[Comparison of Plaster Fixation and Kirschner Wire Transfixation as Temporary Fixation of Displaced Ankle Fractures - Randomised Prospective Study]. / Porovnání sádrové fixace a transfixace Kirschnerovými dráty pri docasné fixaci dislokovaných zlomenin hlezna ­ randomizovaná prospektivní studie.

PURPOSE OF THE STUDY The purpose of the study was to assess two therapeutic procedures of temporary fixation of displaced ankle fractures, namely the plaster fixation or Kirschner wire (KW) transfixation via the sole of the foot. MATERIAL AND METHODS Group of patients The randomised prospective study conducted in the period 02/2016-02/2017 compared two methods of temporary fixation of displaced ankle fractures. In total, 38 patients were included in the study (18 patients treated with plaster fixation, 20 patients treated with KW). Methods During the randomisation (by envelopes, drawing of lots by the patient), in one group of patients, temporary stabilisation by plaster fixation was performed, whereas the other group was treated by percutaneously inserted KWs. The attention was focused on the quality of achieved reduction, its retention until the final treatment, and soft tissue status. After one year, the final examination was performed, in which we focused on the assessment of the clinical condition of the ankle joint with the use of the Olerud-Molander Ankle Score (OMAS), the AOFAS (American Orthopedic Foot and Ankle Society) score, and the Visual Analogue Scale (VAS) measuring the overall satisfaction. Moreover, in both the methods potential incidence of arthritic changes was monitored on radiographs. RESULTS Both the methods achieved 100% successful reduction rate. The group with plaster fixation reported a loss of reduction in six patients (33.3%) as against the KW group where no loss of reduction occurred. This difference was significant (p = 0.007). In plaster fixation method, after its removal local complications occurred on skin in 56%, of which skin necrosis in 16.7%, and it always occurred in association with the loss of reduction, which was statistically significant (p = 0.245). In KW method, local complications on skin were present in 25% only. In the group of patients with KW, there was not a single case of surface or deep infection reported. No KW migration was observed. DISCUSSION Potential complications of conservative treatment of displaced fractures with plaster fixation include the migration of fragments and widening of the ankle fork during the further course which may threaten the vitality of soft tissues. A total of six patients (33.3%) treated with plaster fixation showed a failure of reduction, which is by approximately 10% more than described in literature. In seven cases after the plaster fixation removal bullae were observed (38.9%) and in three cases skin necrosis was present (16.7%), which occurred in re-displaced fractures only. The bullae were present whether the reduction was successfully maintained or not. In literature, local complications after plaster fixation removal are reported in roughly 14%. Temporary percutaneous ankle KW transfixation is applied to maintain the reduced fracture in a favourable position and to facilitate monitoring and treating the soft tissues. Prior to the final surgical solution, bullae were observedin four cases (20%), of which skin necrosis in one case (5%). Bullae formation and necrosis are most likely related to the initial damage to soft tissues due to the injury and were not caused by the KW insertion. The literature describes local complications in 7% with respect to the KW technique, however, the type of complications is not specified. In our group, at a one-year follow-up arthritic changes grade I and II according to Kellgren and Lawrence scale were reported in 70% of cases with KW technique. Whether the osteoarthritis was caused by fixation or the fracture itself and what would be the percentage of individual types of osteoarthritis after several years of follow-up is a question. CONCLUSIONS Plaster fixation or Kirschner wires for temporal fixation of displaced ankle fractures shall be applied on a case by case basis. Based on our findings, the application of plaster fixation to displaced ankle fractures does not provide adequate stability of the reduced fracture and in case of re-displacement the status of soft tissues deteriorates. The impossibility to control the status of soft tissues in plaster fixation and the lower complication rate in fixation with K wires constitute additional reasons why this fixation technique via the sole of the foot appears to reap more benefits. Key words:displaced ankle fractures, temporal fixation, plaster fixation, Kirschner wire transfixation, complications.

Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern.

OBJECTIVE: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail. DESIGN: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m(2)) and compared with GH, insulin and glucose levels. METHODS: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated. RESULTS: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels. CONCLUSIONS: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.

Effect of intestinal microfloras from vegetarians and meat eaters on the genotoxicity of 2-amino-3-methylimidazo[4,5-f]quinoline, a carcinogenic heterocyclic amine.

