While this method retains all the advantages highlighted in the aforesaid PCT/GB92/01041 document, it has the added advantage which allows for all measurements from a subject to be calibrated to give results which are equal to those expected from a common method employed in clinical practice. Also, this improvement provides an apparatus which will measure quantities in blood biochemistry, haematology, and blood gas, to further reduce costs in management, reduce trauma and discomfort to the patient. To make all the measurements required in critical care for an example, the apparatus requires the following;- a) monitoring the blood pressure; the pulse rate; and the oxygen saturation of blood; b) measurement of the subject's body surface area ; the plasma total proteins concentration; and the blood haemoglobin concentration.

It is an object of this improvement to the aforementioned PCT/GB92/01041 document to provide an apparatus which is calibrated for clinical use, which measures non invasively the blood related internal parameters of blood organs and quantities in blood biochemistry, haematology, and the blood gas of a subject.

According to one aspect of this improvement to the aforementioned PCT/GB92/01041 document, there is provided a calibrated non invasive method for evaluating blood related internal parameters of blood organs of a subject and making measurements of quantities in blood biochemistry, haematology and blood gas, the method comprising:- a) measuring a quantity T, the plasma total proteins concentration of a subject to evaluate the primary key factor range of an uncalibrated measurement, to place the measurement into a school; b) utilising a value CLa of an uncalibrated measurement to evaluate the class index and place the measurement into a class; wherein for an example the value CLa for the central venous pressure is represented by the equation:- CLa = (M (SA/1.8) S2)/ (P. K (S-D))-C c) utilising a quantity KC to evaluate the ratio in the result CFSM from a measurement made by a common method in clinical practice, and, the result CFs from the corressponding measurement evaluated using the uncalibrated equation for the measurement by this improved non invasive method; wherein the value Kc is represented by the equation:- KC = CFSM/CF5 d) utilising a quantity DX to evaluate the value of the quantity KC for an uncalibrated measurement; wherein the value of DX is represented by the equation:- i) DXH = KCH- (((HCLa-XCLa) (KcH-KCL))/ (HCLa-LCLa)) ii) DXL = KCL + (((XCLa-LCLa) (KcH-KCL))/ (HCLa-LCLa)) e) utilising a quantity Kps the unit change of the value of the quantity Kc relative to the unit change in the value of the range for a class from a school of each of the parameters in the equation required to evaluate the quantity CFs; wherein the value Kps is represented by the equation:- Kps = (KCH-KCL)/ (QuH-QuL) utilising a quantity DXL the net change of the DX value relative to the net change in the value of the quantity Kps for an uncalibrated measuremnt when the value of the quantity QuL is greater than the value of the quantity QuLx from the uncalibrated measurement for a class from a school; wherein the value DXL is representd by the equation:- DXL = DX- ( (QuL-QuLx) Kps) g) utilising a quantity DXH the net change of the DX value relative to the net change in the value of the quantity Kps for an uncalibrated measuremnt when the value of the quantity QuH is lower than the value of the quantity QuHx from the uncalibrated measurement for a class from a school; wherein the value DXH is representd by the equation:- DXH = DX + ( (QuHx-QuH) Kps) h) utilising the value of the quantity kn wherein kn is the result of having progressed in tandem where applicable in the DXL and DXH mode which are collectively used to adjust the value of the quantity DX and, otherwise, kn is equal to DX. i) measuring a quantity Hgb, the haemoglobin concentration of the blood of a subject; j) measuring a quantity U, the oxygen saturation of the blood of a subject; k) measuring a quantity SA, the body surface area of a subject; 1) monitoring the rate of beating P of the heart of the subject; m) monitoring the systolic blood pressure S of the subject; n) monitoring the changes (S-D) in the pressure of the subject's blood during beating of the heart; o) monitoring the body temperature of the subject; p) utilising a value R in the process of calibration of measurements of the said internal parameters; wherin the value R is represented by the equation:- R= (S-D) q) utilising a value Pp in the process of calibration of measurements of the said internal parameters; wherin the value Pp is represented by the equation:- Pp=P(S-D) According to another aspect of this improvement to the aforementioned PCT/GB92/01041 document, there is provided a calibrated non invasive apparatus for evaluating blood related internal parameters of blood organs of a subject and making measurements of quantities in blood biochemistry, haematology and blood gas, the method comprising:- a) means for obtaining measurements corressponding to a quantity T, the plasma total proteins concentration of a subject to evaluate the primary key factor range of an uncalibrated measurement, to place the measurement into a school; b) evaluating means utilising a value CLa of an uncalibrated measurement to evaluate the class index, to place the measurement into a class; wherein for an example the value CLa for the central venous pressure is represented by the equation:- CLa = (M (SA/1.8) S2)/ (P. K (S-D))-C c) evaluating means utilising a quantity KC to evaluate the ratio in the result CFSM from a measurement made by a common method in clinical practice, and, the result CFs from a measurement evaluated using the uncalibrated equation of this improved non invasive method; wherein the value KC is represented by the equation:- Kc = CFSM/CF5 d) evaluating means utilising a quantity DX to evaluate the value of the quantity Kc for an uncalibrated measurement; wherein the value of DX is represented by the equation:- i) DXH = KCH- (((HCLa-XCLa) (KcH-KCL))/ (HCLa-LCLa)) ii) DXL = KCL + (((XCLa-LCLa) (KcH-KCL))/ (HCLa-LCLa)) e) evaluating means utilising a quantity Kps the unit change of the value of the quantity KC relative to the unit change in the value of the range for a class from a school of each of the parameters in the equation required to evaluate the quantity CF5; wherein the value Kps is represented by the equation:- Kps = (KCH-KCL)/(QuH-QuL) f) evaluating means utilising a quantity DXL the net change of the DX value relative to the net change in the value of the quantity Kps for an uncalibrated measuremnt when the value of the quantity QuL is greater than the value of the quantity QuLx for a class from a school; wherein the value DXL is representd by the equation:- DXL = DX- ( (QuL-QuLx) Kps) g) evaluating means utilising a quantity DXH the net change of the DX value relative to the net change in the value of the quantity Kps for an uncalibrated measuremnt when the value of the quantity QuH is lower than the value of the quantity QuHx for a class from a school; wherein the value DXH is represented by the equation:- DXH = DX + ( (QuHx-QuH) Kps) h) evaluating means utilising the value of the quantity kn wherein kn is the result of having progressed in tandem where applicable in the DXL and DXH mode which are collectively used to adjust the value of the quantity DX and, otherwise, kn is equal to DX. i) means for obtaining measurements corressponding to a quantity Hgb, the haemoglobin concentration of the blood of a subject; j) means for obtaining measurements corressponding to a quantity U, the oxygen saturation of the blood of a subject; k) means for obtaining measurements corressponding to a quantity SA, the body surface area of a subject; 1) means for obtaining measurements corressponding to the pulse rate P of the subject; m) means for obtaining measurements corressponding to the systolic blood pressure S of the subject; n) means for obtaining measurements corressponding to the changes (S-D) in the pressure of the subject's blood during beating of the heart; o) means for obtaining measurements corressponding to the body temperature of the subject; p) evaluating means utilising a value R in the process of calibration of measurements of the said internal parameters; wherin the value R is represented by the equation:- R = (S-D) q) evaluating means utilising a value Pp in the process of calibration of measurements of the said internal parameters ; wherein the value Pp is represented by the equation:- p In a preferred embodiment, this improved method and apparatus of the invention filed in the aforesaid PCT/GB92/01041 document is calibrated for clinical use. Also, in clinical practice, it will make measurements of quantities in blood biochemistry, haematology, and blood gas in the process of non invasively evaluating the blood related internal parameters of blood organs of the subject, in clinical practice.

