GB2031148A - Control substances for monitoring haemogasanalysis - Google Patents
Control substances for monitoring haemogasanalysis Download PDFInfo
- Publication number
- GB2031148A GB2031148A GB7932497A GB7932497A GB2031148A GB 2031148 A GB2031148 A GB 2031148A GB 7932497 A GB7932497 A GB 7932497A GB 7932497 A GB7932497 A GB 7932497A GB 2031148 A GB2031148 A GB 2031148A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/15—Reference solutions for assays of biological material containing dyes to mimic optical absorption of, e.g. hemoglobin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/70—Blood gas control solutios containing dissolved oxygen, bicarbonate and the like
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
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- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
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- Food Science & Technology (AREA)
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- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A liquid haemogasanalysis control substance for use in the quality control of haemogasanalysis contains a phosphate-based buffer solution and is gas balanced at three different levels of pH, partial pressure of carbon dioxide and partial pressure of oxygen corresponding to the normal, acid and alkaline ranges of the blood being monitored. The substance basically comprises water, a phosphate, sodium chloride, sodium bicarbonate, a bactericide and a predetermined mixture of carbon dioxide, oxygen and nitrogen. The substance may also include glycerol and it may be coloured. Preferably the control substance is filled into ampoules at the required levels of pH and partial gas pressures under controlled, sterile conditions.
Description
SPECIFICATION
Control substances for monitoring haemogasanalysis
Haemogasanalysers are instruments that allow the measurement of pH, partial carbon dioxide pressure and partial oxygen pressure in the blood by means of electrodes. The use of such instruments has expanded greatly in recent years and consequently the number of haemogasanalyses has increased proportionally. Like other chemical analyses, the gas-analysis of blood requires very accurate results in order to have an equally accurate and precise diagnosis, since even small variations in the measured values can be significant. Furthermore it is important to remember that pH, partial carbon dioxide pressure (Pco2) and partial oxygen pressure (Po2) are often parameters that are necessary to determine the therapeutic treatment of acutely ill patients, as for instance those undergoing intensive care or therapy.
Therefore, the desirability of being able to carry out a quality control in haemogasanalysis will be evident.
A more valid means to balance a liquid with a gas is known as a Tonometer and as reference material the whole blood is drawn, if possible, from the same sample to be analysed. An aliquot sample of whole blood is balanced with a gaseous mixture with known values of Pco2 and Po2.
The introduction of the standard sample of blood, so obtained, into the haemogasanalyser allows an exact control of the values of Pco2 and Po2 in the equipment.
The advantages of this method are essentially due to the possibility of carrying out the control with whole blood, thus eliminating eventual differences arising from the liquid composition.
Nevertheless, inconveniences such as the time which is required to carry out the operation, the care with which it must be conducted, the need of having corefully analysed gas mixtures, the cost of the needed instrumentation, and the manual nature of the operation tend to restrict the more general use of this method. Moreover, even if the Tonometered whole blood allows the control of the Pco2 and Po2 parameters, it cannot be used for the pH value control. This measurement is usually carried out with phosphate-based buffer solutions, prepared according to the specifications of the U.S.A. National Bureau of Standards (NBS).
Therefore, there is a need to be able to provide a system for the quality control of haemogasanalysis that is fast, simple and adequate without the need to resort to special procedures or equipments.
The use of gas balanced buffer solutions in ampoules has already been recognised as the most convenient and practical for the customary or "routine" control of haemogasanalysers. The use of ampoules is very simple; each ampoule is agitated for about ten seconds, then opened and its liquid content is aspired by the haemogasanalyser.
A composition contained in an ampoule has been described in U.S. Patent 4,001,142 and it contains a buffer solution based on triethanolamine. However, the ionic force obtained with this buffer is not close enough to that of whole blood and, moreover such buffer involves a different situation from that obtained with the phosphate-buffer used in the pH calibration.
