Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
  • A61B5/02007—Evaluating blood vessel condition, e.g. elasticity, compliance
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/02—Detecting, measuring or recording pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography or electroauscultation; Heart catheters for measuring blood pressure
  • A61B5/021—Measuring pressure in heart or blood vessels
  • A61B5/022—Measuring pressure in heart or blood vessels by applying pressure to close blood vessels, e.g. against the skin; Ophthalmodynamometers

Definitions

• This invention relates to method and apparatus for non-invasively monitoring blood pressure through use of a transducer array of individual pressure or force sensing elements, and to method and means for selecting the one pressure sensitive element which most closely tracks the true blood pressure waveform and gives the most accurate measure of blood pressure.
• a transducer which includes an array of pressure sensitive elements is positioned over a superficial artery, and a hold-down force is applied to the transducer so as to flatten the wall of the underlying artery without occluding the artery.
• the pressure sensitive elements in the array have at least one dimension smaller than the lumen of the underlying artery in which blood pressure is measured, and the transducer is positioned such that more than one of the individual pressure-sensitive elements is over at least a portion of the underlying artery.
• the output from one of the pressure sensitive elements is selected for monitoring blood pressure.
• the element that is subs antially centered over the artery has a signal output that provides an accurate measure of intraar terial blood pressure.
• the signal outputs generally do not provide as accurate a measure of in tr aart er ia 1 blood pressure as the output from the centered element.
• the offset upon which systolic and diastolic pressures depend, will not be measured accurately using transducer elements that are not centered over the artery.
• the pressure sensitive element having the maximum pulse amplitude output is selected, and in other arrangements the element having a local minimum of diastolic or systolic pressure which element is within substantially one artery diameter of the element which generates the waveform of maximum pulse amplitude is selected. The latter method is shown in the above-mentioned J.S. Eckerle patent No.
• Patent No. 4,269,193 The selection method disclosed in Patent No. 4,269,193 generally identifies the correct transducer element to be used.
• pressure readings provided by individual elements of a transducer array may not be perfectly accurate due to any number of factors. Even small errors in the pressure readings may result in the selection of an incorrect transducer element using the system disclosed in Patent No. 4,269,193, in which case the blood pressure measurements are inaccurate.
• An object of this invention is the provision of an improved tonometric type method and apparatus for non-invasively monitoring blood pressure with a high degree of accuracy.
• Another object of this invention is the provision of such a blood pressure measuring method and apparatus which includes the use of a transducer having an array of individual transducing arterial riders (pressure sensitive elements) and wherein means are provided for selecting the element which most closely reproduces the actual blood pressure waveform.
• the present invention includes an array of individual pressure sensitive elements, each of which elements have at least one dimension smaller than the lumen of the underlying artery in which blood pressure is measured.
• the elements are of sufficiently small size such that with the array positioned so as to extend across the artery a plurality of elements are located over the artery. Of course, the number of elements located over the artery will depend upon the artery diameter.
• artery diameter is related to the subject's sex, height, weight, age, arm and/or wrist dimension , or like anatomical or physiological attributes of the subject.
• the diameter of a child's artery generally is smaller than that of an adult, and arteries of females generally are smaller than those of males.
• outputs of all of the transducer elements are employed in locating the center of a search area which, ideally, is centrally located over the artery. Novel means, described below, are used to locate the center of a search area.
• transducer element to be used as the center of the search area outputs from a limited number of transducer elements are employed in selecting that element within the limited— num ber group which is to be used for obtaining blood pressure measurements.
• the number of transducer elements within the group of elements to be searched is dependent upon one or more anatomical or physiological attributes of the subject, such as mentioned above.
• the pressure sensitive element within the limited-number group that has a local minimum of at least one of diastolic and systolic pressures is selected as the element to use for monitoring blood pressure. Novel methods for locating the center of the search area include use of measurements of pulse amplitude.
• the difference between the systolic and diastolic pressure values is defined herein as the pulse amplitude of the blood pressure waveform.
• the graph of pulse amplitude versus transducer element includes two humps, or peaks, of substantially equal magnitude at the transducer elements which overlie the two edges of the artery.
