JP2657345B2 - Medical diagnostic apparatus and disease determination method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a medical diagnostic apparatus and a disease judging method, and more particularly to a medical diagnostic apparatus suitable for use in a medical diagnostic apparatus for judging a disease name from the amount and ratio of porphyrin in a subject. is there.

[0002]

2. Description of the Related Art As is well known, porphyrin is a general term for compounds having four pyrrole nuclei bonded thereto and widely exists in nature. Porphyrin in the human body is an intermediate molecule in the synthesis of hemoglobin molecules, myoglobin molecules, and heme, which forms several respiratory enzymes, and is synthesized in bone marrow and liver.

In the process of porphyrin synthesis, first, glycine and succinyl-CoA are condensed to δ-aminolevulinic acid, which is sequentially condensed to produce porphobilinogen. Then, two pairs of porphobilinogens combine to form porphyrin, and the porphyrin condenses to form heme.

In each of these reactions, one or more enzymes act as catalysts to regulate the progress of the reaction. Porphyrin has many isomers depending on the type and sequence of the side chain, and 14 types of free porphyrins detected from the human body have been confirmed.

FIGS. 7 (a) and 7 (b) show the structures of porphyrins. If a specific enzyme is damaged during the process of porphyrin synthesis, the reaction of the enzyme stops or the reaction speed slows down, causing abnormal accumulation of the substrate compound in the body. Reaction products are reduced.

[0006] Actually, the clinical metabolism society record: XX VI
I, 192, 1990, or LC Family
Jasco report: 22 (2), 5, 1987
As shown in, in healthy people, mainly uroporphy
rin (URO), coproporphyrin (C
OPRO) Types I and III, protoporph
Four kinds of yrin (PROTO) are detected in small amounts,
Others are detected in urine, blood and feces of patients with hereditary porphyria and various liver and blood disorders.

At present, porphyrin analysis methods performed in clinical laboratories and the like include, for example, Brush-Fisher, a simple urine porphyrin test method described in “Clinical Chemistry Analysis II (Tokyo Kagaku Dojin)”. Like the law,
Extract porphyrin and extract disease from the color tone and fluorescence of the extract.
There is a solvent extraction method to estimate the disease . However, in the above-mentioned solvent extraction method, sample preparation is complicated, and measurement is time-consuming, so that it is hardly analyzed in a general laboratory.

[0008]

Recently, Chrom has been developed.
atgr. Int. Symp. '89: 565-56
8, 1989, an automatic analysis method using high performance liquid chromatography (HPLC) has been reported, but the disease estimation technology has not yet been routinely developed.

[0009] By the way, many porphyrin metabolic disorders are also known to have acquired disorders besides genetic enzyme disorders.
For example, metabolic abnormalities are also observed in exposure to heavy metals and chemicals such as lead poisoning, blood diseases, and liver diseases. However, although information on the total amount of porphyrin can be obtained by an analytical method such as a conventional solvent extraction method, it has been difficult to measure the metabolic patterns of various porphyrins.

[0010] In addition, the content of various porphyrins can be accurately measured by HPLC, but a diagnostic device having a logical formula was required to estimate a disease from its metabolic pattern. An object of the present invention is to make it possible to estimate a disease of a test subject based on quantitative information and qualitative information of porphyrin in a subject.

[0011]

According to the medical diagnostic apparatus of the present invention, a logic for estimating a disease name based on a total amount of porphyrin present in a subject and a ratio of various porphyrins is determined to obtain a probability corresponding to the disease. Means, wherein said logical means comprises Form I and Form III isomers of coproporphyrin.
The method is characterized in that a probability corresponding to each criterion is provided according to the type and amount of various porphyrins to estimate a disease name.

Another feature of the medical diagnostic apparatus of the present invention is that input means for inputting data indicating the total amount of porphyrins present in the subject and the ratios of various porphyrins, Total amount calculating means for calculating the total amount of porphyrin in the subject from the data of the type and amount of porphyrin, and diseases in which porphyrin is extensively metabolized based on the value calculated by the total amount calculating means, In a disease that is metabolized and a disease that is not, a disease determining means for estimating the disease from a specific porphyrin amount and a ratio of the amount of each porphyrin,
The above-mentioned disease judging means comprises coproporphyrin type I and I
The present invention is characterized in that a disease is estimated by setting a probability corresponding to each criterion according to the type and amount of various porphyrins including type II isomer .

Further, the disease determination method of the present invention checks the porphyrin excretion pattern based on quantitative information, and qualitative information porphyrins in the subject, coproporphyrin
Porphyrin species including type I and III isomers of
The disease name is automatically determined based on the characteristics of the porphyrin excretion pattern on the basis of the porphyrin excretion pattern according to the criterion involving the probability according to the type and amount .

[0014]

In order to solve the above-mentioned problems, information obtained by HPLC or the like, that is, data on the type and amount of porphyrin in a subject is input and processed by the basic decision logic shown in FIGS. To output the processing result to the outside. Specifically, the total amount of porphyrin in the subject is calculated from the input porphyrin type and amount data to distinguish diseases in which porphyrin is extensively metabolized. The disease is estimated from the specific porphyrin amount and the ratio of each porphyrin, and is output to the outside. When estimating disease, coproporphyrin type I and I
The disease is estimated by a criterion with a probability depending on the type and amount of various porphyrins including the type II isomer .

The disease targeted by the medical diagnostic apparatus and the disease judging method of the present invention is congenital myeloid porphyria among congenital porphyrin metabolic disorders in urine analysis.
c Porphyria: CEP), atypical porphyria (Variegate Porphyria: V)
P), acute intermittent porphyria (Acute Int)
ermittent Porphyria: AIP),
Late-onset skin porphyria (PorphyriaCut)
anea Tarda: PCT), hepatic myeloid porphyria (Hepatoerythropoietic)
Porphyria: HEP), 5 types, acute lead poisoning (AL)
P), Dubin-Johnson syndrome (Dubin-J), which is one of the liver diseases and incurable diseases such as chronic hepatitis and cirrhosis.
ohson Syndrome: DJS), etc.
In addition, blood analysis revealed that the myeloid protoporphyria (ErythropoieticProtoporphosis)
yria: EPP), also blood diseases such as sideroblastic anemia estimated
Can be specified .

In healthy subjects, URO and COPRO are contained in urine.
Small amounts of type I and COPRO type III were detected,
ptacarboxylic porphyrin (H
EPTA), hexacarboxylic porp
hylin (HEXA), pentacarboxyl
Ic porphyrin (PENTA) is negligible.

The total amount is generally not more than 200 μg / 1, the ratio of COPRO I / COPRO III is 0.2 to 0.4, and the ratio to the total amount of COPRO III is 0.5 to 0.8. In patients with liver diseases such as chronic hepatitis and liver diseases such as cirrhosis, the total amount tends to increase slightly as compared with healthy persons, and URO and COPRO.
I increased, and COPRO I / COPR
The ratio of O III increases in the order of healthy subjects <chronic hepatitis <cirrhosis <liver cancer.

Dubin-Johnson syndrome DJS
Then, the total amount is almost the same as the healthy person, but COPR
The O I / COPRO III ratio tends to be even greater than in liver cancer. Therefore, COPRO
I // COPRO III ratio URO / COPRO III
From the ratio of I and the ratio of URO / COPRO III, it is possible to distinguish healthy subjects, liver diseases and DJS.

In inherited porphyrin metabolism disorders, a large amount of porphyrin is excreted in urine. The total amount is CE
P≫VP>AIP>PCT>HEP> EPP≫Patients with liver disease, healthy subjects, etc. In most cases, the dose is 500 μg / l or more, so that they can be easily distinguished from healthy subjects, liver diseases, etc. .

Comparing each porphyria, congenital myeloid porphyria CEP shows URO and COPRO.
Increase in type I, URO, C in atypical porphyria VP
Increase in OPRO III, PENTA and HEPTA, COPRO in acute intermittent porphyria AIP
III, URO and PENTA increase, PCT U
Increase in RO, HEPTA and PENTA, COPRO I, COPRO in hepatic myeloid porphyria HEP
III, URO and PENTA are increased, and the excretion pattern is characteristic and can be identified.

Also, in acute lead poisoning (ALP), porphyrin is excreted in a large amount in urine, and the pattern is CO
PRO III is very common. In addition, an increase in blood PROTO is observed in myeloid protoporphyria EPP.

According to the present invention, the disease name is determined based on the characteristics of the porphyrin excretion pattern in each of these diseases, and the type I coproporphyrin type
And a probability is provided in the criterion of the disease name according to the type and amount of various porphyrins including type III isomers ,
According to the present invention, a disease can be estimated from a porphyrin in a subject, and it can be used for screening or follow-up of a congenital porphyrin metabolism disorder or heavy metal poisoning such as lead, or a liver disease or a blood disease. Can be.

[0023]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The medical diagnostic apparatus of the present invention will be specifically described below according to one embodiment. As shown in FIG. 1, the basic configuration of the medical diagnostic apparatus 1 of the present embodiment includes a printer 3, a diagnostic processing device 4, a CRT 5, a floppy disk device 6, a keyboard 7, and the like.

The diagnosis processor 4 is provided for analyzing and processing the input data to estimate a disease, and determines a disease based on porphyrin type and amount data. Diseases are diagnosed by the diagnostic processing device 4.
The result of the determination , various data, and the like can be output by the printer 3 and can be displayed on the CRT 5.

The data on the type and amount of porphyrin are input directly from the keyboard 7 or provided from the high-performance liquid chromatograph apparatus 2. The high-performance liquid chromatograph device 2 is provided for separating each component from a sample, and includes, for example, a high-performance liquid chromatograph 10, a data processing device 11, a floppy disk device 12, and the like. FIG. 4 shows a liquid chromatogram of the porphyrin standard reagent. The six kinds of porphyrins excreted in urine are analyzed within 30 minutes.

The excrement from the human body as a sample varies depending on individual differences, gender, age, sample collection time, and the like. Therefore, in order to improve the accuracy of disease estimation , the judgment in FIGS. How much each porphyrin in addition to logic (COPROIII> COPRO I ×
10), or the ratio to the total amount.

Further, the criterion in Logistics <br/> click determined in consideration of the variation in the sample, it is desirable to have a certain width. In this embodiment, for example, the probability is 0% when the total amount Σ ≦ 400, and the probability is 100% and 400 <when the total amount Σ ≧ 500.
When the total amount Σ <500, a fuzzy function (linear function, trigonometric function, exponential function) that takes an intermediate value is defined, and the width of the judgment standard is adjusted by changing the selection of the fuzzy function and the setting of the domain. A fuzzy method was adopted. FIG. 5 shows the relationship between the judgment amount, the judgment probability, and the fuzzy function.

Thus, when the criterion varies greatly depending on the sample, the domain of the fuzzy function is set wider. In addition, in the case of a characteristic criterion for each disease,
By setting narrowly, the possibility of many diseases can be estimated. High Performance Liquid actual chromatographic analysis results of the urine sample, a disease by a medical diagnosis apparatus of this embodiment which is based on decision logic <br/> click shown in FIGS. 2 and 3
As a result of the estimation , the result is as shown in FIG.

The decision logic of FIG. 2 shows the decision logic when the total amount of porphyrin Σ ≧ 500. Sputum in this case, first of all, "there is suspicion of metabolic disorders of porphyrin"
An estimation of the case is made. Next, the component MA having the largest component amount
X1 is determined. In the decision logic of FIG.
RO, URO @ COPRO III, COPRO I,
The case where COPROIII is MAX1 is shown. As shown in FIG. 2, URO = MAX1 (URO>
MAX2), then COPRO I, COPRO I
III, HEPTA is determined as the second largest component amount MAX2.

If COPRO I is MAX2, COPRO I COPRO III is determined, and if so, it is estimated to be “CEP”. Also, COPRO
When III is MAX2, COPRO III> C
OPRO I is determined, and if so, is estimated to be "VP". Further, when HEPTA is determined to be MAX2, it is estimated to be “PCT”.

Also, URO @ COPRO III = MA
If X1 is determined, PENTA> MAX3 is determined, and in that case, “AIP” is estimated . Further, if COPRO I = MAX1, it is estimated as “HEP”, and if COPRO III = MAX1, it is estimated as “ALP”.

When the total amount of porphyrins = Σ <500, the determination logic is as shown in FIG. In this case, first, COPRO I = MAX1, COPRO I
I ≒ COPRO III, COPRO III = MAX
1 is determined. When COPRO I = MAX1, 1.1 <COPRO I / COPRO II
I is determined. Then, if so, then Σ> COP
A determination is made for RO III * 5 and Σ ≦ COPRO III * 5. In this case, Σ> COPRO III
If * 5, it is estimated to be "DJI". Also, Σ ≦ CO
In the case of PRO III * 5, it is estimated to be "liver cancer".

Further, COPRO I @ COPRO I
If it is determined that II and COPRO III = MAX1, 0.8 <COPRO I / COPRO III ≦
1.1, 0.5 <COPRO I / COPRO III
≦ 0.8, COPRO I / COPRO III ≦ 0.
5 is determined. And 0.8 <COPRO
If it is determined that I / COPRO III ≦ 1.1, “cirrhosis”, 0.5 <COPRO I / COPRO III ≦
If it is determined to be 0.8, it is estimated to be "chronic hepatitis". Also,
If COPRO I / COPRO III ≦ 0.5, it is estimated to be “healthy person”.

As shown in FIG. 6, CEP, VP, AIP, PCT, H, which excrete a large amount of porphyrin in urine,
EP and ALP were estimated with high probability. In addition, although the amount of excretion in urine is small, DJ whose pattern is characteristic
The judgment probability of S was also high. On the other hand, since the pattern of liver disease gradually changes depending on the degree of the disease, the probability of judgment is slightly lower than that of others, but it is sufficiently applicable to temporary screening and follow-up.

[0035]

As described above, according to the present invention,
Estimation of diseases that cause abnormal porphyrin metabolism by processing information on the total amount of porphyrins present in the subject and the information on the ratios of various porphyrins using a judgment logical formula to determine the disease of the test subject In addition, it is possible to provide a disease determination system capable of monitoring the function of an organ such as the liver. When estimating disease, coproporphyrin type I and
By providing a probability in the criterion for determining a disease according to the type and amount of various porphyrins including porphyrins including type III and III variants, the disease can be estimated more accurately.

[Brief description of the drawings]

FIG. 1 is a configuration diagram showing one embodiment of a medical diagnostic apparatus of the present invention.

FIG. 2 is a decision logic diagram which is the basis of the present invention.

FIG. 3 is a decision logic diagram which is the basis of the present invention.

FIG. 4 is a high performance liquid chromatogram of a standard sample.

FIG. 5 is a diagram showing a relationship among a judgment amount, a judgment probability, and a fuzzy function.

FIG. 6 is a diagram showing an example of a result of disease estimation performed according to the present invention.

FIG. 7 is a diagram illustrating the structure of porphyrin.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Medical diagnostic apparatus 2 High-speed liquid chromatograph apparatus 3 Printer 4 Diagnostic processing apparatus 5 CRT 6 Floppy disk 7 Keyboard 10 High-speed liquid chromatograph 11 Data processing apparatus 12 Floppy disk

Continued on the front page (51) Int.Cl. ⁶ Identification number Agency reference number FI Technical display location G01N 30/00 G01N 30/00 Z 33/493 33/493 A 33/52 33/52 C (72) Inventor Toshio Koike 1618 Ida, Nakahara-ku, Kawasaki City Nippon Steel Corporation Advanced Technology Laboratory (72) Inventor Hiromasa Nomura 20-1 Shintomi, Futtsu City Nippon Steel Corporation Technology Development Division (72) Inventor Hisashi Yanagisawa Tokyo 2-20-15 Shinkawa, Chuo-ku, Tokyo Nippon Steel Information & Communication Systems Co., Ltd. Steel Systems Division, Science and Technology System Department (56) References JP-A-55-75651 (JP, A)

Claims (4)

(57) [Claims] 1. Coproporphyrin present in a subject
Porphyrin species including type I and III isomers of
A logic means for obtaining a probability corresponding to the disease according to the type and amount and estimating the disease name is provided. The logic means establishes a probability corresponding to each criterion according to the type and amount of various porphyrins and provides a disease name. A medical diagnostic apparatus characterized by estimating the following. 2. The medical diagnostic apparatus according to claim 1, wherein the subject is urine or stool excreted from the body, or blood collected from the body. 3. An input means for inputting data indicating the total amount of porphyrin present in the subject and the amount ratio of various porphyrins, and the total amount of porphyrin in the subject based on the input data on the type and amount of porphyrin. A total amount calculating means for calculating, a disease in which porphyrin is extensively metabolized based on the value calculated by the total amount calculating means, in a disease in which a large amount is metabolized and a disease in which it is not, a specific amount of porphyrin and Disease determining means for estimating a disease from the amount ratio of each porphyrin, wherein the disease determining means comprises coproporphyrin type I and coproporphyrin
A medical diagnostic apparatus, wherein a disease is estimated by providing a probability corresponding to each criterion according to the type and amount of various porphyrins including type II isomers . 4. A porphyrin excretion pattern is detected based on quantitative and qualitative information of porphyrin in a subject, and the type I and III isomers of coproporphyrin are detected.
A disease judging method characterized by automatically judging a disease name based on the characteristics of the porphyrin excretion pattern based on a criterion with a probability depending on the type and amount of various porphyrins .