An example of the present invention is described in detail below with reference to the accompanying drawings in which:- Figure 1 shows a table of the tertiary key factors required to calibrate measurements of the plasma osmolarity W, the cardiac output CO, and the blood oxygen tension PO2; Figure 2 shows in a shematic tree, the varied pathway for deriving Kn.

Figure 3 shows in the form of a schematic table, the progress of a Figure 4 shows a graph of the value of the quantity Kc against the pulse and pulse pressure product for cardiac output and right ventricular pressure measurements ; Figure 5 shows a graph of values of the quantity KC against the blood pH; Figure 6 shows a graph of values of the quantity Tpv against predetermined measurement of the plasma total proteins concentration for a given haematocrit; Figure 7 shows the values of the quantity Wpv against predetermined measurements of the haematocrit for a given erythrocyte sedimentation rate; The following abbreviations are employed within the description:- SV = stroke volume of the heart ventricles CO = cardiac output P = the pulse rate of the heart CVP = the central venous pressure Y = the central venous pressure M = the convertion constant required for a change from a newtonian model to that of a non newtonian Q = the capacitance of the capacitance vessels pH = the loglo of the reciprocal of the blood hydrogen ion concentration PCO2 = the carbon dioxide tension of blood P02 = the oxygen tension of blood Sp = the mean systemic filling pressure PR = the total mean peripheral resistance of the circulation S = the systolic blood pressure D = the diastolic blood pressure R = the pulse pressure (S-D) Pp = the pulse and pulse pressure product (P. R) H = the output factor A = the measured packed cell volume (haematocrit) E = the measured erythrocyte sedimentation rate in mm/l sthr W = the measured plasma osmolarity ESR = the measured erythrocyte sedimentation rate in mm/hr T = the measured total plasma protein concentraton in g/l CLa = the class index LCP = the lower class pupil HCP = the higher class pupil XCP = the uncalibrated pupil LCLa = the predetermined class index of LCP HCLa = the predetermined class index of HCP XCLa = the class index of an uncalibrated measurement CFSM = the result of a measurement by a common method employed in clinical practice CF5 = the result of a measurement described by this non invasive method KC = ratio of CFSM to CF5 KCL = predetermined KC value for the LCP KCH = predetermined KC value for the HCP DX the Kn value, or the unadjusted value for Kn for an uncalibrated measurement DXL = the predetermined value of the quantity DX for the LCP DXH = the predetermined value of the quantity DX for the HCP PKF = the primary key factor SKF = the secondary key factor TKFn = the tertiary key factor Kps = the unit change in the value TKFn QuL = value of each of the parameters for the LCP used in the evaluation of CF5 QuH = value of each of the parameters for the HCP used in the evaluation of CF5 QuLx = value of each of the parameters used in the equation to evaluate an uncalibrated measurement QuHx = value of each of the parameters used in the equation to evaluate an uncalibrated measurement DXL = the progression of the DX value for an uncalibrated measurement DXH = the progression of the DX value for an uncalibrated measurement kn = the calibration constant for an uncalibrated measurement The organs of the body function with measurable predictability as in the pathogenesis of diseases and damage to the body organs. For an example, if a subject is starved of oxygen, he or she will die; and Mendel and Darwin showed that a trait is passed on from parent to child.

The organs of the body function with measurable frequency. For an example, there is frequency in the autoregulation of the heart, the rate of beating is regulated to meet with the metabolic needs of a subject; the function of the kidneys in the excretion of waste products of metabolism; and the eyes accommodate to focus upon a moving object.

The organs of the body function with calculated dependability as in the function of the brain and neural reflexes; there is the blood-brain barrier; there is a renal threshold for most of the substances excreted in urine ; the muscles will increase their bulk to accommodate increased workload; some diseases are self-limiting; and provided that their is no organ failure, life would be eternal.

In this improvement to the aforementioned PCT/GB92/01041 document, a method of calibration is used for all measurements described in this non invasive measurement of internal parameters of blood organs, and quantities in blood biochemistry, haematology and the blood gas of a subject, based upon the premise that the organs of the body function with measurable predictability, dependability, and frequency.

For any measurement, the total plasma protein concentration, T, is used as the first mode of classification, the Primary Key Factor, PKF. A school is defined by the range of plasma protein concentration, for an example:- a) equal to and greater than 40mg/1 but less than 50mg/l; b) equal to and greater than 50mg/l but less than 60mg/l; are classified as two different schools. Therefore, a measurement from a subject with a predetermined total plasma proteins concentration of 48mg/1 will belong to the equal to and greater than 40mg/1 but less than 50mg/l school, in the process of calibration of that measurement. The result of a clinical study which involved subjects who had measurements made by methods commonly employed in clinical practice, a databank is created with a catalogue of the PKF value of each subject, and for each measurement, listing the results and the value of each of the parameters which are required to make the corressponding uncalibrated measurements by an equation of this improved non invasive method of monitoring parameters of blood flow and quantities in blood biochemistry, haematology, and blood gas; the apparatus is able to place a measurement requiring calibration into a school, given the PKF value of the subject.