The present invention is concerned with the preparation of a phosphate-formulated, gasbalanced buffer solution with known values for pH Pco2 and Po2 contained in an ampoule that shows an excellent stability at temperatures of 4"C, 25"C and 37"C; the invention also concerns a method of manufacturing the solution that allows an excellent reproducibility within each batch and between batches, i.e, with very close values in the same batch preparation lot and from one batch to another. The control solution is packaged in three kinds of ampoule which reproduce different clinical levels of acid-base equilibrium; that is normal, acid and alkaline.
The selected buffer solution comprises dibasic sodium or potassium phosphate and monobasic sodium or potassium phosphate in equimolar concentration, with the addition of sodium bicarbonate and sodium chloride. The total concentration of phosphates is preferably of 50 mmol/l. The choice of the phosphate buffer, in accordance with the present invention meets the following requirements: the phosphate buffer can be recommended for the pH standardisation in haemogasanalysers; it enables quality control to be performed using a buffer of the same type as the one used for calibrating the instruments Furthermore, this buffer emphasises better than other known buffers any incorrect response by the pH-electrode.
Another positive aspect of this buffer is that of having, in the ampoule, a product stability of more than two years between 4"C-37"C. This result was not previously obtainable with other types of buffers such as TRIS (hydroxymethylamino-methane and triethanolamine).
The molar concentration of the bicarbonate added to the phosphate buffer is different for the three kinds of ampoule and an equilibrium is created between bicarbonate concentration and dissolved CO2. Taking advantage of this equilibrium and selectively changing the bicarbonate concentration and the percentage of CO2 of the gas mixture of tonometry, combinations of pH and Pco2, corresponding to the three desired levels, can be obtained.
To achieve this aim it was necessary to study thoroughly the pH curves as a function of the bicarboate concentration for given levels of Pco2, also taking into account the equilibrium variation due to the difference between the tonometry temperature of the buffer solution (25"C), and that of the instrument reading (37"C). As a result of these studies it was possible to fix, for each of the three levels, the optimal ratios between NaHCO2 concentration and CO2 (percent) of the gas mixture to obtain the desired pH, and Pco2 combination.
Also, to obtain the Po2 values corresponding to the three levels, it was necessary to study the Po2 curves as a function of the oxygen percent in the tonometry gaseous mixture, taking into account that the solution is tonometered at 25"C, whereas the instrument reading takes place at 37"C.
The sodium chloride was added to the phosphate buffer so that the sum of bicarbonate and sodium chloride concentration would be constant and preferably equal, for the three levels, at 60 mmol/l; working in this manner, the molarity of the final solution is constant in all types of ampoules and as a consequence, preferably equal at 110 mmol/l, which corresponds to an ionic force of about 0, 16, very close to that of whole blood. This final concentration was not only selected for the similarity with whole blood but also because, according to our experiments, 0, 1 6 is the optimal ionic force in which the haemogasanalysers work on the pH line.
The buffer solvent can be deionized water or deionized water plus about 30% of glycerol. The presence of 30% glycerol involves a viscosity and a potential diffusion like that of whole blood and the same oxygen tension. For this reason the addition of glycerol supplies a product very similar to whole blood as regards the "Blood gas Factor" i.e. the electrode response difference between a gas mixture and a liquid balanced with the same mixture.
An antibacterial substance can be added to the buffer solution to prevent contaminations during the processing. The sodium trichlorophenate showed itself to be a good bactericide.
Other tested bactericides, as the quaternary ammonium salts, presented difficulties concerning pH and Po2.
The possibility of colouring the solution in order to observe the flow of the liquid into the instrument and eventually differentiate the three types of ampoules was also investigated. The selected dyes were Red E 1 23 (FISC Red No. 2) and Red E 1 24 (Food Red No. 7), and Yellow
E 102 (FISC Yellow No. 5) The use of mixtures of dyes E 102 + El 24 and E102 + E 123 in definitive ratios such as to give an orange colour of the desired intensity was also studied. The selection was made on the ground of both the solubility and light stability of the dye, and as well as its compatability with the buffer solution and the instrument.