Aim of this study was to investigate the impact of intestinal microfloras from vegetarians and non-vegetarians on the DNA-damaging activity of 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), a carcinogenic heterocyclic amine that is found in fried meats. Floras from four vegetarians (Seventh Day Adventists) and from four individuals who consumed high amounts of meats were collected and inoculated into germfree F344 rats. The rats were kept on isocaloric diets that either contained animal derived protein and fat (meat consumers group) or proteins and fat of plant origin (vegetarian groups). IQ (90 mg/kg bw) was administered orally, after 4 h the extent of DNA-damage in colon and liver cells was determined in single cell gel electrophoresis assays. In all groups, the IQ induced DNA-migration was in the liver substantially higher than in the colon. In animals harbouring floras of vegetarians, the extent of damage was in both organs significantly (69.2% in the liver, P<0.016 and 64.7%, P<0.042 in the colon, respectively) lower than in the meat consumer groups. Our findings show that diet related differences in the microfloras have a strong impact on the genotoxic effects of IQ and suggest that heterocyclic amines are less genotoxic and carcinogenic in individuals that consume mainly plant derived foods.

Validation of a mathematical model predicting the response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency.

OBJECTIVE: To validate a mathematical model developed by Ranke et al. (J Clin Endocrinol Metab 1999;84:1174-7783) to predict the GH response during the first years of GH replacement therapy. PATIENTS AND METHODS: 38 children with idiopathic GH deficiency (GHD) met all inclusion criteria for the prediction model, but the group differed in some characteristics from the cohort from which the model was derived. RESULTS: Using the model for the 1st year including maximum GH after stimulation and the equation for the 6th year, the predicted value corresponded well with actual height gain. Differences were found when the growth response of the 1st year excluding maximum GH and that of the 2nd-5th year were calculated, resulting in a significant underestimation of actual height gain (-0.63 to -1.07 cm/year). CONCLUSION: The mathematical prediction model tended to underpredict the growth response to GH treatment in our patients with pronounced GHD. The severity of GHD seems to be an important parameter for the 1st year prediction.

Association of microsomal epoxide hydrolase polymorphisms and lung cancer risk.

Microsomal epoxide hydrolase (mEH) plays a dual role in the detoxification and activation of tobacco procarcinogens. Two polymorphisms affecting enzyme activity have been described in the exons 3 and 4 of the mEH gene, which result in the substitution of amino acids histidine to tyrosine at residue 113, and arginine to histidine at residue 139, respectively. We performed a hospital-based case-control study consisting of 277 newly diagnosed lung cancer patients and 496 control subjects to investigate a possible association between these two polymorphisms and lung cancer risk. The polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism and TaqMan assay using DNA from peripheral white blood cells. Logistic regression was performed to calculate odds ratios (ORs), confidence limits (CL) and to control for possible confounders. The exon 3 polymorphism of the mEH gene was associated with a significantly decreased risk of lung cancer. The adjusted OR, calculated relative to subjects with the Tyr113/Tyr113 wild type, for the His113/His113 genotype was 0.38 (95% CL 0.20-0.75). An analysis according to histological subtypes revealed a statistically significant association for adenocarcinomas; the adjusted OR for the His113/His113 genotype was 0.40 (95% CL 0.17-0.94). In contrast, no relationship between the exon 4 polymorphism and lung cancer risk was found. The adjusted OR, calculated relative to the His139/His139 wild type, was for the Arg139/Arg139 genotype 1.83 (0.76-4.44). Our results support the hypothesis that genetically reduced mEH activity may be protective against lung cancer.

A cohort mortality and nested case-control study of French and Austrian talc workers.

