A new method of post-dialysis blood urea sampling: the `stop dialysate flow' method

Colin C. Geddes, Jamie Traynor, David Walbaum, Jonathan G. Fox and Robert A. Mactier

Renal Unit, Stobhill Hospital, Balornock Road, Glasgow, Scotland, UK

Correspondence and offprint requests to: Dr R. Mactier, Renal Unit, Stobhill Hospital, Balornock Road, Glasgow G21 3UW, Scotland, UK.



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
Background. A standardized practical method of post-dialysis blood sampling is required to improve the precision of using urea kinetics in the evaluation of haemodialysis dose and to permit comparative audit. The methods recommended in the Renal Association and Dialysis Outcomes Quality Initiative (DOQI) guidelines reduce the blood pump speed to a low rate at the end of haemodialysis before blood sampling after 10 and 15 s respectively. However, these `low flow' methods compensate only partially for cardiopulmonary recirculation and may be impractical in routine practice because they involve sequential steps and require accurate timing of sampling. Therefore we have evaluated an alternative method of stopping only the dialysate flow at the end of the haemodialysis session before performing post-dialysis blood sampling.

Methods. The study was performed in three phases. Serial measurements of blood urea were obtained from arterial and venous samples taken at times 0, 30, 60, 120, 180, 240, 300 and 360 s after stopping dialysate flow and leaving the extracorporeal blood flow rate unchanged at the end of the haemodialysis session in 10 patients. A peripheral venous sample was also taken from the contralateral arm at 0 s to reflect body water urea concentration at the end of dialysis without the effect of access recirculation and with a minimal effect of cardiopulmonary recirculation. The same haemodialysis prescription was repeated in the same 10 patients using the Renal Association method to permit comparison between the two methods. The practical use of the `stop dialysate flow' method was then evaluated in 117 regular haemodialysis patients undergoing routine monthly assessment of dialysis adequacy and compared with sampling immediately post-dialysis.

Results. Within 4 min of stopping the dialysate flow there was no difference between the blood urea concentrations of arterial and venous samples, indicating cessation of diffusion across the dialysis membrane. Also the blood urea concentrations in all of the arterial and venous samples between 4 and 6 min were constant and were equivalent to the blood urea concentration of the peripheral venous sample taken at 0 s. These data suggest that post-dialysis blood sampling may be performed 5 min after stopping dialysate flow at the end of the haemodialysis session. In contrast, the blood urea concentration in the post-dialysis samples obtained using the Renal Association method were lower than the contralateral arm blood urea concentration taken at 0 s (0.31±0.42; P<0.05) and consequently the percentage URR was higher (1.35±1.84%). In 117 patients the post-dialysis blood urea sample 5 min after stopping dialysate flow averaged 5.49±2.11 mmol/1 compared with 5.07±2.05 mmol/l immediately after the end of the haemodialysis session (P<0.0001). This was equivalent to a reduction in URR from 71.7±8.3% with sampling immediately post-dialysis to 69.1±9.3% with the `stop dialysate flow' method.

Conclusions. This study shows that there is a window period between 4 and 6 min after stopping dialysate flow at the end of the haemodialysis session when the blood urea concentration in a sample taken from any part of the extracorporeal circuit remains constantly within the co-efficient of variation of laboratory measurement, and is equivalent to a peripheral venous sample taken immediately at the end of the dialysis session. A `stop dialysate flow' method with blood sampling after 5 min offers several advantages over `slow flow' methods, since it allows for cardiopulmonary as well as access recirculation, does not require precise timing of blood sampling, and is simple to perform in a busy renal unit. For these reasons the `stop dialysate flow' method may be used for routine monitoring of the adequacy of delivered haemodialysis and for comparative audit among haemodialysis centres.

Keywords: adequacy; haemodialysis; post-dialysis sampling; renal failure



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
The survival of patients on chronic haemodialysis is directly related to fractional urea clearance [1,2]. For this reason, measurements of urea removal are used to monitor the adequacy of haemodialysis and to compare the quality of haemodialysis delivery among dialysis centres [3]. There are several methods of measuring urea removal in haemodialysis and the current recommended methods are measurement of Kt/V by formal urea kinetic modelling, calculation of an estimated single pool Kt/V, or calculation of the urea reduction ratio (URR) [4,5]. All of these methods require the measurement of the urea concentration of pre- and post-dialysis blood samples to calculate urea clearance. The timing of blood sampling for estimation of post-dialysis urea concentration is critical since there may be significant overestimation of urea removal if the method of post-dialysis blood sampling does not allow for post-dialysis urea rebound. The dilutional effects of access recirculation and (in subjects dialysing through arteriovenous fistulae) cardiopulmonary recirculation cease within 2 min of stopping haemodialysis and account for 69% of total post-dialysis urea rebound [68]. A delay in post-dialysis blood sampling for at least 30 min is needed to allow for tissue rebound due to intercompartmental urea dysequilibrium at the end of haemodialysis but this approach is impractical in routine clinical practice. There is currently no `gold standard' for post-dialysis blood sampling for calculation of urea removal; however, a standardized method that corrects for the major part of urea rebound occurring within the first 2 min of stopping haemodialysis should be available for the routine assessment of dialysis dose and for comparative audit.

The Renal Association (UK) and the National Kidney Foundation (USA) Dialysis Outcomes Quality Initiative (DOQI) guidelines currently recommend `slow flow methods' of post-dialysis blood sampling because they negate the effects of access recirculation, but they compensate only partially for cardiopulmonary recirculation [4,5]. The `slow flow method' of the Renal Association guidelines involves four steps that require accurate timing, and sampling is performed during the period of most rapid urea rebound [4,9]:

Similarly the `slow flow' method recommended in the DOQI guidelines is also a four-step procedure [5]:

The workgroup of the National Kidney Foundation DOQI guidelines acknowledged that in busy haemodialysis units `the rigor needed to execute the "slow flow" method cannot always be provided by the dialysis technicians' [5]. A survey in early 1998 of the 11 adult haemodialysis units in Scotland found that none of the units employed a `slow flow method' of taking the post-dialysis blood sample to calculate urea clearance (personal communication, S. Green, Scottish Haemodialysis Nurses Core Group). Ten units employed immediate post-dialysis sampling from the arterial line. This method therefore underestimates the post-dialysis blood urea concentration and overestimates urea removal because of access and cardiopulmonary recirculation The other haemodialysis centre performed post-dialysis sampling after the blood in the extracorporeal circuit had been re-infused (`re-infusion method'). This method is also imprecise because the time taken to re-infuse blood is variable and because of dilution with infused saline. A recent survey of North American dialysis facilities revealed that there were at least 20 post-dialysis sampling methods in use, and that up to 41.6% of the centres surveyed were using a method of post-dialysis blood sampling that did not allow for the effects of access and cardiopulmonary recirculation and were therefore overestimating urea removal by dialysis [10]. A recent report from the Dialysis Outcomes and Practice Patterns Study (DOPPS) has shown that units that obtained the post-dialysis sample more than 3 min after the end of haemodialysis had a 7% lower estimated Kt/V than patients with blood sampling between 30 and 60 s post-dialysis, and introducing a -0.1 Kt/V correction in all patients with post-dialysis sampling before 3 min increased the proportion of the patients receiving a Kt/V below 1.2 from 26% to 36% [11]. These observations emphasize both the importance of timing and the need for standardization of the method of post-dialysis sampling.

This study describes a new method of post-dialysis blood sampling after stopping the dialysate flow at the end of the dialysis session for 5 min instead of reducing extracorporeal blood flow to a low rate for 10 or 15 s [4,5]. By leaving the extracorporeal blood flow rate unchanged the `stop dialysate flow' method should avoid the risk of clotting in the extracorporeal circuit, which may occur if more prolonged low blood flow rates were recommended with a `slow flow method' to allow fully for the effects of both access and cardiopulmonary recirculation. After dialysis ceased after stopping the dialysate flow at the end of the haemodialysis session it was predicted from previous studies that access recirculation would stop after 30 s, cardiopulmonary circulation would cease after 2 min, and a `window period' may exist over the next few minutes when the effect of rebound of urea from tissues would be minimal [8,12] This hypothesis was confirmed. This `stop dialysate flow' method was compared to the Renal Association `slow flow method' [4] and was also then compared with immediate post-dialysis sampling, which was the method in current use in most Scottish haemodialysis units.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
The study was conducted in three phases

(i) Evaluation of the `stop dialysate flow' method
The blood urea concentration in the arterial and venous ports was analysed serially for several minutes after stopping dialysate flow to identify if there was a `window period' when the blood urea concentration in the extracorporeal circuit may represent the post-dialysis urea concentration without the effects of access or cardiopulmonary recirculation [12]. Ten subjects on haemodialysis for end-stage renal failure who had been clinically well over the preceding month and had functioning arteriovenous fistulae (usual mean blood flow >300 ml/min) were invited to participate and gave written informed consent. The demographics and haemodialysis prescriptions of the subjects are summarized in Table 1Go. Pre-dialysis blood was aspirated (Ureapre) from the arterial limb of the arteriovenous fistula before the introduction of heparin or saline and at the end of the prescribed dialysis session dialysate flow was switched off (time 0). Ultrafiltration was also stopped. The blood pump remained at the usual prescribed flow rate. Blood was sampled from both the arterial port (before the dialyser) and venous port (after the dialyser) at time 0, 30, 60, 120, 180, 240, 300 and 360 s. Blood was sampled from the contralateral arm at time 0 (contralateral t0) to obtain a representative sample of body water urea concentration immediately at the end of haemodialysis without the effect of access recirculation and with a minimal effect of cardiopulmonary recirculation. Three investigators conducted the serial blood sampling to ensure exact timing. Urea concentration in the arterial port samples (A0, A30, A60, A120, A180, A240, A300, A360) was compared with urea concentration in the contralateral t0 sample to identify a `window period' when access and cardiopulmonary recirculation had ceased, tissue rebound was minimal, and the blood urea concentration was relatively constant. Urea concentrations in the samples from this time period were compared with A0. Urea concentrations in samples from the venous port (V0, V30, V60, V120, V180, V240, V300, V360) were compared with the corresponding arterial samples to identify when equilibration with the dialysate remaining in the dialyser occurred.


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Table 1. Summary of the demographic and haemodialysis prescriptions of the 10 subjects studied
 
Results were expressed as mean±standard deviation (SD). Statistical comparison was by paired t-test.

(ii) Comparison of `stop dialysate flow' and `slow flow' methods
Post-dialysis blood was sampled using the `slow flow' method described by the Renal Association [4] in the same 10 subjects on a separate dialysis session and a contralateral time 0 sample was again taken to represent the post-dialysis blood urea concentration immediately at the end of haemodialysis without the influence of access recirculation and with a minimal effect of cardiopulmonary recirculation. The differences between post-dialysis blood circuit urea : contralateral t0 urea were determined and compared for the `slow flow' and `stop dialysate flow' methods. The urea clearance was compared for these two methods by deriving URR and Kt/V using the following formulae:

where Ureapost is post-dialysis blood urea concentration and Ureapre is the pre-dialysis blood urea concentration [1,3];

where Ln is the natural logarithm, R is the post-dialysis blood urea/pre-dialysis blood urea, t is the dialysis session length in hours, UF is the ultrafiltration volume in litres, and W is the post-dialysis weight in kilograms [13].

(iii) Comparison of the `stop dialysate flow' method with immediate post-dialysis sampling
The `stop dialysate flow' method was compared with immediate post-dialysis sampling in the same dialysis session in all 117 patients on hospital haemodialysis in Stobhill Hospital. All of the blood samples were taken by nursing staff to assess if the method was applicable for routine use. The blood urea concentration using the `stop dialysate flow' method was compared with the blood urea concentration in the arterial limb of the arteriovenous fistula at time 0. The urea clearance was compared for these two methods by calculating URR (see formula above).