In United States Patent 4,001,142 referred to above a production process, which provided that the buffer solution equilibrium be obtained directly in ampoules is disclosed. The production process to which the present invention is directed provides instead, that the buffer solution is balanced with a gas mixture formed by oxygen, carbon dioxide and nitrogen in a Tonometer, and then subsequently filled into the ampoules.
The Tonometer used for the method of this invention consists of a container which is, for example, of cylindrical form that can have different dimensions according to the required capacity. On the inside of the Tonometer can be inserted a mixer so as to assure a complete homogeneity in the liquid-gas system, a device for the inlet and the diffusion of gases as minute bubbles into the solution in order to carry out the tonometry and devices for the control of temperature, pH, Pco2, and Po2; moreover a system which allows the transfer of the tonometered liquid to the ampoule filling machine.
Inside the Tonometer the temperature is kept at a usually constant 25"C by a jacket system through which a cooling liquid circulates. The temperatures of 25"C was selected after many tests at different temperatures and on the basis of precise considerations. First of all it is the closest to room temperature so that the difficulty in avoiding changes in temperature in the tonometered solution when this is transferred to the filling machine, is greatly reduced.
Furthermore, the temperature of 25"C allows the use of an ampoule for the control of the instrument without preincubation at 25"C if the product is kept between 20 and 30"C so obtaining results that are practically identical to those obtained after the preincubation at 25"C.
This helps to increase the practicality of the product obtained in accordance with the invention.
The internal pressure of the Tonometer is kept constant and similar to the external temperature.
The gas mixture (O2-CO2-N2) used for the tonometry is fed by gas cylinders with a capacity of 40 litres and a maximum pressure of 1 50 atm.
At the outlet the gas undergoes a reduction to the desired pressure, then it passes through a flow-meter to determine the required flow rate and then it is sent to a humidifier kept at 25"C, and from there the gas is passed to the Tonometer. The tonometry time for five litres of buffer solution is about four hours, with a gas mixture flow rate of 0,5 1 /min.
The tonometered solution is placed in the ampoules by an automatic filling machine, in connection with which studies were made of devices that allow a previous flushing of the ampoule with the same gas mixture as that for the tonometry, the filling of the ampoules in the same gas atmosphere and maintaining the ampoule under the same gas atmosphere as for the tonometry from the moment of filling to the moment of sealing.
The study and the setting up of these devices were of major importance to eliminate the possibility of air contamination of the tonometered liquid, thus contributing to the production of a product characterised by an exceptional reproducibility in each batch and between batches, also at industrial production level.
Ampoules not containing glycerol can be sterilised in an autoclave at 120"C for one hour.
Some non-limiting examples are referred to as preferred formulations to produce the three liquid controls of this invention.
Example No. i-Normal Level
Preparation of a solution for the quality control in the haemogasanalysis having mean values of pH 7,35, Pco2 45 mmHg, and Po2: 90 mmHg.
Deionized water quant. suff. to 1000 ml
Glycerol 300 ml
Sodium and potassium phosphates 50 mmol/l
Sodium bicarbonate 36 mmol/l
Sodium chloride 24 mmol/l
Sodium trichlorophenate 0,1 g/l
Gas mixture: 5,000% CO2, 12,3% 02, Balance N2
Water is mixed with glycerol. In this, phosphates, bicarbonate, sodium chloride and trichlorophenate are dissolved. The solution is filtered through millipores of 0,22 jum, then it is transferred to the Tonometer and balances at 25"C with the gas mixture. The tonometered solution is then placed in ampoules of 1 ml that are subsequently sealed. The ampoules are then analysed in the hemogasanalyser and the values of pH, Pco2 and Po2 at 37"C are fixed.
Example No. 2:-alkaline level
Preparation of a solution for the quality control in haemogasanalysis having mean values of pH 7,55, Pco2 20 mmHg, Po2: 145 mmHg.