The value of a quantity CLa (the class index) is used as the Secondary Key Factor, SKF, a second mode of classification which enables a school to be divided into classes. For the process of calibrating the result of any measurement made by this improved non invasive method of monitoring parameters of blood flow and quantities in blood biochemistry, haematology, and blood gas, which both the method and the apparatus will henceforth be referred to as AMVOF5, the class index CLa is evaluated by the equation:- i) for all cardiac output measurements the CLa index is given by the equation:- CLa= 2P (S-D) K (SA/1.8)..... (1) ii) for all central venous pressure measurements the CLa index is given by the equation:- CLa = (M (SA/1.8) S2)/ (P. K (S-D))-C..... (2) iii) for all right ventricular pressure measurements the CLa index is given by the equation:- CLa= square root ( (SA/1. 8) K. P (S-D) (Y + C))/M,..... (3) iv) for all intracerebral pressure measurements the CLa index is given by the equation:- CLa = (M. S2)/ ( (SA/1. 8) K. H. r. U. pH)..... (4) v) for all right atrial pressure measurements the CLa index is given by the equation:- CLa = (Mp. S2)/ ( (SA/1. 8) K. U. P (S-D))-C..... (5) vi) for all intraocular pressure measurements the CLa index is given bv the equation:- CLa = ( (Fo/0. 24) + Pev) (K (SA/1. 8))..... (6) vii) for all haematocrit measurements the CLa index is given by the equation:- CLa = 3. Hgb..... (7) viii) for all erythrocyte sedimentation rate plasma osmolarity, and the molar equivalent concentration of a substance in a biological fluid measurements the CLa index is given by the equation:- CLa= Logl0 ((3. Hgb) í T) (8) ix) for all blood pH and blood carbon dioxide tension measurements the CLa index is given by the equation:- CLa = Sr2/ ( (Y + C) Sp (SA/1. 8) K)..... (9) x) for all stroke volume measurements the CLa index is given by the equation:- CLa= (S-D))/ (Q (SA/1. 8) K)..... (10) xi) for all pain index measurements the CLa index is given by the equation:- CLa = 100 (SVI/SV2) (11) xii) for all foetal distress index measurements the CLa index is given by the equation:- CLa = ( (Sm-Dm)/ (Qm (SAm/1. 8) Km))/Pf)..... (12) xiii) for all blood oxygen tension measurements the CLa index is given by the equation:- CLa = CO (Hgb/100) (U/100) 1.39..... (13) xiv) for all plasma total proteins measurements the CLa index is given by the equation:- CLa= Log10 (3. Hgb)..... (14) All the measurements in the clinical study had their CLa index evaluated using the above equations. The pupils in a class are paired off, in the order of their ascendancy in the value of the class index; for an example, if in the evaluation of CLa we have the following values:- of zero; A which is greater than zero but less than B; B which is less than C; C which is less than D; D which is lower than infinity (for the highest attainable value). The pairs take the form in the table below:- COLUMN 1 COLUMN 2 CLASS 1] Zero........................................................ ..................... A <BR> <BR> CLASS 2] A B<BR> <BR> <BR> <BR> <BR> <BR> CLASS 3] B........................................................... ....................... C<BR> <BR> <BR> <BR> <BR> CLASS 4] C........................................................... ....................... D<BR> <BR> <BR> <BR> <BR> <BR> CLASS 5] D........................................................... ....................... infinity The following pertains with reference to the above table:- i) the lower class pupil, LCP, has a value CLa which is lower for the pair than that of higher class pupil, HCP, to form a class from their school; ii) all the pupils in column 1 are the LCP, as those in column 2 are the HCP for each class; iii) a measurement which has been evaluated by AMVOF5 requiring calibration with a CLa value XCLa which is greater than A but less than B will belong to class 2 from its school; The value of the quantity CLa of all measurements made in the clinical study which involved subjects who had measurements made by methods commonly employed in clinical practice, which from henceforth will be referred to as standard measurements. are catalogued into their respective schools in the aforementioned databank to further define the measurement from a school by placement into a class. Using the princples of the SKF as described above all measurements evaluated by AMVOF5 will be placed into a class from a school.

Each result CFSM from a standard measurement is compared with its corressponding result CF5 evaluated by AMVOF5, the value of a quantity Kc can be expressed by the equation:- Kc = CFSM/CF5 (15) The predetermined Kc values, KCL for the LCP and KCH for the HCP of each measurement in a class from a school is catalogued into the databank; the value of the quantity Kc is used to adjust the value of the quantity CF5 so as to equal the CFSM which will lead to the equation CFSM = Kc CF5 Since each of the standard measurements made in the clinical study has in the databank the parameters required to make a corressponding measurement by AMVOF5 it can be assumed that the value of the quantity CF5 has been calibrated against its corressponding value of the quantity CFSM.

The value of the quantity Kc for an uncalibrated measurement made by AMVOF5 of a subject XCP with a predetermined PKF and with a value of the quantity XCLa, is evaluated utilising a quantity DX wherein DX is given by the equation:- DXH = KCH- (((HCLa-XCLa) (KcH-KCL))/ (HCLa-LCLa)) (16) in general, it is apparent that the value of the quantity DXH is the net change in the value of the quantity KCH relative to the ratio for the differences of the CLa value between the HCP and XCP against that of the HCP and LCP; and when the net change in the value of KCL is being evaluated, the quantity DXL is given by the equation DXL = KCL + (((XCLa-LCLa) (KcH-KCL))/ (HCLa-LCLa)) (17) The value of the parameters used in the evaluation of the quantity CLa the class index, QuL for the LCP and QuH for the HCP with predetermined values in the databank, and, QuX for an uncalibrated measurement may all have different values for the same parameter in the class. A third mode of classification, the Tertiary Key Factor, TKF, is employed in the databank. For an example in the measurement of the plasma osmolarity W, which is evaluated utilising the equation 60 W= kXg. lOO. Logl0 (3. Hgb) with reference to Figure 1, which lists the TKF required for plasma osmolarity W, cardiac output CO, and the blood oxygen tension PO2, the following pertains in defining a quantity TKF":- i) the surface area of the subject's body SA = TKF ii) the haemoglobin concentration Hgb = TKF2; iii) the erythrocyte sedimentation rate E = TKF3; vi) the body temperature of subject = TKF4; while being required by the method of calibration, there are some parameters TKF"in the measurement of plasma osmolarity which do not feature in the above equation.

The following are other examples of some TKF which do not feature in the uncalibrated equation for the measurement:- a) the subject's body temperature in the measurement of the blood gas, and the concentration of substances in biological fluids; b) the red and white cell blood count in the measurement of the haematocrit, and plasma total proteins concentration; c) the body weight in blood biochemistry, and haematology measurements.

Using predetermined values of the quantities QuL and QuH from each of the standard measurements in the clinical study, to constitute a range, a quantity Kps is derived for each TKFn in each class from a school, wherein Kps is evaluated utilising the equation Kps = (KCH-KCL)/ (QuH-QuL) (18) in general, it is apparent that the value of the quantity Kps is the unit change of the Kc value relative to the unit change in the TKFn for a class from a school. The Kps value for each TKF"in a class from a school is added to the databank.

When calibrating a measurement made by AMVOF5, the quantity Kps is utilised as follows:- i) a quantity DXL which is an adjustment of the value DX, based upon the value of QuX relative to its range that has been predetermined for the class from a school in the databank. When the value, QuL, the lower value of a TKFn range are higher than those recorded for the measurement, QuLx, i. e. the value QuLx is higher than QuX; the quantity DXL is evaluated utilising the equation:- DXL = DX- ((QuL-QuLx) Kps) (19) in general, it is apparent that the value of the quantity DXL is the net change of the DX value relative to the net change in the TKF"in a class from a school. The value of the quantity DX in the above equation is substituted by the value of the quantity DXLn the value of the preceeding DXL value, progressing in tandem, until all the QuLx value of the TKF"for the measurement have all been evaluated; ii) to continue the progress in tandem from the DXL and DXLn, the quantity Kps is used to evaluate a quantity DXH which is an adjustment of the value of DX based upon the value of QuX relative to its range that has been predetermined for the class from a school using standard measurements from the clinical study. When the value, QuH. the higher value of a TKF"range are lower than those recorded for the measurement, QuHx, i. e. the value QuHx is higher than QuX; the quantity DXH is evaluated utilising the equation:- DXH = DX + ((QuHx-QuH) Kps) (20) in general, it is apparent that the value of the quantity DXH is the net change of the DX value relative to the net change in the TKFn in a class from a school. The value of the quantity DX in the above equation is substituted by the value of the quantity DXHN the value of the preceeding DXH value, progressing in tandem, until all the QuHx value of the TKFn for the measurement have all been evaluated.

The value of the quantity kn is the result of having progressed in tandem, where applicable, in the DXL and DXH mode collectively to adjust the value of the quantity DX and, otherwise, kn is equal to DX; and in the following examples, to give a result for a measurement using AMVOF5 which will give a result expected from a standard measurement:- i) the quantity k6 is substituted by the value of the quantity kn in equation 23 for cardiac output measurements; ii) the quantity k8 is substituted by the value of the quantity kn in equation 28 for central venous pressure measurements; iii) the quantity k16 is substituted by the value of the quantity kn in equation 40 for pain index measurements; iv) the quantity k29 is substituted by the value of the quantity kn in equation 60 for plasma osmolarity measurements; v) the quantity k45 is substituted by the value of the quantity kn in equation 50 for haematocrit measurements; the schematic tree as shown in Figure 2 summarizes the pathways by which kn can be derived for an uncalibrated measurement.

It became apparent from the above clinical study used to create a databank for calibration, that the closer to zero the value of the standard error for a measurement, the greater is the number of classes from a school in the databank, to give results which are reproducible and dependable for use in the clinical management of a subject; in the following example:- <BR> <BR> a) the standard error for cardiac output measurements which are acceptable is +/- 300ml; and the number of classes found in a school in the databank are less than those for central venous pressure measurements; b) the standard error for central venous pressure measurements which are acceptable is +/-1. 5cmH2O ; and the number of classes found in a school in the databank are less than those for blood pH measurements; c) the standard error for blood pH measurements which are acceptable is +/-0.08.

In the form of a schematic table, Figure 3 shows the process of calibration of a measurement which belongs to a class with a CLa range (7) from a school (1) which has a PKF range of less than 40gm/1 plasma total proteins concentration; a subject with a predetermined plasma total proteins concentration (13) of36gm/l is entered into the school in the databank which has been created following the principles outlined above for calibrating measurements. The databank is stored into the read only memory ROM of the controller to follow the general configuration of the apparatus described in the aforementioned PCT/GB92/01041 document (reference line 36 of page 13 to line 3 from page 15); and access into the ROM is by the use of the microprocessor CPU. The CPU processes the value of each of the parameters measured for a subject, and evaluates for an example a calibrated measurement of the central venous pressure CVP as follows:- a measurement for calibration (2) is entered into a school (1) by its predetermined PKF value (13). The CLa value (6) of XCP is higher than the CLa (7) of LCP and lower than that for HCP, to place the uncalibrated measurement (2) into a class. The calibrated result KC (3) gives a DX value (4) for (2) using the equation DXH = KCH- ( ( (HCLa-XCLa) (KCH-KCL))/ (HCLa-LCLa)). The TKFn Of (2) are compared with their respective range from (1), the value QuLx (8) and QuHx (9) are utilised in tandem to adjust the DX value (4) using the constant Kps (10) for a TKFn to derive the value DXL (11) using the equation DXL = DX- ( (QuL-QuLx) Kps). And, to progress in tandem, the value of the quantity DXH is evaluated using the equation DXH = DXL + ( (QuHx-QuH) Kps). In the equation CVP = ( (ka (SA/1.8) M. S2)/ (P. K (S-D)))-C, the calibration constant k8 in the equation is substituted for the value of the quantity Kn.

It is generally accepted that there are three mechanisms which influence cardiac output. These are the contractility of the myocardium, the afterload and the preload.

Preload is determined by the initial length of the sarcomere, which normally is of some 2.2um. The contractile properties of the sarcomere are the protein bands of myosin (the A band), and actin (the I band), altogether constituting the contracting elements of the cardiac myofibril. The force of contraction is directly proportional to the resting sarcomere length. In severe cardiac disease where the heart may have become hypertrophic or dilated, the resting sarcomere lentgh is not more than 2.6um.

It is generally believed that the force developed by a contracting unit is directly proportional to the number of the crosslinks formed between the A and I bands of proteins, a function of the degree of overlap. A rise in the contractile force is observed when the I bands approximate, increasing the available crosslinks to the myosin band and, conversely, when the resting sarcomere length is stretched beyond the optimum, the reduced availability of crosslinks produce a decrease in the contractile force. The contractile unts of the myocardium function physiologically as a syncitium, which obeys the'All or None'response to a stimulus, i. e. a suprathreshold stimulus which is applied to an area of the heart will evoke a contraction of the entire myocardium, the spread of excitation from cell to cell depends upon the electrical conductance of the boundaries and, consequently, there is no propagation when the unit is dead, as found in myocardial infarction for an example.

The myocardium has the ability to change its strength of contraction for an observed resting length of its contractile units, the sarcomeres. This change of developed force (inotropy) for a given resting sarcomere length is defined as the state of contractility, or, the inotropic state of the myocardium. Contractility is influenced by changes in the metabolic and neurohumoral state of the subject. In practice, an index of contractility is given by the ventricular ejection fraction, the ratio of the stroke volume and the end-diastolic ventricular volume. When contractility of the heart is increased for a given diastolic volume. there is an increase in the stroke volume and work done by the ventricle. The Bowditch effect explains the positive inotropic effect observed with increased heart rate. It is generally accepted that the pulse pressure (the difference between the systolic and its diastolic pressure), corressponds to a volume increment which is some 80% of the total volume of blood, the stroke volume, ejected by the ventricle. For the heart which obeys the laws of heterometric autoregulation, the Frank-Starling law, cardiac output CO is the product of stroke volume SV and the heart rate P which leads to the expression CO = SV. P (equation 1 of PCT/GB92/01041 document) The failing heart does not obey the laws of heterometric autoregulation; there is generally an increased heart rate and a fall in stroke volume at rest, and, the response which is expected during exercise from an increased pulse rate is not in evidence, a state of chronotropic incompetence ensues.

Afterload is defined as the work done during ventricular ejection and, it is influenced by the peripheral resistance PR and the rheological properties of the circulation. It is generally accepted that in the failing heart, the stroke volume is dependent upon the afterload when contractility and preload are already compromised.

A Doppler ultrasound device is used in general practice to measure the afterload, a method based upon Laplace's law. Alternatively, the systolic, diastolic and mean blood pressure values are used as an index for the afterload, i. e. a high blood pressure generally reflects a high peripheral resistance.

By definition, the preload factor is the end-diastolic volume, represented by the pulse pressure, (S-D). The state of contractility is reflected by the output factor H H = P (S-D) (equation 13 of PCT/GB92/01041 document) and in this improved method, H = k5. P (S-D) K (21) wherein the quantity k5 reflects the peripheral resistance of the circulation; and if it is assumed that the rheological changes of the circulation is defined by the quantity K, representing changes in the haematocrit A, the depression of freezing point W, the total proteins concentration T and the erythrocyte sedimentation rate E, the quantity K is expressed by the equation K = (10/E) (43.2/A) (W/0.56) (T/8) (reference line 8 from page 10 to line 34 on page 13 of the aforementioned PCT/GB92/01041 document; and for topographical convenience the letter K used in this document replaces the original letter F, and, K bears no relationship to the K defined in claims 24,25, 49 and 50 of the aforesaid document being cited). applying the equation CO/k3 = P (S-D) = H (from line 17 of page 9 of the aforementioned PCT/GB92/01041 document), it can be assumed that changes in the preload, contractility, and afterload can be expressed using the equation CO is proportional to k3. k5. 2. P (S-D) K..... (22) To allow for more accurate results and facilitate measurements in this improved method, plasma osmolarity measurement has been subsituted for the depression of freezing point, accordingly the correction factor is expressed as 300/W; the plasma viscosity measurement, measured by any standard method is preferred to the zetacrit index to replace the erythrocyte sedimentation rate; also, studies have shown the importance of body surface area SA values in the adult and pregnant female.

Applying the principles for calibrating measurements as outlined above, the value for a quantity k6 which incorporates the constants from equation 22 for all cardiac output measurements made by AMVOF5 is evaluated using the equation CO = k6. 2P (S-D) K (SA/1.8)..... (23) The graph as shown in Figure 4 shows how in cardiac output measurements the value k6 change with changes in the pulse and pulse pressure product for a given pulse rate and pulse pressure, in subjects with cardiac function which do not conform with the laws of heterometric autoregulation ; and the degree of heart failure has been assessed clinically as grades 2 and 4 by the New York Heart Association functional classification; and in general, the cardiac output at rest is higher in grade 4 than it is for grade 2, which is consistent with experiences in clinical practice.

In the measurement of cardiac output in children, the following additional correction factors are required, as shown in the aforementioned PCT/GB92/01041 document lines 9 to 18 of page 21: wherein U is the arterial blood saturation, and pHb is the log of the reciprocal of the blood hydrogen ion concentration as the pH.

Applying the principles for calibrating measurements as outlined above, the value for the quantity k41 which incorporates the constants from equation 22 for all cardiac output measurements made by AMVOF5 is evaluated using the equation COk = k4l. 2P (S-D) K. U. pHb. (SA/1.8).... (24) In the measurement of cardiac output in the pregnant female, the following additional correction factors are required, as shown in the aforementioned PCT/GB92/01041 document line 35 of page 32 to line 9 of page 33: wherein L is the foetal length, pHu is maternal urinary pH, Sol ils the maternal urinary specific gravity, us is the maternal urinary glucose concentration, and fe is the maternal serum iron cocentration. Applying the principles for calibrating measurements as outlined above, the value for the quantity k36 which incorporates the constants from equation 22 for all cardiac output measurements made by AMVOF5 is evaluated using the equation COpu = k36.2P (S-D) K (SA/1.8) L. pHu. SGu. us. fe..... (25) In the measurement of the central venous pressure CVP by the method described in the aforementioned PCT/GB92/01041 document, a change from a Newtonian model to that of a non Newtonian was given by CVP = M. X (equation 10 of PCT/GB92/01041 document) while the emperical value of M is 10, M is not a constant with a fixed value; the value in parts represents a conversion ratio for the change from a newtonian model to that which is non newtonian. It is the thixotropy of blood which renders it a non newtonian fluid. Therefore, changes in the autoregulation of the systemic and capillary circulation are accommodated by a complentary change in the value of the quantity M. This improved method uses a quantity k7 to qualify the quantity M and, thereby, to account for the metabolic, rheological and neurohumoral factors regulating systemic and capillary blood flow, which leads to the expression CVP = ((k7. M. S2)/ (k5. P. K (S-D)))-C..... (26) In this improved method the quantities K and k5 are used to qualify the pulse and pulse pressure product, employing the principles outlined above, which leads to the expression CVP = ((k7. M. S2)/ (k5. K. P (S-D)))-C..... (27) Applying the principles for calibrating measurements as outlined above, the value for the quantity k8 which incorporates the constants from equation 27 for all central venous pressure measurements made by AMVOF5 is evaluated using the equation CVP = ( (ka (SA/1.8) M. S2)/ (P. K (S-D)))-C..... (28) The graph as shown in Figure 5 shows how in central venous pressure measurements the value kg change with changes in the blood pH for a given haematocrit and total plasma protein concentrations. The value of the quantity kn is approximately 1 when there is severe hypoproteinaemia and severe anaemia as shown by the curve A; which is consistent with the reduction of the normal thixotropic properties of blood.

In the measurement of central venous pressure in children, the following additional correction factors are required as shown in the aforementioned PCT/GB92/01041 document: wherein U is the arterial blood saturation, and pHb is the log of the reciprocal of the blood hydrogen ion concentration as the pH. Applying the principles for calibrating measurements as outlined above, the value for the quantity k37 which incorporates the constants from equation 27 for all central venous pressure measurements made by AMVOF5 is evaluated using the equation CVPk = ( (k37 (SA/1.8) M. S2)/ (K. U. pHb. P (S-D)))-C..... (29) In the measurement of the central venous pressure for the pregnant female, the following correction factors are required as shown in the aforementioned PCT/GB92/01041 document: wherein L is the foetal length, pHu is maternal urinary pH, SGu is the maternal urinary specific gravity, us is the maternal urinary glucose concentration, and fe is the maternal serum iron cocentration. Applying the principles for calibrating measurements as outlined above, the value for the quantity k38 which incorporates the constants from equation 27 for all central venous pressure measurements made by AMVOF5 is evaluated using the equation CVPpU = ((k38 (SA/1. 8) M. S2)/ (K. L. pHu. SGu. us. fe. P (S-D)))-C..... (30) Employing the principles of the use of constants k5 and k7 as expressed in equations 22 and 27, it is possible to calibrate the following measurements by AMVOF5 using a calibration constant in the equations which is substituted by the value of the quantity kn derived by the calibration method outlined above; where in the following:- i) in the measurement of left atrial pressure (Yp) for all adults, applying equation 26 of the aforementioned PCT/GB92/01041 document the value of the quantity kg is employed in the equation Yp = ((kg. Mp. S2)/ (U. K (SA/1. 8) P (S-D)))-C..... (31) ii) in the measurement of left atrial pressure Ypk for children, applying equation 30 of the aforementioned PCT/GB92/01041 document the value of the quantity k39 is employed in the equation Ypk = ( (k39. Mp. S2)/ (U. pHb. K (SA/1. 8) P (S-D))-C..... (32) iii) in the measurement of the right ventricular pressure Sr in all adults, applying equation 33 of the aforementioned PCT/GB92/01041 document the value of the quantity klo is employed in the equation Sr = Square root (klo (SA/1. 8) K. P (S-D) (Y-C))/Mr..... (33) iv) in the measurement of the right ventricular pressure Srk for children, applying equation 34 of the aforementioned PCT/GB92/01041document the value of the quantity k40 is employed in the equation Srk = Square root (k40 (SA/1.8) U. pHb. K. P (S-D) (Y + C))/Mr..... (34) v) in the measurement of the intracerebral pressure (Ib) for all age groups and the pregnant female, applying equation 43 of the aforementioned PCT/GB92/01041 document the value of the quantity k, l is employed in the equation Ib = (kl l. M. S2)/ ( (SA/1. 8) K. H. r. U. pH)..... (35) This improvement to the aforementioned PCT/GB92/01041 document will measure the stroke volume of the ventricles for all age groups and the pregnant female. Using the quantity, the fluid load or deficit factor Q to reflect capacitance Q = (M. S')/ (Y. P) (equation 24 of PCT/GB92/01041 document) The stroke volume SV is the volume of blood which is pumped out by each ventricle per each beat of the heart. In a heart which obeys the laws of heterometric autoregulation, a subject with a cardiac output CO and a pulse rate P, the stroke volume can be expressed by the equation SV = CO/P. For a subject whose heart does not obey the laws of heterometric autoregulation, the stroke volume can be evaluated as follows:- It is generally accepted that capacitance Q is directly proportional to the pusle pressure (S-D), and indirectly proportional to the stroke volume SV. It is possible to express stroke volume by the equation SV is proportional to (S-D)/Q For the heart which is non heterometrically autoregulated, as shown above, the quantities k5 and k7 are used to correct the quantities pulse and pulse pressure product and M respectively as in equations 22 and 27 above. Using a quantity k, which incorporates the constants k5 and k7, it is possible to express stroke volume by the equation SV = kl2 (S-D))/ (Q (SA/1.8) K)..... (36) Employing the principles of calibration as outlined above it is possible to calibrate the measurements of stroke volume by AMVOF5 using a quantity kl3 which incorporates the constant from equation 36 by the use of the equation SV = (kl3 (S-D))/ (Q. (SA/1.8) K)..... (37) This improvement to the aforementioned PCT/GB92/01041 document will measure the blood pH. The pH of a solution is the logarithym to the base ten of the reciprocal of the hydrogen ion concentration, [H+]. It is generally accepted that 99% of the pH of blood is attributable to the amount of carbonic acid in the ciculation, which in medical text, the Henderson and Hasselbach equation, is given as C02 + H20 = H2CO3 = H+ + HC03- and the pH is directly proportional to blood carbon dioxide tension pCO2. With reference to the aforementioned PCT/GB92/01041 document, page 33 lines 26 to 28, that the invention can be applied broadly and is not limited to the blood organs described, a quantity MSp which reflects the dynamic mean systemic filling pressure is used to derive pH i. e. in the derivation of the equation for the mean systemic filling pressure, the blood pH and the carbon tension of blood are correction factors required.

The mean systemic filling pressure is measured when the arterial and venous pressures come to an equilibrium when all flow in the systemic circulation ceases, at a point just before cardiac arrest when the arterial blood pressure falls to equal the venous pressure. Using a quantity k42, to account for the blood pH and carbon dioxide tension, using a quantity Sp, Msp can be expressed by the equation Sp is proportional to (k42. Sr2)/ ( (Y + C) P. U. K) Applying the principles for calibrating measurements as outlined above, the value for the quantity k14 which incorporates the constants in the above equation for Sp for all pH measurements made by AMVOF5 are evaluated using pH = (kl4. Sr2)/ ( (Y + C) P. U. Sp (SA/1. 8) K)..... (38) Similarly for the carbon dioxide tension of blood pCO the quantity pH in equation 38 is substituted for the carbon dioxide tension of blood; and using a quantity kl5 to replace the constant kl4, the calibrated carbon dioxide tension measurements by AMVOF5 are evaluated using the equation PCO2 = (kl5. Sr2)/ ((Y + C) P. U. Sp (SA/1.8) K)..... (39) The foregoing methods described for measuring the blood pH and carbon dioxide tension of blood apply individually to arterial and venous blood gas measurements of a subject.

Pain is defined by the International Association for the study of pain as,'An unpleasant sensory and emotional experience associated with actual or potential tissue damage'. It is generally accepted that the effects of pain upon the systemic circulation has been attributed mainly to the release of catecholamines. This improvement to the aforementioned PCT/GB92/01041 document will measure an index for pain. With reference to equation 36 SV = (kl2 (S-D) (Y + C) P)/ (10S2 (SA/1. 8) K) having substituted for Q, the fluid load or deficit factor, in the above equation; the following can be inferred:- a) the pulse and pulse pressure product, (P (S-D)) reflects the fluid displacement; b) Y is the central venous pressure; c) S is the systolic blood pressure; d) and P is the pulse rate.

The release of catecholamines will effect a change in the value of the quantities listed above, which will corresspond to a change in the volume of the stroke volume from a value SVl to SV2 which it is assumed will reflect a painful stimulus; and when SVI is greater than SV2, then, PA% will reflect the degree of pain free. Applying the principles for calibrating measurements as outlined above, the value for the quantity kl6 which incorporates the constant from equation 36, measurements of the Pain Index made by AMVOF5 are evaluated using the equation PA% = (kl6 (SVl/SV)) 100..... (40) wherein the standard measurements in the databank are accorded a range which are defined by the value of the quantity PA% to measure an index for pain which are graded for an example to be:- pain free; slight pain; moderate pain ; severe pain but tolerable; severe pain and not tolerable; and pain progressing to shock.

The intraocular pressure of the eye is defined as the balance between the rate of secretion of acqueous humour into the posterior chamber of the eye, and, the resistance to drainage from the anterior chamber. This improvement to the aforementioned PCT/GB92/01041 document will measure the intraocular pressure, the rate of drainage of acqueous liqour, and the pressure in the episcleral veins non invasively. From Grant's law, which has been based upon Hagen-Poiselle's law, the rate of drainage of acqueous liquor Fo is given by Fo = c (Poc-Pev) wherein c is a measure of the resistance to flow along the drainage route (the facility), Poc is the intraocular pressure, and Pev is the pressure in the episcleral veins.

Using a conversion factor kl7 to account for the change from the systemic circulation to that for the state in the circulation of the eye, applying equation 20 of PCT/GB92/01041 document it is assumed that the rate of drainage of aqueous liquor can be expressed by the equation Fo = (k17. 2M. S2)/ (Y + C)..... (41) and by the application of equation 27 of this document, and utilising a conversion factor k18 to account for the change from the systemic circulation to that for the state in the circulation of the eye, it is assumed that the pressure in the episcleral veins can be expressed by the equation Pev = ( (kl8. M. S2)/ (P (S-D)))-C (42) then, in accordance with Grant's law, the non invasive measurement of the intraocular pressure Poc by this improved method is evaluated by use of the equation Poc = ((k17. 2M. S2)/ (Y + C))/c) + ((klg. M. S2)/ (P (S-D)))-C)..... (43) Applying the principles for calibrating measurements as outlined above, the value for the quantity kl9 which incorporates the constants from equation 43 is used for calibrated measurements of intraocular pressure utilising the equation Poc = kl9 ( ( (2M. S2)/ (Y + C))/c) + ( (M. S2)/ (P (S-D)))-C).... (44) This improvement to the aforementioned PCT/GB92/01041 document will non invasively measure an index for foetal distress Ftd during pregnancy and childbirth by monitoring maternal parameters and the foetal heart rate. An account of the physioloical changes associated with pregnancy has been given from linel4 on page 30 to line 31 on page 32 of the aforementioned PCT/GB92/01041 document; and reference is also made to features in the circulation of a foetus line 30 on page 19 to line 20 on page 20, of the same text. It can be assumed that when there is no placental separation from the uterus the ratio of maternal blood flow rate into the placenta and foetal blood flow rate reaching the placenta is at an equilibrium which can be expressed by the ratio of their blood flow rate SVm/ (SVf x k20) = 1..... (45) wherein the quantity SVm is the maternal blood flow rate reaching the placenta per beat of the maternal heart; SVf is the foetal blood flow rate reaching the placenta per beat of the foetal heart; and k20 accounts for the differences in the pumping mechanism of the hearts and the state of the circulation. Substituting for stroke volume in equation 45, and by application of equation 36 above will lead to the expression ((k12(Sm-Dm))/(Qm(SAm/1.8)Km))/((k12.k20(Sf-Df))/(Qf(SAf/1.8 ) Kf)) = 1 ..... (46) and, since the only measurable non invasive quantity from the foetus is the foetal heart rate Pf, i. e. Qf = Mf. Sf2/Yf. Pf (equation 24 of the aforementioned PCT/GB92/01041 document), using a quantity k21 it is possible to express the foetal stroke volume by the equation SVf is proportional to ki.ko.Pf....(47) and, using for the foetal circulation a quantity k22, which incorporates the constants from equations 46 and 47, will lead to the expression (k22.Pf)=(Sm-Dm)/(Qm(SAm/1. 8) Km)..... (48) Applying the principles for calibrating measurements as outlined above, the value for the quantity k23 which incorporates the constants from equations 21 and 48, the Foetal Distress Range Ftr measurements made by AMVOF5 are evaluated using the equation Ftr=k23((Sm-Dm)/(Qm(SAm/1.8)Km))/Pf) .....(49) wherein the standard measurements in the databank are accorded a range which are defined by the value of the quantity Ftr to measure an index for Foetal Distress Ftd which are attributed the grades zero to five for an example to be:- grade 0 to classify a foetus not in distress and the grade 5 for foetal death.

This improvement to the aforementioned PCT/GB92/01041 document will measure the haematocrit, the erythrocyte sedimentation rate, the plasma osmolarity, and the concentration of a substance in a biological fluid (e. g the concentration of potasium ions in plasma) of a subject using predetermined values of the subject's total plasma protein concentration and blood haemoglobin concentration as follows:- The principles of calibrating a measurement outlined above makes it possible to make haematocrit measurements of a subject by use of predetermined values of the haemoglobin concentration using the known equation Haematocrit is proportoinal to (3 x Hgb) % applying the principles for calibrating measurements as outlined above, the value for a quantity k45 for haematocrit measurements made by AMVOF5 using predetermined measurements of the haemoglobin concentration A are evaluated using the equation A = k45 x (3. Hgb)..... (50) Before the Coulter analyser became popular, the standard method for measuring the packed cell volume PCV of blood is made by allowing a column of anticoagulated whole blood in a microtube to settle when a force greater than that of gravity is applied by a centrifuge to the column of the specimen; the height of the column of packed red cells is measured and expressed on the haematocrit scale as the packed cell volume of blood; there is separation of cells and plasma. Then, the volume of plasma, Vt, corressponding to a packed cell volume of A% is given by Vt = 100-A.... (51) Defining the correction factor Z for a total plasma proteins concentration as Z = 8/T from lines 10 to 12 of page 13 of the aforementioned PCT/GB92/01041 document, wherein, T is the subject's total plasma protein concentration, against the normal value of 8gm/100ml. It can be assumed that (100-43.2) will be equivalent to 8gm/100ml, wherein the normal haematocrit is 43.2%. Therefore, given a subject's haematocrit A%, the total plasma protein concentration Tpv can be expressed as Tpv is proportional to (8 (100-A))/56.8..... (52) Known factors which influence the erythrocyte sedimentation rate ESR are the prescence in blood of :- proteins; the packed cell volume which is associated with changes in erythrocyte volume, shape, size, density and deformity; rouleaux formation, the formation of erythrocyte aggregation; and the plasma viscosity. Using the correction factor B for erythrocyte sedimentation rate as B = 10/E from line 1 of page 12 of the aforementioned PCT/GB92/01041 document, wherein E is the subject's ESR, against the normal value of 10mm of the first hour of the Westergren method will lead to the expression Tpv is proportional to ( (100-A) E)/71..... (53) From the results of a clinical study, a graph of the value of the quantity Tpv was plotted against the corressponding predetermined total plasma proteins concentration which were measured by a known standard method; the graph as shown in Figure 6 showed an underlying trend that :- i) the quantity Tpv is indirectly proportional to the predetermined plasma protein concentration T ; ii) for a given value T, the value Tpv is indirectly proportional to the ESR; iii) for a given value T and ESR, the value Tpv is indirectly proportional to the packed cell volume PCV; iv) the non linear band of the curves are reduced as the erythrocyte sedimentation rate value falls; and it is increased as the packed cell volume rises; the result of clinical trials which applied the findings of the above study and equation 53, a value for plasma total proteins concentration using a quantity Tv is expressed by the equation Tv = 2. Loglo ( (3. Hgb) k24)..... (54) The constant k24 had a value of 1.408 for the population in the clinical study; and it will vary according to the prevalence of endemic infections, parasitic infestations and nutritional differences in various regions of the world. Applying the principles for calibrating measurements as outlined above, the value for the quantity k25 which incorporates the constant from equation 54, the plasma total proteins measurements made by AMVOF5 are evaluated using the equation T = k25.2. Loglo (3. Hgb)..... (55) As an alternative to equation 50, the AMVOF5 will make haematocrit measurements using predetermined measurements of the plasma total proteins concentration. The results of clinical trials showed that by substituting the haematocrit A for predetermined values of the plasma total proteins concentration T and using a constant k26 in equation 53 a value for the haematocrit using a quantity Av can be expressed by the equation Av = 20. Loglo (T k26).... (56) The constant k26 had a value of 1.408 for the population in the clinical study, and with the same properties as k24 above. Applying the principles for calibrating measurements as outlined above, the value for the quantity k26 which incorporates the constant from equation 56, the haematocrit A measurements using predetermined values of plasma total proteins concentration are evaluated using the equation A= k27. 20. Loglo (T) (57) Haemoglobin concentration measurements by AMVOF5 can be evaluated by the application of equation 57 using the equation Hgb = k48 ((20. LoglO (T))/3) wherein k48 is calculated by applying the principles for calibrating measurements as outlined above.

Osmolarity is defined as the molar equivalent of the number of molecular particles in one kilogram of water. An equation for plasma osmolarity measurements already exists in clinical practice which relies on measurements of the plasma concentration of the subject's sodium ions, blood glucose, blood urea-nitrogen concentrations, and corrected to the body temperature at time the sample of blood is made. Defining the correction factor F for plasma osmolarity of a subject as F = 0.56/W from lines 25 to 34 of page 12 of the aforementioned PCT/GB92/01041 document wherein W is the subject's plasma osmolarity against the normal value of 0.56 for the depression of freezing point. It is assumed that the normal plasma osmolarity is 300 mosmols/l. This improvement to the aforementioned PCT/GB92/01041 document will measure plasma osmolarity W as follows:- If the normal sodium ion concentration is 142mmol/l, it can be assumed that the contribution of sodium ion particles to the osmolarity of plasma of a subject with a normal plasma volume of (100-43.2), a quantity Wpv can be expressed by the equation Wpv is proportional to (142 (100-A))/56.8... (58) and by the application of the principles of equation 53 a quantity Wpv is expressed by the equation Wpv is proportional to ( (142 (100-A))/56.8)/ (10/E)..... (59) From the results of a clinical study, a graph of the value of the quantity Wpv was plotted against the corressponding predetermined plasma osmolarity which were measured by a known standard method; the graph as shown in Figure 7 showed an underlying trend that :- i) the value Wpv is directly proportional to the erythrocyte sedimentation rate ; ii) the value Wpv is indirectly proportional to the packed cell volume for a given erythrocyte sedimentation rate; iii) that for a given packed cell volume, the quantity Wpv is directly proportional to the erythrocyte sedimentation rate; iv) the value Wpv is indirectly proportional to the packed cell volume. and, the higher the range of erythrocyte sedimentation rate the greater is the degree of rise of Wv to the fall in packed cell volume; the result of clinical trials which applied the findings of the above study and equation 59, a value for plasma osmolarity using a quantity Wv can be expressed by the equation Wv = 100. Loglp ( (3. Hgb) k2§)..... (60) The constant k28 had a value of 58.8 for the population in the clinical study; and with the same properties as k24 above. Applying the principles for calibrating measurements as outlined above, the value for a quantity k29 which incorporates the constant from equation 60 for all plasma osmolarity measurements made by AMVOF5 are evaluated using the equation W= k29. 100. Log10 (3. Hgb).... (61) This improvement to the aforementioned PCT/GB92/01041 document will measure the concentration of a substance in a biological fluid of a subject as follows:- By the definition of the depression of freezing point, a depression of 1.86 °C is equivalent to 22.4atm of osmotic pressure (reference lines 27 to 28 page 12 aforementioned PCT/GB92/01041 document). In the following examples :- i) at physiological concentrations, sodium chloride does not dissociate completely; its fraction of the osmolarity of plasma is 1.86 mOsm/1 for each mEq/1 which is 1.86 * sodium ion concentration in plasma if the concentration of a substance which is totally or partially dissociated in a biological fluid is given by the value of a quantity Cs then its contribution to the osmolarity of the fluid is ii) a substance like urea which does not dissociate, its fraction of the osmolarity of plasma is calculated from the urea nitrogen; if the concentration of urea nitrogen is given by a quantity Cs, then its contribution to the osmolarity of the fluid is 1.86 x (Cs/2.8) the molecular weight of two nitrogen molecules is 28.

If the value of a quantity k30 is given by the ratio of the normal concentration of the substance in a biological fluid, and, the total osmolarity of the fluid, it can be assumed that the concentration of the substance Csv in a biological fluid with a predetermined total osmolarity Wbf is expressed by the equation Csv = k30-Wbf (62) If for an example the normal concentration of potasium ions in plasma of a population is 4mEq/1 with a plasma osmolarity of 300 centipoise, the constant k30 will have a value of 0.013. Applying the principles for calibrating measurements as outlined above, the value for a quantity k31 which incorporates the constant from equation 62 is used to measure molar equivalent concentration of a substance Csv in a biological fluid of predetermined osmolarity by AMVOF5 utilising the equation Csv = k31-Wbf (63) This improvement to the aforementioned PCT/GB92/01041 document will measure the erythrocyte sedimentation rate ESR as follows:- Defining the correction factor B for the erythrocyte sedimentation rate of a subject, E, as B = 10/E from lines 36 of page 11 to line 1 of page 12 of the aforementioned PCT/GB92/01041 document, and Substituting a quantity Ev for the quantity T in equation 53 will lead to the expression Ev is proportional to (71. Tpv)/ (100-A))..... (64) since the quantity Tpv has been shown to be:- i) indirectly proportional to the predetermined plasma protein concentration T; ii) that for a given value T, the value Tpv is indirectly proportional to the ESR; iii) that for a given value T and ESR, the value Tpv is indirectly proportional to the packed cell volume PCV; iv) that the non linear band of the curves are reduced as the erythrocyte sedimentation rate value falls; and it is increased as the packed cell volume rises; clinical trials showed that by using a quantity k32 which incorporates the constant from equation 64, a value for the quantity Ev can be evaluated by the equation Ev = k32. Loglo ((3 Hgb)/T) (65) The constant k-) had a value of 1.408 for the population in the clinical study; and with the same properties as k24 above. Applying the principles for calibrating measurements as outlined above, the value for a quantity k33 which incorporates the constant from equation 65, the erythrocyte sedimentation rate E measurements made by AMVOF5 are evaluated using the equation E = k33. Loglo ( (3. Hgb)/T)..... (66) From a graph drawn using the results of the clinical study, a conversion ratio is derived for predetermined values of the erythrocyte sedimentation rate ESR using the Westergren method, and, their equivalent plasma viscosity measurements PV made by the Harkness viscometer; the ESR is evaluated using predetermined values of the plasma viscosity in the equation ESR = (PV-1. 625)/0.00426..... (67) and, DPV = 1. 625 + (ESR * 0.00426)..... (68) This improvement to the aforementioned PCT/GB92/01041 document will measure the blood oxygen tension PO2 as follows:- applying the equation for the oxygen flux OF as given in medical texts will lead to the expression PO2 is proportional to ( (CO (Hgb/100) (U/100) 1.39))/OF applying the principles for calibrating measurements as outlined above, using the value of a quantity k34 to express the calibration factor which incorporates the constant from the above equation will lead the equation OFs = OFa. k34 wherein OFs is the oxygen flux measured by a standard method and the quantity OFa is the corressponding value of the oxygen flux measured by the application of the equation for cardiac output CO from the aforementioned PCT/GB92/01041 document.

Then by application of the equation for oxygen flux, a quantity Alfa is represented by the equation AoFa = CO (Hgb/100) (U/100) 1.39..... (69) If it is assumed that the quantity AoFa has a predetermined value of the blood oxygen tension OFs measured by a common method in clinical practice, wherein the value of the quantity AoFa is corrected by the value of the quantity k34, blood oxygen tension PO2 measurements made by AMVOF5 are evaluated by applying the equation 18 from above for the quantity Kps for a parameter TKFn the value of which is the oxygen tension PO2 range for a class from a school, using the equation OFa = QuH- ((KCH-KCL)/Kps) (70) where QuH is the oxygen tension of the HCP in the databank for a class in a school.

The SKF used is the value derived for the quantity AoFa And, the LCP in the databank for a class in a school is used as an alternative to equation 70 using the equation OFa = QuL + ((KCH-KCL)/Kps) (71) The foregoing method described for measuring the oygen tension of blood apply individually to arterial and venous blood gas measurements of a subject.

The measurement of weight of the critically ill is difficult, distressful to the patient and sometimes it is impossible. This improvement to the aforementioned PCT/GB92/01041 document provides a hydraulic bed which is calibrated to give body surface area of a subject using predetermined measurement of the height of that subject.

The method employs the principles of a basic laws of physics, that action and reaction are equal and opposite forces. With reference to the diagram as shown in Figure 8, a hydraulic bed 21 is placed on a smooth, flat and rigid surface 22. The entire body weight 27 of the subject induces a pressure 28 measured by a standard pressure guage, of the fluid 29 contained under pressure in the hydraulic bed 21. In a clinical study of a population, a databank is created utilising the predetermined body weight and height of each subject and the corressponding pressure induced upon the hydraulic bed. By the application of the principles of calibration as outlined above, the following pertains:- a) the primary key factor PKF utilised is the predetermined height uHp of the subjects; b) the secondary key factor SKF utilised is the pressure induced uPr by the predetermined subjects'weight; c) the tertiary key factor TKFn utilised is the predetermined weight uWp of the subjects; by the application of the principles of calibration as defined above, substituting the quantity uKps for the constant Kps, the value of the quantity uKps is evaluated utilising the equation uKps = (uPrH-uPrL)/ (uWpH-uWpL)..... (72) given the predetermined height of a subject uHx and the pressure uPrx induced upon the hydraulic bed, the unknown weight uWx of a subject is evaluated utilising the equation uWx = uWpH- ( (uPrH-uPrL)/Kps)..... (73) where uWpH is the weight uWp of the HCP in the databank for a class in a school.

The SKF used is the value derived for the uPr. The LCP in the databank for a class in a school is used as an alternative to equation 73 using the equation uWx = uWpL + ( (uPrH-uPrL)/Kps)..... (74) The unknown weight uWx of a subject is utilised to evaluate the body surface area SA using the known equation SA = w0. 425. hO. 725. 0. 00718 It will be apparent that the present invention can be applied broadly and is not limited to the blood organs described herein.