OBJECTIVES: To study whether the mortality from non-malignant and malignant respiratory diseases of workers employed in French and Austrian talc mines and mills is related to their long term occupational exposure. METHODS: Two historical cohorts were set up comprising all male subjects who had been working continuously for at least 1 year in a series of talc producing companies in France and Austria. The French cohort consisted of those employed at a site in the French Pyrenees and working between 1 January 1945 and 31 December 1994. The Austrian cohort consisted of the workers employed between 1 January 1972 and 31 December 1995 in one of four industrial sites in the Austrian Alps. The mortality within the cohorts was compared with local death rates. Two nested case-control studies focusing on non-malignant and malignant respiratory diseases were set up to estimate possible dose-response relations with cumulative exposure to talc dust based on an industry specific job exposure matrix. RESULTS: Mortality from lung cancer was in small excess in both cohorts (France, standardised mortality ratio (SMR) 1.23, 21 cases observed, 95% confidence interval (95% CI) 0.76 to 1.89; Austria, SMR 1.06, seven observed, 95% CI 0.43 to 2.19). A non-significant excess mortality was found for all non-malignant respiratory diseases in the French cohort due to a significant excess for pneumoconiosis (SMR 5.56, three observed, 95% CI 1.12 to 16.2). The case-control study of non-malignant respiratory disease showed an increased mortality in the highest exposure groups (odds ratio (OR) 2.5 for a cumulative exposure > or = 800 y.mg/m(3)) with a significant trend (OR/100 y.mg/m(3) 1.08) with cumulative exposure to talc. On the contrary, no increasing trend could be found in the case-control study of lung cancer. This result must be interpreted considering the small cohort size. Adjustment on smoking and exposure to quartz did not influence these results to any extent. CONCLUSIONS: The mortality from non-malignant respiratory disease was found to be related to high cumulative exposure to talc dust. The small excess in lung cancer does not seem to be attributable to talc.

Cellular reaction on the anterior surface of 4 types of intraocular lenses.

PURPOSE: To assess the cellular reaction on the anterior surface of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Vienna, Austria. METHODS: One hundred eyes scheduled for cataract surgery were prospectively randomized into 4 groups of 25 eyes each using random number tables. Group 1 received a Hydroview IOL (Bausch & Lomb), Group 2 an AcrySof IOL (Alcon), Group 3 a MemoryLens IOL (ORC), and Group 4 a CeeOn 920 IOL (Pharmacia). Patients were examined 1, 3, 7, 30, 90, and 180 days postoperatively. Postoperative biomicroscopic examinations were done with a slitlamp, and a specular microscope was used to document the presence of cell deposits and identify areas with the highest density of cells. RESULTS: The local tissue response revealed 2 patterns: a nonspecific foreign-body reaction to the IOL (small round, fibroblast-like, epithelioid, and giant cells) and a lens epithelial cell (LEC) reaction. The highest incidence of LECs was in the Hydroview group, in which LECs were present on 81.8% of lenses 180 days postoperatively. During the first postoperative days, small round and fibroblast-like cells were found on all IOLs. From 7 days on, the incidence and density of these cells were less severe in the Hydroview and CeeOn 920 groups. After several weeks, epithelioid cells and foreign-body giant cells were seen on some IOLs. These cells appeared more often on AcrySof, MemoryLens, and CeeOn IOLs. CONCLUSION: This study found IOL-related differences in cellular reaction after cataract surgery. The incidence of a nonspecific foreign-body reaction to 4 IOLs is consistent with the results of previous studies. The incidence of LECs was highest in the Hydroview group and lowest in the AcrySof group. The CeeOn 920 group had the lowest incidence of all types of cells.

Influence of a beta-glucan-enriched bedtime snack on nocturnal blood glucose levels in diabetic children.

BACKGROUND: The high prevalence of low nocturnal blood glucose levels is a major problem in the treatment of children with diabetes. METHODS: The effect of a beta-glucan-enriched bedtime snack on nocturnal blood glucose levels was examined in comparison with an equicaloric conventional snack in 38 children with diabetes during a 12-night study period. RESULTS: A significant influence of the type of bedtime snack on the blood glucose course until 2 AM could be observed (P < 0.05). However, there was no difference in the prevalence of nocturnal hypoglycemic blood glucose levels, which was 27% at 2 AM. CONCLUSION: Silent nocturnal hypoglycemia is common in children with diabetes. The introduction of a fiber-enriched bedtime snack may flatten the blood glucose curve before midnight but cannot prevent low 2 AM blood glucose. Other therapeutic strategies that reduce the risk of asymptomatic and symptomatic nocturnal hypoglycemia would be beneficial to many children with diabetes.

High-altitude retinopathy and retinal vascular dysregulation.

PURPOSE: (a) To show that high-altitude retinopathy (HAR) is common at high altitudes even in well-acclimatised climbers and that it should not be regarded as part of the spectrum of benign mountain sickness but rather as a clinical sign with a separate aetiology. (b) To test the hypothesis that HAR could be interpreted as a clinical expression of 'ocular vascular dysregulation'. METHODS: Both eyes of the 8 mountaineers of the First Vienna Himalayan Expedition in May/June 1996 were examined 2 weeks before departure to and 2 weeks after descent from a high altitude. Retinal blood flow was measured in the right eyes of 7 climbers, using the Heidelberg Retina Flowmeter (HRF). RESULTS: Two of the 8 climbers had bilateral retinal haemorrhage after the expedition. In 5 climbers chronic hypoxic exposure caused an increase in retinal blood flow between +18% and +96%, and in 2 climbers a decrease in retinal blood flow between -21% and -31%. The 2 climbers (climbers 1 and 2) with bilateral retinal haemorrhage showed a significant increase in HRF parameters. CONCLUSIONS: HAR may be a clinical sign of mountaineers with a tendency towards ocular vascular dysregulation. The pronounced increase in all haemodynamic parameters in the 2 climbers with retinal haemorrhage combined with a dilated epipapillary network 2 weeks after the exposure reflects a retinal vessel configuration, as might be expected at high altitudes under acute hypoxic stress. An inadequate autoregulatory response of the retinal circulation under conditions of chronic hypoxia may play an important part in the pathogenesis of HAR.

Symptoms suggestive of atopic rhinitis in children aged 6-9 years and the indoor environment.

BACKGROUND: We aimed to investigate the influence of indoor factors on the prevalence of symptoms suggestive of atopic rhinitis in children aged 6-9 years in Upper Austria. METHODS: We analyzed the results from an extended ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire, answered by the parents, about indoor environment and symptoms strongly suggesting atopic rhinitis. This was defined as having reported a running, obstructed, or itchy nose apart from having a cold in the last year. The overall response rate was 93.4%. After excluding 6,016 children (17.1%) with changed indoor environment (due to allergies in the family), we analyzed the remaining subsample of 18,606 questionnaires. RESULTS: The following factors were associated with an increased risk: mother's smoking during pregnancy and/or during time of breast-feeding (OR 1.28; CI 1.07-1.52), synthetic bedding (OR 1.21; CI 1.09-1.36), dampness/mold at home (OR 1.51; CI 1.31-1.74), central heating with gas (OR 1.75; CI 1.06-2.87), and space heating (OR 1.66; CI 1.01-2.98). Cooking with wood (OR 0.62; CI 0.46-0.84) was negatively associated with symptoms. CONCLUSIONS: The indoor environment plays a role in the symptoms of atopic rhinitis in children. However, the population-attributable risks were not particularly high; they were between -2.7% and 9% for the various exposures considered in this study.

[Prevalence of smoking habits of Upper Austria students of the 7th and 8th grade and effect of smoking habits of family and peers]. / Prävalenz der Rauchgewohnheiten von oberösterreichischen Schülern der 7. und 8. Schulstufe und Einfluss der Rauchgewohnheiten von Familie und Peers.

The aim of the study was to explore the prevalence of different smoking habits in a population of Austrian pupils, 12 to 15 years old, and the relationship of familial and peer group smoking customs with these habits. In 1997 a population-based survey (International Study of Asthma and Allergies in Childhood, ISAAC) was conducted of all 7th and 8th grade school children of a district of Upper Austria. Information on the smoking habits of the adolescents, the family members, and of the peer as well as smoking habits of the teacher, gender, and age of the children was collected. The overall-prevalence of having ever smoked in this population is 57.8%. The percentage of eversmokers among the 12-year-olds is 50%. This amount increases to 63.8% among the 14- to 15-year-olds. The odds ratios for smoking daily is highest among those whose best friend smokes (OR: 70.63, CI: 9.19, 542.40). The risk of daily smoking increases also if the siblings of the juvenile (OR: 4.71, CI: 1.15, 19.35) or the mother (OR: 4.95, CI: 1.67, 14.70) smoke. If the father smokes the risk to smoke monthly is increased (OR: 2.09, CI: 1.28, 3.40). These results point to the fact that smoking prevention programes should take into account the influence of peers and family of the adolescents.

Longitudinal growth in HIV-negative boys with haemophilia.

UNLABELLED: It has been shown that HIV-positive haemophilic children develop growth retardation. As not only the HIV infection but also other disease-related factors might compromise growth in these children, growth data were analysed in a longitudinal cross-sectional manner in 84 HIV-negative haemophilic patients from two university clinics. A total of 2-24 height and weight measurements (median 6) were recorded in each patient resulting in 683 single values collected between 1977-1995. Height SDS of all haemophilic boys was -0.31 +/- 2.13 (mean +/- SD, NS versus 0) and body mass index SDS was 0.21 +/- 3.49 (mean SD, NS versus 0) at first measurement and remained unchanged throughout the observation period. Neither height nor body mass index differed with respect to the severity of haemophilia (mild/moderate/severe) or the study centre (Vienna/Prague). CONCLUSION: Growth in HIV-negative patients with haemophilia is not affected in spite of the immunological abnormalities attributed to the substitution therapy or the bleeding episodes in the joints with the potential effect on the growth plate.

Indoor factors and their association to respiratory symptoms suggestive of asthma in Austrian children aged 6-9 years.

The ISAAC (International Study of Asthma and Allergy in Childhood) was founded in 1990 in order to maximise the value of epidemiological research into asthma and allergic diseases, to describe the prevalence of asthma and allergic disease in children living in different locations, to make comparisons within and between countries, to provide a framework for further etiological research and to find prevention strategies. We analysed a sub-sample of a population-based study (1995 to 1997) in Upper Austria. The aim of our study was to investigate the influence of indoor risk factors on wheezing in children 6-9 years old. Our calculations were based on the results of a questionnaire answered by parents about their children's indoor environment at home. Smoking of the mother during pregnancy and/or during breastfeeding (OR 1.28; 95% CI 1.08-1.48), smoking of the mother at the present time (OR 1.25; 95% CI 1.12-1.41), a bird (OR 1.40; 95% CI 1.06-1.85) or rabbit (OR 1.37; 95% CI 1.03-1.82) as a domestic pet, synthetic bedding (OR 1.33; 95% CI 1.18-1.49) and dampness or mould at home (OR 1.43; 95% CI 1.24-1.65) are associated with a significantly increased risk of childhood wheezing in the last 12 months. Other variables such as "smoking of the father", "cooking with gas", "gas central heating" and other "pets" do not achieve statistical significance.

Personal light dosimetry in permanent night and day workers.

Light exposure was measured in six day and six night watches (working 12-hour shifts five days in a row) during 48 h on work days and 48 h on days off using a photocell with a sensitivity corresponding to photopic vision. The photocell was mounted on a frame of spectacles, thus measuring in viewing direction. Light exposure was low both in night and day watches; however, in night watches exposures were significantly lower: On work days, night watches spent a mean of 13 min above 1,500 lx, day watches 52 min; on days off, night watches spent 3 min above 1,500 lx but day watches 89 min. Unexpectedly, night watches had no higher exposure during days off. We suspect that this is due to a light avoidance tendency in permanent night workers. High negative correlations between the acrophases of subjective state (e.g., alertness and mood) and light exposure in night watches indicate that bright light would probably increase desynchronization between subjective state, sleep, and activity.

Enhanced mitotic activity induced by irradiation is abolished by PGI2 pretreatment.

It is well known that irradiation may induce pronounced vascular lesions. Experimental studies revealed that irradiation induces an increased mitotic activity. As PGI2 has been claimed to be an antilesional agent, we wondered whether a pretreatment with PGI2 might abolish some of the effects induced by irradiation. 2 Groups of 24 rabbits were studied. 8 Rabbits each were irradiated with either 5 or 10 Gy on an abdominal aortic segment; 8 animals were sham treated. In each of the 3 groups half of the animals (n = 4) received PGI2 and half the buffer vehicle only. It is demonstrated that PGI2 is able to depress the enhanced mitotic activity induced by irradiation. In comparison to the controls, vascular thromboxane formation is decreased, the temporary increase in PGI2-formation by the vessel wall is less pronounced, whereas the conversion of exogenous arachidonic acid is unchanged. It is hypothetized that stable PGI2-analogues given during irradiation may probably prevent at least in part radiation-induced vascular changes and finally radiation-induced vasculopathy; this claim has to be proven in human.

Additive benefit of PGI2 and PGE1 (via different mechanisms?) on inhibition of activation of human vascular smooth muscle cells?

It seems likely that the antiplatelet action of antiaggregatory prostaglandins (PGE1, PGI2) is not the pivotal mechanism of action involved in clinical improvement of peripheral vascular disease. Based upon earlier results that both of these agents may have a certain effect on proliferation of vascular smooth muscle cells, we approached that question of an "optimal therapeutic regimen" going one step further. Patients having to undergo amputation were given a randomized "last choice" therapy with either PGI2 (once or twice a day, 6 h, 5 ng/kg/min i.v.), PGE1 (once or twice a day, 1 ng/kg/min i.a.) or a combination of both with a 6 h interval in between for 5 consecutive days. The ones who underwent surgery had a pathomorphological examination of vascular segments removed during amputation. The counting of activated smooth muscle cells indicates a significant drop induced by both of the PG's alone. A second infusion a day with the same compound, however, did not induce a further decrease in the activation state. In contrast administering the complimentary PG caused a comparable, significant decrease (p less than 0.01) in activation of smooth muscle cells in the intima and the media as well. It thus seems, that different mechanisms may be involved inducing additive therapeutic benefit. PGI2 is hypothesised to act predominantly by blocking PDGF-release and interference with PDGF, whereas PGE1 may have a more direct vascular action. From these findings, as well as the beneficial clinical results to be reported elsewhere, a combined therapy by the infusion scheme used may be the optimal one for a PG-therapy at the moment, based upon platelet and smooth muscle cell action.

PGE1 reduces collagen and glycosaminoglycan synthesis in rabbit aorta.

In 18 male rabbits the influence of PGE1 on collagen and glycosaminoglycan synthesis assessed by means of the incorporation of radiolabelled precursors has been examined. It is demonstrated that PGE1 induces a 20-30% drop both in 14C-proline and 35S incorporation into the vessel wall. These findings are in line with earlier data on the inhibition of proliferation of smooth muscle cells and a decrease in mitotic activity. The results present one piece of evidence more that PGE1 is acting as an anti-atherosclerotic agent in vivo at the vascular level. This pathomechanism, as well as the fact that this vascular effect is achieved--in an animal experiment at least--via an intravenous PGE1-application, offers new basics for the treatment of atherosclerosis in man.

Stimulation of prostacyclin formation by the platelet-derived growth factor--an important pathomechanism for atherogenesis?

The capacity of vascular tissue in generating PGI2 has been accepted to be a key property in hemostatic balancing at a local level. Earlier it has been shown that PDGF is able to enhance SMC-proliferation. As this process is associated with c-AMP changes which again are influenced by PGI2, the question arose, whether PDGF itself exerts an effect on PGI2-synthesis. Using normal and atherosclerotic human arterial tissue, animal arteries and cultured cells with and without addition of various PDGF-concentrations this question was answered by means of bioassay and RIA-determination in a static and a pulsatile perfusion chamber system as well. In general, between 10 and 50 ng PDGF/ml, a significant increase either in PGI2-formation or 6-oxo-PGF1 alpha can be seen. A similar dose dependent stimulation of PGI2-synthesis can be monitored for vascular tissue and cultured cells as well. Static incubation and perfusion chamber experiments reveal comparable findings of PDGF stimulatory capacity on PGI2-formation. In contrast, no such effect can be seen using human umbilical artery. The half-life of PGI2-formation in the perfusion chamber model is comparable in presence and absence of PDGF as well. The stimulatory effect of PDGF on atherosclerotic vascular tissue is significantly less pronounced than onto normal one. Concluding from our findings we speculate that PGI2 prevents PDGF-release from platelets, thus decreasing smooth muscle cell proliferation and improving cellular lipid metabolism; an insufficient response of vascular tissue onto PDGF to generate PGI2 might be a key event in the pathogenesis of early atherosclerosis favouring a negative vicious cycle.

Platelet derived growth factor (PDGF) and prostaglandins (PGE1, PGI2) as modulators of the atherogenetic process.

It is concluded that the interaction between platelets, the PDGF- and PG-formation may be of key-importance in human atherosclerosis, not only by regulation of smooth muscle cell proliferation and extracellular matrix production but also in cellular lipid metabolism.