Deionized water: quant. suff. to 1000 ml
Glycerol 300 ml
Sodium and potassium phosphates 50 mmol/l
Sodium bicarbonate 28 mmol/l
Sodium chloride 32 mmol/l
Sodium trichlorophenate 0,1 g/l
Gas mixture: 2.27% CO2, 21,15% 02, Balance N2.
The preparation is the same as in Example 1.
Example No. 3: acid level
Preparation of a solution for the quality control in the haemogasanalysis having mean values of pH 7,20, Pco2: 70 mmHg, Po2: 60 mmHg.
Deionized water quant. suff. to 1000 ml
Glycerol 300 ml
Sodium and potassium phosphates 50 mmol/l
Sodium bicarbonate 34 mmol/l
Sodium chloride 26 mmol/l
Sodium trichlorophenate 0,1 g/l
Gas mixture: 7,8% CO2, 6,8% 02, Balance N2.
The preparation is the same as in Example No. 1.
Claims (23)
1. A liquid control substance in three ranges corresponding to normal, acid and alkaline ranges for use in the quality control of haemogasanalysers, which comprises water, a phosphate, sodium bicarbonate, a sodium chloride buffer, a bactericide agent, and dissolved quantities of carbon dioxide, oxygen and nitrogen.
2. A liquid control substance according to claim 1 wherein the substance includes glycerol.
3. A liquid control substance according to claim 2, wherein the glycerol concentration is 30%.
4. A liquid control substance according to any one of claims 1 to 3, wherein the bactericide agent is sodium trichlorophenate or another phenol derivative.
5. A liquid control substance according to any one of claims 1 to 4, wherein the phosphate buffer comprises 25 mmol/l of dibasic potassium or sodium phosphate and 25 mmol/l of monobasic potassium or sodium phosphate.
6. A liquid control substance according to any one of the preceding claims, wherein the proportions of sodium bicarbonate and sodium chloride are such that the sum of their concentrations is always equal to 60 mmol/l.
7. A liquid control substance according to any one of the preceding claims wherein the substance includes a dye.
8. A liquid control substance according to claim 7, wherein the substance is coloured with a dye selected from the groups of the Reds E 1 23 (FISC Red. No. 2) and E 1 24 (Food Red No.
7) and from the group of Yellows E 102 (FISC No. 5), each of them being used at the concentration of 60 mg/l, or with a mixture of two dyes prepared with Red E 1 23 or E 1 24 (20 mg/l) and Yellow E 102 (40 mg/l) in order to obtain an orange colour.
9. A liquid control to be used as a quality control in a haemogasanalyser and corresponding to the normal level comprising water, 30% glycerol, a phosphate buffer 50 mmol/l, sodium bicarbonate 36 mmol/l, sodium chloride 24 mmol/l, sodium trichlorophenate or the like, balanced with a gas mixture having the composition 5,0% CO2, 12,3% O2 and the balance nitrogen and having a pH value between 7,35 and 7,40.
1 0. A liquid control substance to be used as a quality control for a hamogasanalyser corresponding to the acid level comprising water, 30% glycerol, phosphate buffer 50 mmol/l, sodium bicarbonate 34 mmol/l, sodium chloride 26 mmol/l, sodium trichlorophenate or the like balanced with a gas mixture having the composition 7,8% CO2, 6,8% 02 and the balances nitrogen and having a pH value between 7,12 and 7,22.
11. A liquid control substance to be used as a quality control for a haemogasanalyser corresponding to the alkaline level comprising water, 30% glycerol, phosphate buffer 50 mmol/l, sodium bicarbonate 28 mmol/l, sodium chloride 32 mmol/l, sodium trichlorophenate or the like, balanced with a gas mixture having the composition 2,27% CO2, 21, 15% 02, the balance nitrogen and having a pH value between 7,50 and 7,65.
