The frequencies of the MspI, 462V, and -459T variant alleles of CYP1A1 and 554K variant allele of AHR were 0.158, 0.055, 0.055 and 0.075, respectively. No differences were observed in the frequencies of polymorphic genotypes between the smokers with low and those with high expression, when the relationship was studied using a regression analysis adjusted for cigarette consumption. Our results thus indicate that the interindividual variation of CYP1A1 levels in smokers' lung tissue is not attributable to genetic polymorphisms of CYP1A1 or AHR tested in this study.

Mortality from occupational exposure to environmental tobacco smoke in Finland.

This article aimed to estimate the mortality from exposure to passive smoking at work in Finland. The estimation used statistics on causes of death, exposure prevalences, and risk ratios from epidemiologic studies. The attributable fractions of cause-specific mortality from passive smoking at work were 2.8% for lung cancer, 1.1% for chronic obstructive pulmonary disease, 4.5% for asthma, 3.4% for ischemic heart disease, and 9.4% for cerebrovascular stroke. Altogether, about 250 fatalities were estimated to have occurred in 1996. This is approximately 0.9% of the total mortality in the Finnish population in the relevant disease and age categories. The magnitude of mortality related to past occupational exposure to passive smoking is considerable. Preventive measures to reduce environmental tobacco smoke in the workplace will be a powerful means of reducing the high burden of respiratory and cardiovascular diseases.

Epidemiologic estimate of the proportion of fatalities related to occupational factors in Finland.

OBJECTIVES: This study attempts to estimate the proportion of annual deaths related to occupational factors in Finland and considers related methodological issues and associated uncertainties. METHODS: Statistics on causes of death, numbers of subjects exposed, and risk ratios obtained from the epidemiologic literature were used to estimate the population attributable fraction and disease burden for causes of death from work-related diseases. Gender-, age- and disease-specific numbers of deaths were provided by Statistics Finland for 1996. Information on the size of the population, broken down by gender, age, occupation, and industry, was acquired from population censuses. A Finnish job-exposure matrix supplied data on the prevalence of exposure for specific agents and the level of exposure among exposed workers. RESULTS: The attributable fraction of work-related mortality in the relevant disease and age categories was estimated to be 7% (10% for men and 2% for women), and for all diseases and ages the fraction was 4%. For the main cause-of-death categories, the attributable fraction became 12% for circulatory system diseases, 8% for malignant neoplasms, 4% for respiratory system diseases, 4% for mental disorders, 3% for nervous system diseases, and 3% for accidents and violence. The following estimates were obtained for specific important diseases: 24% for lung cancer, 17% for ischemic heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke. Based on these fractions, the total number of work-related deaths that occurred in Finland in 1996 was calculated to be on the order of 1800 (employed work force of 2.1 million); 86% involved men. CONCLUSIONS: High-quality epidemiologic studies and national survey data are essential for obtaining reliable estimates of the proportion of deaths attributable to occupational factors. The magnitude of work-related mortality is an insufficiently recognized contributor to total mortality in Finland, especially from circulatory diseases and other diseases caused by exposure to agents other than asbestos.

Cyclosporine induces myocardial connective tissue growth factor in spontaneously hypertensive rats on high-sodium diet.

BACKGROUND: The introduction of cyclosporine (CsA) has led to an improvement in the prognosis of solid organ transplantation. However, drug-induced hypertension and nephrotoxicity, associated with the development of atherosclerosis and coronary heart disease, still worsen the long-term outcome of CsA-treated patients. Whether the CsA-induced myocardial changes are associated with the induction of connective tissue growth factor (CTGF), a recently found polypeptide implicated in extracellular matrix synthesis, is not known. METHODS: Spontaneously hypertensive rats (8-9 weeks old) were treated with CsA (5 mg x kg(-1) x d(-1) subcutaneously) for 6 weeks. The influence of angiotensin-converting enzyme inhibition (enalapril 30 mg x kg(-1) x d(-1) orally) and angiotensin-1 receptor blockade (valsartan 3 and 30 mg x kg(-1) x d(-1) orally) on CsA toxicity was also investigated. Myocardial morphology was examined, and vascular lesions were scored. Localization and the quantitative expression of CTGF, as well as collagen I and collagen III, mRNA were evaluated by in situ hybridization and Northern blot. RESULTS: CsA-induced hypertension and nephrotoxicity were associated with myocardial infarcts and vasculopathy of the coronary arteries. CsA increased myocardial CTGF, collagen I, and collagen III mRNA expressions by 91%, 198%, and 151%, respectively. CTGF mRNA expression colocalized with the myocardial lesions. Blockade of the renin-angiotensin system prevented vascular damage and the CsA-induced CTGF, collagen I, and collagen III mRNA overexpressions in the heart. CONCLUSIONS: CsA increases CTGF, collagen I, and collagen III mRNA expressions in the heart. The induction of CTGF gene is mediated, at least in part, by angiotensin II.

Vascular changes in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.

Functional and morphological changes of blood vessels in cyclosporine A (CsA)-induced hypertension and nephrotoxicity were studied in spontaneously hypertensive rats (SHR). The role of the L-arginine-nitric oxide (NO) pathway and the importance of oxidative stress in CsA toxicity were also assessed. SHR (7-8 week old) on a high-sodium diet were treated with CsA (5 mg kg(-1) d(-1) s.c.) for 6 weeks. A proportion of the rats were treated concomitantly with the NO precursor L-arginine (1.7 g kg(-1)d(-1) p.o.). CsA elevated blood pressure and caused renal dysfunction and morphological nephrotoxicity. CsA also impaired mesenteric and renal arterial function and caused structural damage to intrarenal and extrarenal small arteries and arterioles. Medial atrophy of the mesenteric resistance vessels and decreased viability of smooth muscle cells of the thoracic aorta were observed. Renal and arterial damage was associated with the presence of inflammatory cells. CsA did not affect markers of the L-arginine-NO pathway (urinary cyclic GMP excretion or endothelial or inducible NO synthase expression in kidney, aorta or heart) or oxidative stress (urinary excretion of 8-isoprostaglandin F2alpha, plasma urate concentration or total radical trapping capacity). Concomitant L-arginine treatment did not affect CsA-induced changes in blood pressure or histological findings but tended to alleviate the arterial dysfunction. The renal and cardiovascular toxicity of CsA was associated with arterial dysfunction and morphological changes in small arteries and arterioles in SHR on a high-sodium diet. The findings did not support the role of oxidative stress or a defect in the L-arginine-NO pathway.

Long-term intake of milk peptides attenuates development of hypertension in spontaneously hypertensive rats.

Effect of long-term intake of isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), or a sour milk product containing these peptides on development of hypertension was investigated in spontaneously hypertensive rats (SHR). Six-week-old SHR were given: 1) water (control group), 2) IPP and VPP dissolved in water (peptide group) or 3) sour milk containing IPP and VPP (sour milk group) for 12 weeks. Systolic blood pressure (SBP) was measured by tail-cuff method. Development of hypertension was attenuated in the groups receiving tripeptides or sour milk as compared to the control group. At the end of treatment period, SBP was 176 +/- 1 mmHg in sour milk group, 181 +/- 2 mmHg in peptide group, and 193 +/- 1 mmHg in control group (P < 0.001). After treatment withdrawal, SBP rose gradually reaching the level of control group within four weeks' follow-up. In functional bioassay of ACE inhibitory activity, effect of the tripeptides on angiotensin I or angiotensin II-induced contraction in rat mesenteric arteries was evaluated. IPP inhibited the angiotensin I-induced contraction, whereas the angiotensin II-induced contraction remained unaltered. In conclusion, long-term intake of IPP and VPP, or a sour milk containing these tripeptides attenuated the development of hypertension in SHR. One possible mechanism underlying this effect is ACE inhibition.

Midazolam 12 mg is moderately counteracted by 250 mg caffeine in man.

OBJECTIVE: Caffeine (Caf) counteracts various effects of benzodiazepines (BZDs). Since the effects of zolpidem, a short-acting atypical GABA(A)-BZD agonist, were not antagonized by Caf, we studied an interaction between Caf and midazolam (Mid) in healthy volunteers. SUBJECTS, MATERIALS AND METHODS: In Study 1, 108 healthy students divided to 6 parallel groups were given Mid 12 mg (capsule) and Caf 125 and 250 mg (in decaffeinated coffee), alone and in combinations in the double-blind placebo-controlled manner. Objective and subjective tests were done before and at 45 and 90 min after intake. Ranked delta-values (changes from baseline) were analyzed by one-way contrast ANOVA and Scheffe's tests. In Study 2, six healthy subjects took Mid 15 mg (tablet) with and without Caf 300 mg. The dynamic effects were analyzed as in Study 1 and the plasma concentrations were assayed. RESULTS: In Study 1, learn effects after placebo (ad + 15%) were seen for letter cancellation and digit symbol substitution tests. Midazolam alone significantly (p < 0.05 vs. delta-placebo) reduced letter cancellation and digit symbol substitution, lowered flicker fusion, impaired digit learning and caused subjective calmness on VAS. Caffeine alone did not differ from placebo objectively, yet improved quick-wittedness and contentedness on VAS. In the combinations, Mid + Caf 125 mg differed from placebo objectively as Mid alone, whereas Mid + Caf 250 mg did not. Mid + Caf 250 mg differed from Mid on digit substitution, but did not differ from Mid+Caf 150 mg in impairing memory and causing subjective sedation. In Study 2, Mid 15 mg caused sedation and Caf 300 mg increased plasma Mid at 45 min. Mid + Caf did not differ from Mid alone objectively, but did so subjectively on VAS (p > 0.05). CONCLUSION: In conclusion, in a parallel group study, sedative effects of Mid 12 mg were only moderately antagonized by Caf 250 mg but not by Caf 125 mg. In a cross-over study, a weak interaction was found subjectively but not in objective measures.

Paternal exposure to lead and infertility.

To assess whether paternal exposure to lead is associated with infertility, we performed a register-based study among married men biologically monitored for exposure to inorganic lead. We obtained information about the marriages and the wives of the men from the Finnish Central Population Register. Data on pregnancies were obtained from medical records. Paternal exposure to lead was assessed on the basis of blood lead measurements. We estimated the risk of infertility, defined as nonoccurrence of a marital pregnancy, by applying binomial regression. For the blood lead categories of 0.5-0.9, 1.0-1.4, 1.5-1.9, 2.0-2.4, and > or =2.5 micromol/L the relative risk of infertility, compared with the risk in the lowest exposure category (<0.5 micromol/L), was 1.27 (95% confidence interval 1.08-1.51), 1.35 (1.12-1.63), 1.37 (1.08-1.72), 1.50 (1.08-2.02), and 1.90 (1.30-2.59), respectively. The findings support the hypothesis that paternal exposure to lead increases the risk of infertility at low occupational exposure levels. We applied proportional hazards regression to the analysis of pregnancy delay. A delay was observed among the wives of men exposed to lead. Exposure to lead was not clearly associated with delayed pregnancy, however, when the analysis was restricted to couples with at least one pregnancy. This finding suggests that the restriction of the study on time to pregnancy to fertile couples may introduce a bias toward no association.

Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.

1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR.

Enalapril and valsartan improve cyclosporine A-induced vascular dysfunction in spontaneously hypertensive rats.

Cyclosporine A causes hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). In the present study, arterial function was investigated using in vitro vascular preparations after long-term treatment with cyclosporine A. SHR received cyclosporine A (5 mg kg(-1) day(-1) s.c.) and high-Na(+) diet for 6 weeks during the developmental phase of hypertension. Part of the rats were treated concomitantly either with the angiotensin converting enzyme inhibitor enalapril (30 mg kg(-1) day(-1) p.o.) or with an angiotensin AT(1) receptor antagonist valsartan (3 or 30 mg kg(-1) day(-1) p.o.). In renal arteries, contractile responses to noradrenaline and angiotensin II, as well as relaxation responses to acetylcholine (endothelium-dependent) and to sodium nitroprusside (endothelium-independent), were severely impaired by cyclosporine A-treatment. There was also a trend for the dysfunction of the mesenteric arteries, but the impairment did not reach statistical difference. Enalapril and valsartan improved the impaired renal arterial functions. Cyclosporine A-induced hypertension and nephrotoxicity seem to be associated with renal arterial dysfunction in SHR on high-Na(+) diet. Antagonism of the renin-angiotensin system protects from vascular toxicity of cyclosporine A.

Modelling the reproducibility of acoustic rhinometry.

This paper presents an application of a linear model with correlated errors to the assessment of the precision of acoustic rhinometry in clinical medicine. The design of the reproducibility study involved 20 healthy subjects measured by five investigators with three replicate measurements of four variates taken from the right and left nasal cavities, altogether 2400 measurements. The parametric model may be structured to account for random variation between subjects, serial correlation within subjects and measurement error. The model-based reproducibility correlation coefficient was estimated to be fair both for the nasal volume measurements and for the nasal minimal cross-sectional area measurements with an overall average of 0.65. An alternative measure, the within-subject coefficient of variation, averaged 15 per cent. The choice between the measures of reproducibility depends on the degree of heterogeneity of the studied populations, the presence of time trend and the scale of measurement of the rhinometric variates. In clinical practice, repeated measurements should always be made to attain a reasonable level of reproducibility in acoustic rhinometry.

Alpha-lactorphin lowers blood pressure measured by radiotelemetry in normotensive and spontaneously hypertensive rats.

Cardiovascular effects of subcutaneous administration of synthetic alpha-lactorphin, a tetrapeptide (Tyr-Gly-Leu-Phe) originally derived from milk alpha-lactalbumin, were studied in conscious spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY) with continuous radiotelemetric monitoring. Alpha-lactorphin dose-dependently lowered blood pressure (BP) without affecting heart rate in SHR and WKY. The lowest dose which reduced BP was 10 microg/kg, and the maximal reductions in systolic and diastolic BP (by 23+/-4 and 17+/-4 mm Hg, respectively) were observed at 100 microg/kg dose in SHR. No further reductions were obtained at a higher dose of 1 mg/kg. There were no significant differences in the BP responses to alpha-lactorphin between SHR and WKY. Naloxone (1 and 3 mg/kg s.c.), a specific opioid receptor antagonist, abolished the alpha-lactorphin-induced reduction in BP and reversed it into a pressor response, which provides evidence for an involvement of opioid receptors in the depressor action of the tetrapeptide.

Role of endothelium and nitric oxide in experimental hypertension.

A short review on the role of endothelium and nitric oxide (NO) in experimental hypertension is presented in the light of the literature and our own recent findings. Based on these data, it is concluded that even though there is a lot of evidence in favor of the primary and causal association of endothelial dysfunction and NO in experimental hypertension, it seems still more plausible that they are causative in some types of hypertension only. Our own experience rather speaks for a secondary but still an important participation of endothelium in the maintenance and further elevation of high blood pressure. Endothelium plays a key role in the development of organ damages in hypertension.

Growth parameters in the epiphyseal cartilage of brachymorphic (bm/bm) mice.

We studied kinetics in the epiphyseal cartilage of the brachymorphic (bm/bm) mouse, combining morphometry and labeling with halogenated nucleotides. The defective synthesis of the sulfate donor PAPS in these homozygous mutants is evident in tissues with a large production of glycosaminoglycans; these compounds become undersulfated. Compared with their heterozygous siblings, the longitudinal growth of the mutant mice was reduced by two-thirds. This was mainly associated with (1) reduced height of the proliferating zone, (2) a substantial number of G0 cells in this zone, and (3) reduced hypertrophy which, in turn, may be related to premature mineralization and prevention of normal expansion of cells. No significant effects on cell-cycle parameters were detected, such as S-phase time or cell-cycle time, and the rate at which each cell increased the matrix volume seemed normal. An effect on matrix mineralization may be related to known changes in the structure of matrix PGs, whereas the effect on proliferation may be related to other factors. Candidates for such other effects of undersulfation are the cell surface PGs, which are important for binding of growth factors.

Role of arginine, taurine and homocysteine in cardiovascular diseases.

Arginine, taurine and homocysteine are amino acids which have been shown to affect the risk factors of cardiovascular diseases in humans. Arginine and taurine may protect against cardiovascular diseases while homocysteine may be a risk factor for them. Both arginine and taurine seem to lower blood pressure, arginine may also inhibit atherogenesis, and taurine may have antioxidant properties. However, the evidence of the beneficial effects of arginine and taurine supplementation from human studies is insufficient. Elevated levels of plasma homocysteine may be associated with atherosclerotic and thromboembolic cardiovascular diseases. Supplementation with folic acid seems to be effective in reducing hyperhomocysteinaemia, but there is an insufficient number of studies showing that lowering of homocysteine levels with vitamin supplementation will reduce the risk of cardiovascular diseases. In conclusion, further research is needed to determine the optimal levels for taurine and arginine in the human diet in order to decrease the risk factors for cardiovascular diseases, and to whom supplementation with folic acid should possibly be recommended to reduce hyperhomocysteinaemia. Even though the use of arginine and taurine supplements to reduce cardiovascular risk factors is an interesting possibility, the reported health-promoting effects and the safety of such a supplementation should first be confirmed.

Coffee, caffeine and blood pressure: a critical review.

OBJECTIVE: We review the published data relating to intake of coffee and caffeine on blood pressure in man. We also refer to studies on the possible mechanisms of actions of these effects of caffeine. DESIGN: The MEDLINE and Current Contents databases were searched from 1966 to April 1999 using the text words 'coffee or caffeine' and 'blood pressure or hypertension'. Controlled clinical and epidemiologic studies on the blood pressure effects of coffee or caffeine are reviewed. We also refer to studies on the possible mechanisms of action of these effects of caffeine. RESULTS: Acute intake of coffee and caffeine increases blood pressure. Caffeine is probably the main active component in coffee. The pressor response is strongest in hypertensive subjects. Some studies with repeated administration of caffeine showed a persistent pressor effect, whereas in others chronic caffeine ingestion did not increase blood pressure. Epidemiologic studies have produced contradictory findings regarding the association between blood pressure and coffee consumption. During regular use tolerance to the cardiovascular responses develops in some people, and therefore no systematic elevation of blood pressure in long-term and in population studies can be shown. CONCLUSIONS: We conclude that regular coffee may be harmful to some hypertension-prone subjects. The hemodynamic effects of chronic coffee and caffeine consumption have not been sufficiently studied. The possible mechanisms of the cardiovascular effects of caffeine include the blocking of adenosine receptors and the inhibition of phosphodiesterases.

Methodologic issues in epidemiologic risk assessment.

This paper reviews methodologic issues pertinent to the application of epidemiology in risk assessment and discusses concerns in the presentation of results from such an activity. Assessment of the health risks associated with occupational and environmental exposures involves four phases: hazard identification, i.e., the detection of the potential for agents to cause adverse health effects in exposed populations; exposure assessment, i.e., the quantification of exposures and the estimation of the characteristics and sizes of the exposed populations; dose-response assessment, i.e., the modeling for risk realization; and risk characterization, i.e., the evaluation of the impact of a change in exposure levels on public health effects. The risk-assessment process involves limitations of exposure data, many assumptions, and subjective choices that need to be considered when using this approach to provide guidance for health policy or action. In view of these uncertainties, we suggest that the provision of estimates of individual risk and disease burden in a population must be accompanied by the corresponding estimates of precision; risks should be presented in a sufficiently disaggregated form so that population heterogeneities are not lost in the data aggregation; and different scenarios and risk models should be applied. The methods are illustrated by an assessment on the health impacts of exposure to silica.

Haemolytic-uraemic syndrome caused by vero toxin-producing Escherichia coli serotype Rough: K-: H49.

The first case of haemolytic-uraemic syndrome (HUS) caused by Vero toxin-producing Escherichia coli (VTEC) which belonged to a novel serotype, Rough: K-: H49, is reported. The case was initially diagnosed as nephropathia epidemica caused by Puumala virus, but the subsequent diagnosis of HUS caused by VTEC was made after bacteriological investigation. The strain isolated fermented sorbitol produced VT2 toxin but not enterohaemolysin, nor did it carry the eaeA gene. In VTEC strains, the O antigen, the eaeA gene and enterohaemolysin production have been characterized as virulence-associated factors and believed to have an effect on pathogenesis of these strains to cause haemorrhagic colitis or HUS. The findings of this study demonstrate that there is a need for further studies to evaluate the pathogenetic mechanism of VTEC and need for easy diagnostic methods exploiting other properties than O157 antigen and non-fermentation of sorbitol to find all VTEC in human infections.