• One novel method of this invention involves locating the transducer element that is midway between the two humps, which element then is taken as the center of the search area. A pair of local maxima may be found from the pulse amplitude values derived from outputs from the transducer elements of the array. Then, the transducer element centered between the elements with the local maxima is identified as the element at the center of the search area.
• Another novel means for locating the center of the search area includes fitting a polynomial of at least second order to the pulse amplitude values from the elements of the array.
• the element at which the pulse amplitude curve is maximum is selected as the element at the center of the search area.
• Further novel means for locating the center of the search area includes computing the center of gravity of the graph of pulse amplitude versus transducer element, with the element at the center of gravity being selected as the element at the center of the search area.
• Fig. 1 shows the external appearance of a blood pressure transducer case, typically positioned over an artery, for providing a continuous external measurement of arterial blood pressure
• Fig. 2 is a schematic diagram illustrating the force balance between the artery and the multiple transducer elements (arterial riders), with the artery wall properly depressed to give accurate blood pressure readings
• Fig. 3 is a combination simplified vertical sectional view taken through the transducer case of Fig. 1 and block diagram of a system which may be employed therewith in the practice of this invention
• Fig. 4 is a waveform of human blood pressure versus time of the type which may be obtained using the present invention for illustrating systolic and diastolic pressures and pulse amplitude of the blood pressure wave
• Figs. 5A and 5B together show a flow chart for use in explaining overall operation of this invention ;
• Fig. 6 shows plots of diastolic pressure and pulse amplitude versus transducer element obtained from a subject under ideal conditions
• Fig. 7 shows a pressure distribution which is similar to that of Fig. 6 from the same subject but under conditions that are not ideal;
• Fig. 8 is a flow chart showing details of the selection of the transducer element to be employed for monitoring blood pressure.
• Fig. 9 is a schematic diagram which is similar to that of Fig. 2 but showing only a transducer array and a large underlying artery such as the artery of an adult male.
• FIG. 1 A typical application of the transducer array for arterial tonometry is illustrated in Fig. 1 wherein the transducer housing, or case, 10 which may have the appearance of an ordinary wristwatch case, is held in place over the radial artery in a human wrist 12 by a band 14.
• a cord 16 extends from the transducer housing 10 through which electrical wiring for the transducer array within the housing, together with a small tube that connects the housing to an air pressure source, extend.
• the wiring 18 and tube 20 are shown in Fig. 3, but no in Fig. 1.
• FIG. 2 wherein a diagrammatic mechanical model is shown which is representative of factors to be considered in the physical system.
• the illustrated model is that shown in the above-mentioned J.S. Eckerle patent number 4,269,193 which was adapted from the G.L. Pressman and P.M. Newgard article entitled "A Transducer for the Continuous External Measurement of Arterial Blood Pressure".
• an array 22 of individual pressure sensitive elements or transducers 22-1 through 22-19 which constitute the arterial riders, is positioned so that one or more of the riders are entirely over an artery 24.
• the individual riders 22-1 through 22-19 are small relative to the diameter of the artery 24 thus assuring that a plurality of the riders overlie the artery.
• the skin surface 26 and artery underlying the transducer must be flattened by application of a hold- down pressure to the transducer.
• One rider overlying the center of the artery is identified as the "centered" rider, from which rider pressure readings for monitoring blood pressure are obtained.
• the present invention is directed to novel method and means for selecting the "centered" rider, and is described in detail hereinbelow.
• rider selecting means of this invention one of the riders, such as rider 22-10, may be selected as the "centered" rider, in which case the remainder of the riders, here riders 22-1 through 22-9 and 22-11 through 22-19 comprise "side plates" which serve to flatten the underlying skin and artery.
• a different transducer element may be positioned over the center of the artery and be selected as the "centered" rider.
• Superficial arteries such as the radial artery, are supported from below by bone which, in Fig. 2 is illustrated by ground symbol 28 under the artery.
• the wall of artery 24 behaves substantially like a membrane in that it transmits tension forces but not bending moments.
• the artery wall responds to the loading force of the transducer array, and during blood pressure measurements acts as if it is resting on the firm base 28.
• the effective stiffness of an artery wall is small and differs between subjects.
• This is illustrated schematically in Fig. 2 by showing the individual riders 22-1 through 22-19 backed by rider spring members 30-1 through 30-19, respectively, a rigid spring backing plate 32, . and hold-down force generator 36 between the backing plate 32 and the mounting strap system 38.
• hold-down force generator 36 comprising (in the present example) a pneumatic loading system, is included to keep constant the force applied by the mounting strap system 38 to riders 22-1 through 22-19.
• hold-down force generator 36 comprising (in the present example) a pneumatic loading system
• k force per unit of deflection
• Suitable pneumatic loading systems are shown and described in the above- referenced U.S. Patent numbers 3,219,035 and 4,269,193, and the Pressman and Newgard IEEE article.
• transducer array 22 The actual physical structure of a practical transducer of a type which may be employed for transducer array 22 in the present system is shown in the above-mentioned J.S. Eckerle patent No. 4,269,193.
• a transducer array is shown in which the individual transducers (riders) are formed in a thin monocrystalline silicon substrate which is made using integrated circuit fabrication techniques.
• Fig. 3 to which reference now is made, a simplified showing of transducer 22 is shown comprising a chip 40 which includes an array of individual transducers, not shown. Electrical conductors 42 connect the individual transducers to the wiring 18 for connection thereof to a multiplexer 43. As seen in Fig.
• case 10 comprises a generally cylindrical, hollow, container having rigid back and side walls 44 and 46, respectively.
• the silicon transducer chip 40 is mounted within the face 48 of the case (designated as the front or operative face) in a cylindrical cup-like transducer housing 50.
• the operative face 48 includes the silicon transducer chip 40 along with its included individual transducers and arterial riders.
• Chip 40 may be affixed to a conventional ceramic dual in— line package that is plugged into an associated dual in-line socket, neither of which are shown in the drawings.
• a silicone rubber filler 52 is provided inside the housing 50 and around the dual in-line package and socket to provide a good seal, prevent electrical leakage between the transducer circuits and housing 50, and provide a flat surface to press against the subject.
• the front face 48 of the transducer includes the lower faces of housing 50 and filler 52.
• the transducer housing 50 is fixed to the . inside of the transducer case 10 by means of a cup-like silicone rubber bladder 54 which is sealed around the lower outside lip of the cup-shaped transducer housing 50, extends upwardly inside the outer wall of the transducer case 10, and is sealed to a ring 56, which in turn is fixed and sealed to the inside back of the transducer case 10.
• a chamber is formed inside the bladder which is connected to . an air pressure source 58 through ube 20.
• a pressure controller 58A may be included in the pressure source. Since the flexible bladder 54 is sealed both to the transducer housing 50 and the inside of the transducer case 10, air under pressure from source 58 pneumatically loads the operative face 48.
• the hold-down force Fi exerted by the transducer array against the skin of the subject is adjustable by control of the air pressure.
• the hold-down force Fi is generated by hold-down force generator 36.
• electrical signals related to pressure sensed by the individual transducers 22-1 through 22-19 of transducer 22 are supplied as inputs to an analog multiplexer 43. From the multiplexer, the signals are digitized by an a na lo g- to -d i it al (A-D) converter 60, and the digitized signals are supplied to a digital computer 62 having memory 62A and a clock 62B.
• Other information such as the subject's name, sex, weight, height, age, arm and wrist dimensions, and the like, are supplied to the computer through a keyboard 64. As described hereinbelow, this information is used to make an estimate of the diameter of the artery of the subject, which then is used to establish the range of transducer elements that will be employed in selecting the "centered" rider after the center of the search region has been established.
• Output from the computer is supplied to data display and recorder means 66 which may include a recorder, cathode ray tube monitor, a solid state display, or the like. If desired, at least a portion of the visual display may be included in transducer case 10. Obviously, the computer output may be supplied to a printer, an audible alarm, or the like, as desired. Also, an output from the computer is supplied over line 68 to the pressure controller for control of the transducer hold-down pressure.
• Fig. 4 the signal waveform of the output from one of the pressure sensitive elements 22-1 through 22-19 which overlies artery 24 is shown. Other elements of the transducer array which overlie the artery will have waveforms of similar shape.
• the waveform is representative of the blood pressure within the underlying artery.
• Systolic, diastolic and pulse amplitude pressures are indicated on the waveform, wherein pulse amplitude is the difference between the systolic and diastolic pressures for a given heartbeat.
• FIG. 5A and 5B together show a flow chart of an algorithm for general, overall, operation of the blood ressure monitoring system.
• Some of the operations indicated therein are under control of computer 62 responsive to programming instructions contained in memory unit 62A.
• Obviously, several program steps may be involved in the actual implementation of the indicated operations. Since the programming of such steps is well within the skill of the average programmer, a complete program listing is not required and is not included herein.
• Preparation for monitoring is begun at START step 100 at which time system power is turned on or a reset operation is performed, by means not shown, and counters, registers, timers, and the like in computer 62 are initialized.
• a nominal hold-down pressure (H-D.P.) is applied wherein air under pressure from source 58 is supplied to the transducer.
• H-D.P. a hold-down pressure of say 120 mmHg may be supplied to the transducer, which pressure serves to extend the bladder 54 whereby operative face 48 extends outwardly a short distance from the bottom of the case
• the transducer is attached to the subject at step
• step 106 is entered at which point systolic and diastolic pressures are determined from the outputs of each transducer element, and pulse amplitude values are determined by subtraction of the diastolic pressure values from the systolic pressure values.
• Step 110 then is entered wherein the transducer element to be used in monitoring blood pressure is selected.
• step 110 may require repositioning of the transducer for properly locating it relative to the underlying artery.
• the hold-down pressure to use to obtain accurate blood pressure measurements is computed at step 116.
• Algorithms which may be used in computing the correct hold-down pressure are disclosed in the above— mentioned patent application serial number 927,843, filed November 6, 1986.
• a correct hold-down pressure for accurate blood-pressure monitoring is computed at step 116, following which, at step 118, the computed hold-down pressure is set by control of pressure controller 58A by the computer 62.
• the system With the transducer properly positioned on the subject and the correct hold-down pressure supplied thereto, the system is in condition for obtaining accurate blood pressure readings.
• an indication that the system is operative is provided, as by display of the words "Readings Valid".
• other displays such as a green indicator light, may be employed for indicating the operating state of the system.
• systolic and diastolic pressure values together with pulse amplitude values are readily determined in step 122.
• pulse rate is readily calculated by determining the time between successive diastolic or systolic pressures.
• values calculated and determined in step 122 are displayed and/or recorded along vith the actual waveform. Obviously, the values which are calculated and displayed depend upon the use to be made of the blood pressure monitor, a display of all of the values not being required in many instances. For example, the blood pressure waveform could be recorded without calculation and display of any of the values identified in step 122.
• step 126 is entered wherein the system waits for the next heartbeat cycle. Diastolic or systolic pressure points may be used to identify reference points in the heartbeat cycles. Decision step 128 then is entered at which time a timer in computer 62 is tested to determine whether or not it has reached a predetermined time "M", where M is a time period of, say, 30 minutes.
• step 130 If the elapsed time exceeds the predetermined time period, M, wherein the decision is affirmative, the timer is reset at step 130, hold-down pressure is reduced to a pro imately 120 mmHg at step 131, and step 116 is reentered for r e c om p u t a t i o n of the correct hold-down pressure and resetting thereof, if required. Periodic checking and resetting of hold- down pressure helps to assure continued accuracy of the blood pressure readings.
• step 132 is entered for selection of the transducer element to. be used for monitoring, which step is substantially the same as step 108 described above.
• step 108 ("centered") transducer element determined in step 108 (or the previous execution of step 132) is compared to that determined in step 132. If there is no change in selected transducer elements, step 120 is reentered indicating that the readings are valid. However, if there has been a change in the selected transducer element, such that decision step 134 is affirmative, then a warning is issued at step 138 indicating to the subject or operator that movement of the transducer relative to the artery has taken place. If desired, the transducer then may be repositioned and the process restarted.
• step 120 is reentered fo-r continuation of the monitoring process, but now using the output from the newly selected "centered" transducer element.
• Fig. 6 wherein a typical pressure distribution is shown which may be obtained from outputs of transducer elements 22-1 through 22-19 of transducer array 22 placed over superficial artery 24.
• Fig. 6 both the distribution of diastolic pressures and the distribution of pulse a'mplit udes are shown.
• the systolic pressure distribution is very similar to the distribution of diastolic pressures, being displaced vertically by about 40 mmHg.
• diastolic and pulse amplitude distributions are shown and described.
• a similar statement can be made concerning systolic pressures.
• the center of the underlying artery is nearest to transducer element number 10.
• a local minimum of diastolic pressure is produced at transducer element 22-10 (element 10 in Fig. 6). It will be seen then that the system shown in U.S. Patent 4,269,193 will correctly identify and select the transducer element located nearest the center of the underlying artery when extremely accurate pressure distributions are provided by the tonometer transducer .
• step 110 selection of the transducer element for monitoring (step 110) takes place with the transducer attached to the subject (step 106) and with a nominal hold-down pressure of, say, 120 mmHg supplied to the transducer. It here will be noted that during blood pressure monitoring a much larger hold- down pressure generally is employed, often in the range of 150-220 mmHg, as determined in step 116.
• step 150 the center of the search region is located using pulse amplitude data from all of the transducer elements of the array.
• methods for locating the center of the search area include, 1) a "center of gravity” method, 2) a “two-humps” method, 3) a “curve fit” method, and, 4) a combination of methods 1) - 3).
• center of Gravity Method With the center of gravity method of finding the center of the search region, the center of gravity of the pulse amplitude values for all of the transducer elements in the array is determined, and the transducer element at the center of gravity is selected for the center of*the search area. Computation of the center of gravity is a well-known procedure which is readily implemented by computer 62.
• n 1 where n is a variable representing the transducer element number (it is assumed here that the elements are equally- spaced), N is the total number of elements in the tonometer transducer, and A n is the pulse amplitude measured by the n ⁇ transducer element.
• Fig. 7 data the computed value of ring is 9.94. This value may be "rounded — off" to the nearest integer, 10, indicating that transducer element 10 is the element at the center of the search area. 3.
• the two-hump method involves searching the distribution of pulse amplitude values for the maximum, then identifying the second largest local maximum.
• local maxima of pulse amplitude often are located over the edges of the underlying artery.
• the transducer element midway between the two largest local maxima then is taken as the center of the search area. If an even number of transducer elements are included between elements having the two local maxima, then the point midway between the two will be halfway between two adjacent elements. Either of the adjacent elements may be selected as the element at the center of the search area. In Fig. 7, it can see by inspection that there are two local maxima in the pulse amplitude distribution at elements 7 and 12.
• element 9 or 10 may be selected as the element at the center of the search area.
• element 9 or 10 may be selected as the element at the center of the search area.
• the two-hump method is not operable.
• the two-humps when the two-humps are present, they generally identify the two edges of the artery, and the method works well for identifying the center of the search area. This method of identifying the transducer element midway between two largest local maxima of the pulse amplitude distribution is readily implemented using computer 62.
• the curve fit method of locating the center of the search area includes fitting a polynomial of at least second order to the full set of pulse amplitude versus transducer element number values.
• a preferred method fits a second-order polynomial to the pulse amplitude data, but third and higher-order polynomials might be used without departing from the teachings of the invention.
• the dashed line labelled "polynomial" in Fig. 7 shows approximately the curve that would be produced from a second-order polynomial fit to the pulse amplitude data.
• the point on the graph of the polynomial at which the pulse amplitude is maximum is taken as the center of the search area.
• a second-order polynomial fitted to the measured pulse amplitude pressure values may be written as follows:
• a combination of the above- described methods may be employed in locating the center of the search region.
• the double-hump method first may be employed, and if the pulse amplitude distribution includes a pair of local maxima, then the element midway therebetween may be employed. If the distribution does not include a pair of local maxima that are comparably large (e.g. the second maximum is greater than some substantial fraction, say 70%, of the first) then one or more of the other methods may be used . Alternatively, two or more of the methods may be employed, and results thereof compared. If the same transducer element is identified using the different methods, then that element is selected as the center of the search region. If adjacent elements are identified, then one of them may be selected, and if the elements are widely spaced, then none would be selected and the process would be repeated on the next heartbeat and/or an error or warning message would be issued by the computer 62.
• decision step 152 is then entered to determine whether or not the element selected for the center of the. ⁇ earch area is sufficiently near the center of the transducer array. If it is not, the transducer is repositioned on the subject at step 154, and step 108 is reentered. The process is repeated until the transducer is properly located on the subject.
• the location of the element selected for the center of the search area in the array is displayed. If desired, the exact transducer element 22-1 through 22-19 selected at step 150 may be displayed at step 152. Alternatively, a linear array of, say, three lights may be provided wherein energization of the center light indicates that a centrally located transducer element was selected at step 150. Illumination of either of the end lights would indicate that movement of the transducer to the right or left is required for proper positioning of the transducer array relative to the underlying artery.
• step 152 Determining Size, or Extent, of Search Region
• This step involves both knowledge of the dimensions of the pressure sensitive elements of the transducer, and knowledge of the diameter of the subject's artery. Knowledge of the diameter of the subject's artery need not be directly known. Instead, the size of the artery may be estimated from other factors such as the subject's age, sex, height, weight, arm or wrist dimension, or the like, physical, anatomical or physiological information. As noted above, these known factors are entered into computer 62, as through use of keyboard 64.
• the artery diameter of a male adult generally is larger than that of a female adult which, in turn, is generally larger than that of a young child.
• An artery diameter on the order of 1.5 mm, 1.1 mm and 0.7 mm for an adult male, an adult female, and a young child, respectively, may be typical in some population groups for a given underlying artery.
• Weight, height and wrist or arm diameter also provide indications of artery diameter.
• the transducer array 22 is shown overlying an artery 24A which is of a male adult, which artery is of subs antially larger diameter than artery 24 shown in Fig. 2.
• the Fig. 2 artery may be that of a child of approximately 12 and, based upon that information, might be assumed to be on the order of 0.7 mm diameter.
• the larger diameter male adult artery shown in Fig.9 may be estimated to have a diameter of 1.5 mm.
• the region to be searched includes the center element located at step 150 and 7, 5 and 3 elements on either side thereof for the adult male, adult female and young child, respectively.
• transducer elements need not be located in a single straight line, but may be located at staggered positions along parallel lines, for example, to provide for a close "effective" ce nt er -t o-cent er spacing of elements across the artery.
• step 158 Selecting Element within Search Region For Monitoring After the center of the search region is established (steps 150 and 152; item B, above) and the extent of the search region is determined (step 156; item C, above) the transducer element to be used for monitoring blood pressure is selected at step 158. At this step, only those elements that are within the search region are examined in the selection of the element to be used for monitoring.
• the pressure sensitive element within the selected region that generates the signal having a local minimum of. at least one of the systolic and diastolic pressures is selected for monitoring.
• transducer element 10 is identified as the center element using the center of gravity and curve fitting methods (methods B2 and B4, above) and either element 9 or 10 is selected using the two-hump method (method B3, above) depending upon the round-off rule employed.
• the element within one artery radius of the element identified as the center element (either element 9 or element 10) having a local minimum of diastolic pressure is element 10.
• Element 10 is, in fact, the element centered over the underlying artery.
• both systolic and diastolic pressures may be checked, in which case the same element normally is identified. This element then is selected for use in measuring blood pressure. However, if different elements are identified, then the process of locating the element to be used may be repeated on subsequent heartbeats until a single element is identified. Alternatively, a warning or error message may be generated by computer 62 when the systolic and diastolic local minima do not occur at the same element.
• analog or digital circuit means, or a combination thereof may be employed for processing the blood pressure waveforms instead of the illustrated digital computer. It is intended that the above and other such changes and modifications shall fall within the spirit and scope of the invention defined in the appended claims .

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• 1987
  • 1987-01-27 US US07/007,038 patent/US4802488A/en not_active Expired - Lifetime
  • 1987-12-09 DE DE19873790884 patent/DE3790884T1/de not_active Withdrawn
  • 1987-12-09 EP EP88900515A patent/EP0299992B1/en not_active Expired - Lifetime
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• 1988
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