1 2. A liquid control substance according to any of Claims 9 to 11 wherein the substance includes a dye.
1 3. A liquid control substance according to Claim 12, wherein the dye comprises Red E 123 or E 124 or Yellow E 102 or a mixture of Red and Yellow dye.
14. A liquid control substance corresponding to the normal level to be used for quality control in a haemogasanalyser including water, phosphate buffer 50 mmol/l, sodium bicarbonate 41 mmol/l, sodium chloride 19 mmol/l, sodium trichlorophenate or the like balance with a gas mixture having the composition 5,07% CO2, 11, 79% O2 the balance nitrogen and having a pH value between 7,34 and 7,41.
1 5. A liquid material corresponding to the acid level to be used as quality control in a haemogasanalyser including water, phosphate buffer 50 mmol/l, sodium bicarbonate 37 mmol/l, sodium chloride 23 mmol/l, sodium trichlorophenate or the like, balanced with a gas mixture having the composition 7,89% CO2, 6,17% 02, the balance nitrogen and having a pH value between 7,15 and 7,25.
1 6. A liquid material corresponding to the alkaline level to be used as quality control in a haemogasanalyser including water, phosphate buffer 50 mmol/l sodium bicarbonate 39 mmol/l sodium chloride 21 mmol/l, sodium trichlorophenate or the like, balanced with a gas mixture having the composition 2,25% CO2, 19,4% 02, the balance nitrogen and having a pH value betwen 7,55 and 7,65.
1 7. A liquid control substance according to any one of Claims 14 to 1 6 wherein the substance includes a dye.
1 8. A liquid control substance according to Claim 17, wherein the substance is coloured with Red E 1 23 or Yellow E102 or with a mixture of red and yellow dye.
1 9. A process for the preparation of a liquid control substance, in ampoules at three levels, corresponding to the normal, acid, and alkaline ranges respectively for the quality control of haemogasanalysers, said process including the preparation of a phosphate buffer in water or a mixture of water and glycerol with a composition according to any one of the preceding claims, the filtration of the buffer solution through a 0,22 micron filter, the balancing of the solution with a gas mixture of carbon dioxide, oxygen and nitrogen carried out at controlled temperature with the aid of an electrode system which allows the control of the tonometric process through the temperature, the pH value, the partial carbon dioxide pressure and the partial oxygen pressure, transferring the tonometered solution to an ampoule-filling machine and the filling of the ampoules with the tonometered solution by means of a filling machine equipped with means to prevent the contamination of the tonometered solution by air and the eventual sterilisation in an autoclave of the sealed ampoules.