All results were expressed as mean±SD. Statistical comparison was by paired t-test of means. For comparison between the `stop dialysate flow' and `slow flow' methods, the results were expressed as the difference from the values of the contralateral t0 sample obtained at the end of the same dialysis session.

Measurement of blood urea concentration
Blood urea concentrations were measured by the kinetic urease method (Sigma Chemical Co. Ltd) on an Olympus discrete analyser (Au 5200). For each dialysis session, all samples were analysed in the same batch. The coefficient of variation of urea concentrations in the range of urea concentrations under evaluation was 0.8% for all samples batch tested from an individual dialysis and 2% for samples from different dialysis sessions.

Ethical approval was obtained from the local research and ethics committee.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
Identification of a `window period' using the `stop dialysate flow' method
Post-dialysis blood urea concentrations in serial samples from the arterial port after switching off dialysate flow at the end of the prescribed dialysis session in the 10 subjects are shown in Table 2Go. The mean blood urea concentration in A0 is significantly lower than A240, A300, and A360 (5.18±2.41 vs 5.75±2.42, P=0.01; 5.84±2.43, P=0.004; 5.85±2.47, P=0.003 respectively). There was no significant difference between the mean urea concentration in A240, A300, and A360. The mean blood urea concentrations in serial samples from the arterial and venous ports after stopping dialysate flow at the end of haemodialysis are shown in Figure 1Go. There was no difference between urea concentration in A240, A300, A360 and V240, V300, V360 respectively, indicating that by 4–6 min the dialysate remaining in the dialyser after stopping dialysate flow had equilibrated with blood urea.


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Table 2. Evaluation of stop dialysate flow method
 


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Fig. 1. Mean arterial and venous blood urea concentrations after stopping dialysate flow expressed as a fraction of blood urea concentration of contralateral arm at time zero versus time (n=10).

 
Figure 1Go shows the urea concentration in serial samples from the arterial and venous ports expressed as a fraction of the contralateral time 0 urea. The urea concentrations in A240, A300, and A360 were the same as in contralateral time 0 (5.85±2.54, P=0.58, P=0.95, P=1.00 respectively). Mean blood urea concentrations and URR of the contralateral arm time 0 urea are compared with post-dialysis sampling at sequential times after stopping dialysate flow in Table 2Go. These results indicate that the blood urea concentrations and hence the URR derived from A240, A300, and A360 are equivalent to the contralateral arm time 0 blood urea concentration and URR.

On the basis of these data, 300 s (5 min) after switching off dialysate flow was selected as the appropriate time to sample blood from the extracorporeal circuit for the `stop dialysate flow' method.

Comparison of `stop dialysate flow' and `slow flow' methods
The pre- and post-dialysis blood urea concentrations using both the `stop dialysate flow' method with blood sampling after 5 min and the Renal Association `slow flow' method with the same haemodialysis prescriptions in the same 10 patients are compared in Table 3Go. The mean post-dialysis urea concentrations were similar to the contralateral arm time 0 urea in the `stop dialysate flow' method but significantly lower than the contralateral arm time 0 urea concentration in the `slow flow' method (6.29±2.80 and 5.98±2.66, P=0.043). Consequently the derived URR with the `slow flow' method was significantly higher than the URR calculated from the contralateral arm time 0 urea concentration (72±7 and 70±7%, P=0.045). Differences in blood urea concentrations and URR between the contralateral arm time 0 and the `stop dialysate flow' and `slow flow' blood sampling methods are summarized in Table 4Go. Post-dialysis blood urea concentrations and URR in samples between 240 and 360 s after stopping dialysate flow and the contralateral arm time 0 were equivalent, but were significantly different from results of sampling using the `slow flow' method or immediately after the end of haemodialysis (P<0.05).


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Table 3. Comparison of pre- and post-dialysis blood urea concentrations by the `stop dialysate flow' and `slow flow' methods on two separate dialysis sessions in the same 10 subjects. Ureapre=pre-dialysis urea; ureapost=post-dialysis urea; contralateral time0=contralateral arm venous sample taken immediately at the end of haemodialysis session
 

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Table 4. Comparison of urea kinetics using `stop dialysate flow' and Renal Association `slow flow' methods
 
Comparison of `stop dialysate flow' method with blood sampling immediately post-dialysis
The post-dialysis blood urea measured using a sample taken immediately at the end of the dialysis session was significantly lower than the post-dialysis urea measured by the `stop dialysate flow' method at the end of the same dialysis session in 117 hospital haemodialysis subjects who were having routine monthly urea clearance measurements (5.07±2.05 mmol/l vs 5.49±2.11 mmol/l, P<0.0001). The corresponding URR, calculated using immediate post-dialysis sampling, was significantly higher than the URR calculated using the `stop dialysate flow' method. (72±8 vs 69±9%, P<0.0001). Cumulative URR data using `stop dialysate flow' and no slow flow methods are compared in Figure 2Go. The cumulative URR data in the haemodialysis population was shifted significantly to the left using the `stop dialysate flow' method instead of immediate post-dialysis blood sampling and converted six patients (5% of the patients studied) with an URR above 65% to below the current minimum standard of the Renal Association [4]. In a subset of 23 patients using double-lumen central venous catheters (six temporary and 17 permanent catheters) for haemodialysis blood samples were taken from the venous as well as the arterial lumen after stopping the dialysate flow for 5 min. The mean blood urea concentrations in the arterial and venous samples were similar (5.99±2.9 and 5.91±2.84 mmol/l respectively, P=0.45) indicating that blood sampling with the `stop dialysate flow' method can be obtained from any part of the extracorporeal circuit.



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Fig. 2. Cumulative URR using `no slow flow' method (0 s) and `stop dialysate flow' method (5 mins).

 


   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
These data show that the `stop dialysate flow' method is a useful and valid new method for post-dialysis blood urea sampling for monitoring of haemodialysis adequacy. Blood sampling from any part of the extracorporeal circuit 5 min after stopping the dialysate flow at the end of the haemodialysis session was shown to be equivalent to blood sampling from the contralateral arm immediately after the haemodialysis session was completed (Table 2Go). This `stop dialysate flow' method therefore compensates for the initial urea rebound, which occurs during the first 2 min after stopping haemodialysis due to access and cardiopulmonary recirculation. This study shows that for the first 4 min after stopping the dialysate flow at the end of a haemodialysis session dialysis still takes place into the dialysate within the dialyser as the urea concentration in blood leaving the dialyser is initially lower than blood entering the dialyser (Figure 1Go). However, this small amount of dialysis occurring into a stagnant pool of dialysate within the dialyser will have no significant influence on haemodialysis adequacy. The range and frequency of use of different dialysers and the duration and efficiency of haemodialysis were similar in the three study phases and are representative of current haemodialysis prescribing practice. Between 4 and 6 min after stopping dialysate flow the urea concentration from the arterial port remains relatively constant and there is also no difference between the urea concentrations in samples from the venous and arterial ports, indicating equilibration with the dialysate remaining in the dialyser (Figure 1Go). There is also no difference between the dialysis circuit blood urea between 4 and 6 min after stopping dialysate flow and the contralateral arm venous sample at time 0 (contralateral t0) confirming that access and cardiopulmonary recirculation are no longer lowering the dialysis circuit blood urea concentration (Figure 1Go). Although blood urea concentrations remained relatively constant between 4 and 6 min it may be anticipated that the blood urea concentration would rise slowly over the next 30 min due to tissue rebound, although this was not assessed in the present study [8,12].

It is not possible to compare the `stop dialysate flow' and `slow flow' methods in the same haemodialysis session for technical reasons. The two methods were compared in the same subjects on different haemodialysis sessions in the same month by using the blood urea concentration in a contralateral arm venous sample at time 0 post-dialysis as a reference. This showed that the blood urea concentration post-dialysis is slightly lower when measured using the `slow flow' method (Table 3Go). This is expected, as the `slow flow' method does not negate the effect of cardiopulmonary recirculation, which is important since Schneditz et al. showed that failing to take cardiopulmonary recirculation into account results in a 6–14% overestimation of urea removal [14]. Obtaining a blood sample without waiting for access and cardiopulmonary recirculation to cease was shown in the present study to significantly underestimate systemic urea concentration by approximately 10% (Table 2Go) and therefore overestimate urea removal when compared to the `stop dialysate flow' method (Table 4Go).

A contralateral arm venous sample immediately after the haemodialysis session was used in this study to estimate body water urea concentration at the end of dialysis and permit comparisons between the `stop dialysate flow', `slow flow', and no slow flow methods of post-dialysis sampling. Some authors have raised doubts regarding the validity of using samples from the contralateral arm as an index of post-dialysis body water urea concentration [15]. Depner et al. have shown that blood urea concentrations in samples from the contralateral arm during and after high-efficiency haemodialysis were higher than the blood urea concentration in the arterial port after the fistula had been occluded between the arterial and venous needles for 1 min to limit the effect of access recirculation [15]. This finding was attributed to haemodialysis-induced compartment dysequilibrium in the relatively poorly perfused contralateral arm [15] but is at least partly due to the differential effects of cardiopulmonary recirculation in the arteriovenous and contralateral arms [14]. Thus contralateral arm venous sampling at the end of haemodialysis is an acceptable reference method of obtaining a representative post-dialysis blood sample for urea kinetics but it is not practical for routine use.

There are several technical advantages with the `stop dialysate flow' method described in this study over the `slow flow' method. The `stop dialysate flow' method negates the effect of cardiopulmonary as well as access recirculation whereas recommended `slow flow' methods [4,5,16] only allow partially for cardiopulmonary recirculation. A `slow flow' method would need to delay blood sampling for at least 2 min to obviate the effects of both access and cardiopulmonary recirculation [17], which would confer an increased risk of thrombosis in the extracorporeal circuit when perfused at a low flow rate, especially since many renal units discontinue heparin for the last 30 min of haemodialysis. The `stop dialysate flow' method requires only one step by the dialysis technician or nurse before taking the blood sample (i.e. stopping the dialysate flow at time 0). The Renal Association `slow flow' method [4] requires three steps before blood sampling (i.e. stopping ultrafiltration and clamping the arterial tubing exactly 10 s after slowing blood flow to 50–100 ml/min). Other recommended `slow flow' methods [5,16] also involve multiple steps requiring accurate timing of blood sampling during the early post-dialysis period of most rapid urea rebound, which is likely to decrease the precision of urea measurement. The timing of sampling with the `stop dialysate flow' method is not as critical as with a `slow flow' method, since the variability in blood urea concentrations at 4, 5, or 6 min after stopping dialysate flow is small and is within the reported co-efficient of variation of urea measurements. The sample can be taken from the arterial or venous port with the `stop dialysate flow' method, whereas it is critical that the correct tubing is clamped and sampled when using the `slow flow' method. The most likely technical error with the `stop dialysate flow' method is forgetting to switch off the dialysate flow. If this is recognized during the procedure, then the dialysate flow can be switched off and the sample can be taken 5 min later. Errors using the `slow flow' method cannot be corrected once they have occurred.



   Conclusion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 
A standardized, practical method of post-dialysis blood sampling which reliably measures the true post-dialysis urea concentration would improve prescription of adequate haemodialysis therapy and allow meaningful comparisons between haemodialysis centres. The `stop dialysate flow' method with blood sampling after 5 min offers several advantages over `slow flow' methods since it:

For these reasons the `stop dialysate flow' method of post-dialysis blood sampling may be used for the routine monitoring of adequacy of delivered haemodialysis and for comparative audit in haemodialysis units.



   Acknowledgments
 
This study was presented in part at the meeting of the Scottish Renal Association in Dumfries, November 1998.



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Conclusion
 References
 

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  15. Depner TA, Rizwan S, Cheer AY, Wagner JM, Eder LTI. High venous urea concentrations in the opposite arm. A consequence of haemodialysis-induced compartment disequilibrium. ASAIO Trans 1991; 7: 141–143
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Received for publication: 22. 3.99
Accepted in revised form: 4.11.99