[Respiratory function tests--current and future perspective].

The apparatus for the respiratory function test have recently made a great progress and become very easy to handle owing to the development of computer technology and medical ordering system. However, the respiratory function tests depend its result on the cooperation of patients. Thus, it is important for the medical technician to obtain the maximum efforts and cooperation of the patients in the testing. In the sense, the standardization of the testing should be done urgently regarding procedures, softwares, hardwares and maintenance of apparatus. In the future perspectives, we would like to emphasize following 3 points. First, more noninvasive and sophisticated testing methods and instruments should be developed, since the patients' age will become more and more old and vigorous active cooperation may not be possible for the assessment of respiratory function. The testing for the transplantation of lung should also be developed. Second, the development of screening test and its performance for the routine medical check for the local inhabitants have been important for the early detection, treatment, and follow up of respiratory diseases. Finally, the medical technician should be prepared so that the testing is available when it is needed.

Lipoprotein(a) concentrations in healthy subjects in the Dominican Republic. Comparison with Japanese.

Previous studies have shown that serum concentrations of lipoprotein(a) [Lp(a)] are markedly different among different ethnic groups. We examined the serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol and Lp(a) in apparently healthy subjects aged 20-69 years in Japan (n = 865) and the Dominican Republic (n = 1,893). Dominicans had significantly lower levels of total cholesterol and HDL cholesterol than Japanese. The distribution of Lp(a) concentrations were markedly skewed towards low levels in both Japanese and Dominicans. However, the mean Lp(a) concentration in Dominicans was approximately 2 times higher than in Japanese (21.7 +/- 23.7 vs 12.3 +/- 15.9 mg/dl, p < 0.001). This is possibly because the majority of Dominicans are of mixed Negroid and European blood.

[Standardization of serum lipid examination: an attempt in Oita].

There is an obvious difference in currently available clinical laboratory data between hospitals. With the advent of information systems, the clinical laboratory information in the future must be standardized so that it can be used in medical treatment and health control throughout the life patients time. Establishing publicly acknowledged standards is essential for standardization to be translated into practice. The standards for clinical laboratory examination in Japan are approved by consensus in the Japanese Committee for Clinical Laboratory Standards (JCCLS). However, standards have yet to be established for most laboratory examinations. This poses is a major obstacle in promoting the standardization. Standardization should be implemented carefully with consideration of the worldwide trend. That is probably the reason why the consultation and approval at JCCLS have been delayed, but it is hoped that standards will be established as soon as possible. The committee for quality control survey in Oita Medical Association organized a Lipid Unit of the Sectional Committee for Standardization in 1994 and has since implemented standardization according to the lipid standardization program of the U.S. Centers for Disease Control and Prevention (CDC) with some modifications. Measures for improvement have been adopted for a trial period in parallel with four surveys, and in September, 1995 all 9 hospitals passed the standardization test performed on the basis of the CDC provisions for certification. The Oita Medical Association plans to expand the lipid standardization to all parts of the prefecture using the trial of standardization by the Lipid Unit as a model.

Significance of urinary fibrin/fibrinogen degradation products (FDP) D-dimer measured by a highly sensitive ELISA method with a new monoclonal antibody (D-D E72) in various renal diseases.

To diagnose the abnormalities of coagulation-fibrinolysis in various renal diseases, we developed a new monoclonal antibody (D-D E72) against fibrin/fibrinogen degradation products D-dimer (FDP D-dimer) and established a highly sensitive enzyme-linked immunosorbent assay (ELISA) for its measurement. FDP D-dimer was assessed in 102 patients with various renal diseases, and the following results were obtained: 1. The mean level of urinary FPD D-dimer in 32 normal controls was 0.69 +/- 0.60 ng/ml (mean +/- SD). 2. The level of urinary FDP D-dimer was significantly higher in primary nephrotic syndrome group (NS), chronic renal failure group (CRF) and in the group of diabetic nephropathy (DM) than in the control group. However, no difference was observed in the level of urinary FDP D-dimer between non-nephrotic chronic glomerulonephritis group (CGN) and control group. 3. No significant correlation was revealed between D-dimer and urinary protein in CGN and NS groups. These results suggest that in addition to plasma filtration the urinary FDP D-dimer in NS, CRF and DM may be also related to abnormalities of secondary fibrinolysis in intra-glomerular fibrin deposits.

Significance of urinary fibrin/fibrinogen degradation products in renal diseases measured by a highly sensitive ELISA.

The urinary fibrin/fibrinogen degradation products (FDP), as sensitive indicators of various renal disorders, have been measured by several methods. For their determination, a new and highly sensitive enzyme-linked immunosorbent assay not requiring the urine concentration has been developed. The study comprised 42 patients with nonnephrotic chronic glomerulonephritis (CGN), 23 patients with primary nephrotic syndrome (NS), and 29 healthy adults. The results were as follows: (1) the content of urinary FDP in normal subjects was 10.30 +/- 9.08 ng/ml; (2) the mean level of urinary FDP in both CGN and NS groups was significantly higher than in normal subjects; (3) in the CGN group itself there was a tendency for an increase of urinary FDP during more active forms of the disease, and (4) there was a significant correlation between urinary FDP and urinary protein in the CGN group, whereas no correlation was observed in the NS group. These results suggest that the major part of urinary FDP in the CGN group derives from the increased filtration, while its origin in the NS group is not related to increased filtration only, but may also have involved intraglomerular coagulation abnormalities. The newly developed enzyme-linked immunosorbent assay can detect urinary FDP levels lower than 3.9 ng/ml. Therefore, this method can be of great value in determining the degree of abnormalities of intraglomerular coagulation and fibrinolysis in renal diseases.

[Significance of urinary fibrin/fibrinogen degradation product (FDP) D-dimer measured by highly sensitive ELISA method with a new monoclonal antibody (D-D E72) in various renal diseases].

In order to clarify the abnormalities of the coagulation and fibrinolysis system in patients with various renal diseases, we produced a new monoclonal antibody for FDP (fibrin/fibrinogen degradation product) D-dimer (D-D E72). We also established a new highly sensitive method of enzyme-linked immunosorbent assay (ELISA) for urinary FDP D-dimer using this monoclonal antibody. The urine from 110, patients with various renal diseases was investigated for the FDP D-dimer. The results are summarized as follows: 1) Urinary FDP D-dimer in normal subjects was 0.69 +/- 0.60 ng/ml. 2) The level of urinary FDP D-dimer in patients with primary nephrotic syndrome and in patients with chronic renal failure was significantly higher than that of normal subjects, whereas the urinary FDP D-dimer levels in patients with diabetes mellitus were higher than those of normal subjects. 3) In the CGN and NS groups there was a tendency for an increase in the level of urinary FDP D-dimer in more active forms of the disease. 4) A significant correlation between urinary FDP D-dimer and urinary protein in the CGN and NS groups was demonstrated. 5) In all of the renal diseases investigated in this study, the ratio of urinary FDP D-dimer to total FDP was less than 4%.

[Molecular marker for detecting hypercoagulable state].

We measured various coagulable factors and molecular markers in plasma and serum in the disease group including DIC, DIC suspect, thrombosis, acute myocardial infarction, angina pectoris, sepsis, malignant tumor and type II diabetes and the healthy subject group, and surmised the intravascular coagulative-fibrinolytic activity in each disease group compared with the healthy group. Additionally we selected parameters useful for early detection of the pre-thrombotic state and hypercoagulable state. As a result, of the parameters for the coagulative system, those considered useful were the assay of soluble fibrin monomer complexes using the synthetic substrate (FM.Oita), assay of soluble fibrin monomer complexes using HPLC(SFMC.Oita) and thrombin-anti-thrombin III complex (TAT) in this order. Of the parameters for the fibrinolytic system, those considered useful were FDP assay using ELISA (FDP.Oita) and plasmin-alpha 2 plasmin inhibitor complex (PIC). This FDP.Oita had a considerably high detection sensitivity compared with the FDP assay (Diayatron Co.) using the latex photometric immunoassay which has been commercially available. When measurement was made with plasma and serum in the subject disease group as the sample by the high sensitivity assays mentioned above, it was made clear that both the coagulative activity and fibrinolytic activity are increased, albeit with some differences in intensity, in all the disease groups compared with the healthy group. In order for the hypercoagulable state and pre-thrombotic state to be detected, it is important to know the balance between the coagulative activity and fibrinolytic activity. According to the results of the present experiment, a significant directly proportional correlation was recognized between FM.Oita and FDP.Oita and between TAT and FDP.Oita. Therefore, examination of these ratios will be a more detailed indicator of coagulative-fibrinolytic activity than the TAT/PIC ratio, PAI-1/TPA ratio and ATIII/alpha 2 PI ratio hitherto in use. If useful molecular markers such as FM.Oita are measured over time in various cases and these data are compiled and analyzed statistically, it will not be long before the criteria for the hypercoagulable state and pre-thrombotic state are established.

[Significance of urinary fibrin/fibrinogen degradation products (FDP) measured by highly sensitive ELISA method in various renal diseases].

In order to clarify the abnormalities of intra-glomerular coagulation and fibrinolysis in patients with various renal diseases, urinary fibrin/fibrinogen degradation products (FDP) have been examined by several methods. We established a highly sensitive new method of enzyme-linked immunosorbent assay for urinary FDP. The results were as follow: 1) The mean +/- SD of urinary FDP in normal subjects was 10.30 +/- 9.08ng/ml. 2) The urinary FDP levels in chronic glomerulonephritis, nephrotic syndrome and chronic renal failure patients were significantly higher than normal subjects, and the levels in SLE, Alport's syndrome patients were higher than normal subjects. 3) The urinary FDP levels were a little bit higher in the patients with proliferative glomerulonephritis than in chronic glomerulonephritis patients with minor lesion or membranous nephropathy. 4) There was significant correlation between urinary FDP and urinary protein in chronic glomerulonephritis, while there was no correlation in nephrotic syndrome. 5) There was no correlation between urinary FDP and intra-glomerular fibrin deposits examined by immunofluorescent study in chronic glomerulonephritis, while in nephrotic syndrome, there were high levels of urinary FDP in the positive fibrin deposits cases. These results suggested that the most of the part of excretion of the urinary FDP in chronic glomerulonephritis is associated with the filtration of blood FDP to urine through the glomerular basement membrane, while in the nephrotic syndrome cases the origin of urinary FDP is related to the filtration and/or the intra-glomerular coagulation abnormalities.

[Studies on molecular markers for hemostasis and thrombosis in various renal diseases].

In order to clarify the abnormalities of blood coagulation and fibrinolysis in patients with various renal diseases, some molecular markers for hemostasis and thrombosis were examined in comparison with those of the patients with disseminated intravascular coagulation. The results were as follows: 1) PIC was significantly higher in the patients with CGN, NS, SLE, HD and DIC than normal subjects. 2) TAT was significantly higher in the patients with CGN, NS, HD and DIC. 3) SFMC was significantly higher only in the patients of DIC. 4) FDP and FDP-E were significantly higher in the patients with HD and DIC. 5) D-dimer was significantly higher in the patients with CGN, CRF, HD and DIC. These results suggested that the abnormalities of blood coagulation and fibrinolysis in patients with various renal diseases are relatively mild, and situated between the normal subjects and patients with DIC.

[Carcinoembryonic antigen, alpha-fetoprotein and hepatoma alkaline phosphatase in gastric carcinoma].

Reported here is a 38-year-old woman who had a gastric cancer accompanied with liver metastasis. Abnormal serum levels of a carcinoembryonic antigen, alpha-fetoprotein, and an alkaline phosphatase isozyme were observed persistently after a gastrectomy. The properties of this alkaline phosphatase isoenzyme were identical to a hepatoma alkaline phosphatase type. Histologic findings of the stomach revealed a poorly differentiated adenocarcinoma. The patient died on the 180th postoperative day.