20. A process according to Claim 1 9 wherein the controlled temperature of the tonometric apparatus is fixed at 25"C.
21. An ampoule containing a liquid haemogasonalysis control substance substantially as hereinbefore described.
22. A liquid haemogasanalysis control substance substantially as herein before described with reference to the examples.
23. A process for the preparation of a liquid haemogasanalysis control substance substantially as hereinbefore described.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT27885/78A IT1098867B (en) | 1978-09-20 | 1978-09-20 | SOLUTIONS PREPARED WITH PHOSPHATE BUFFER AND BALANCED WITH GAS, PACKAGED IN VIALS WITH THREE DIFFERENT LEVELS OF PH, PC02, AND P02, INTENDED FOR THE QUALITY CONTROL OF THE BLOOD-GAS TANKS; FORMULATION OF SUCH SOLUTIONS AND PROCESS FOR THEIR INDUSTRIAL PREPARATION |
Publications (1)
Publication Number | Publication Date |
---|---|
GB2031148A true GB2031148A (en) | 1980-04-16 |
Family
ID=11222535
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB7932497A Withdrawn GB2031148A (en) | 1978-09-20 | 1979-09-19 | Control substances for monitoring haemogasanalysis |
Country Status (9)
Country | Link |
---|---|
BE (1) | BE878877A (en) |
DE (1) | DE2938142A1 (en) |
DK (1) | DK390779A (en) |
ES (1) | ES484244A1 (en) |
FR (1) | FR2436991A1 (en) |
GB (1) | GB2031148A (en) |
IT (1) | IT1098867B (en) |
NL (1) | NL7906967A (en) |
SE (1) | SE7907526L (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4469792A (en) * | 1980-12-31 | 1984-09-04 | Allied Corporation | Blood gas calibration and control fluid utilizing stroma-free hemoglobin |
EP0181033A1 (en) * | 1984-11-05 | 1986-05-14 | Akzo N.V. | Control for blood gas analyzers and hemoglobin analysis |
US6599746B1 (en) * | 1998-06-04 | 2003-07-29 | Walter Gumbrecht | Calibration fluid for calibrating a sensor for measuring a blood value and methods for producing and using the fluid |
US7175759B2 (en) * | 2001-12-12 | 2007-02-13 | Linde Aktiengesellschaft | Apparatus and a method for controlling the alkalinity and pH of an industrial process |
CN113974578A (en) * | 2021-10-27 | 2022-01-28 | 川北医学院 | Device for estimating physiological heart measurement according to qi and blood analysis |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4250051A (en) * | 1978-12-26 | 1981-02-10 | Coulter Electronics, Inc. | Preservative for use in calibrator compositions for blood analysis |
JPH0287055A (en) * | 1988-09-24 | 1990-03-27 | Terumo Corp | Calibrating solution of sensor and calibrating method therefor |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4001142A (en) * | 1975-07-25 | 1977-01-04 | Warner-Lambert Company | Blood gas control |
GB1555626A (en) * | 1977-02-28 | 1979-11-14 | Radiometer As | Package containing a reference liquid for blood gas equipment |
-
1978
- 1978-09-20 IT IT27885/78A patent/IT1098867B/en active
-
1979
- 1979-09-11 SE SE7907526A patent/SE7907526L/en unknown
- 1979-09-18 ES ES484244A patent/ES484244A1/en not_active Expired
- 1979-09-19 NL NL7906967A patent/NL7906967A/en not_active Application Discontinuation
- 1979-09-19 BE BE0/197219A patent/BE878877A/en unknown
- 1979-09-19 GB GB7932497A patent/GB2031148A/en not_active Withdrawn
- 1979-09-19 DK DK390779A patent/DK390779A/en unknown
- 1979-09-19 FR FR7923346A patent/FR2436991A1/en not_active Withdrawn
- 1979-09-20 DE DE19792938142 patent/DE2938142A1/en not_active Withdrawn
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4469792A (en) * | 1980-12-31 | 1984-09-04 | Allied Corporation | Blood gas calibration and control fluid utilizing stroma-free hemoglobin |
EP0181033A1 (en) * | 1984-11-05 | 1986-05-14 | Akzo N.V. | Control for blood gas analyzers and hemoglobin analysis |
US6599746B1 (en) * | 1998-06-04 | 2003-07-29 | Walter Gumbrecht | Calibration fluid for calibrating a sensor for measuring a blood value and methods for producing and using the fluid |
US7175759B2 (en) * | 2001-12-12 | 2007-02-13 | Linde Aktiengesellschaft | Apparatus and a method for controlling the alkalinity and pH of an industrial process |
CN113974578A (en) * | 2021-10-27 | 2022-01-28 | 川北医学院 | Device for estimating physiological heart measurement according to qi and blood analysis |
Also Published As
Publication number | Publication date |
---|---|
BE878877A (en) | 1980-01-16 |
SE7907526L (en) | 1980-03-21 |
IT7827885A0 (en) | 1978-09-20 |
ES484244A1 (en) | 1980-05-16 |
DE2938142A1 (en) | 1980-04-03 |
IT1098867B (en) | 1985-09-18 |
NL7906967A (en) | 1980-03-24 |
FR2436991A1 (en) | 1980-04-18 |
DK390779A (en) | 1980-03-21 |
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WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |