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A 79-year-old female was diagnosed with epilepsy because she experienced loss of consciousness twice in January and February and then had a seizure in June 2016. She was treated with 800 mg sodium valproate (sustained release). After 3 days, she experienced loss of appetite, and more than 3 days later, disturbance of consciousness. Serum valproic acid (VPA) concentration was 128.3 μg/ml and serum ammonia was 404 μmol/l. Cerebral edema and status epilepticus occurred. Severe neurological dysfunction remained, even after treatment with continuous hemodiafiltration and levocarnitine. VPA is widely used for the treatment of generalized epilepsy. VPA-induced hyperammonemic encephalopathy is a rare but serious adverse event of VPA. Thus, we must pay attention to serum ammonia levels when using VPA, even VPA monotherapy.

Organic-inorganic hybrid molecules can exhibit biological activities by controlling the activities of their individual components. These molecules can be applied as seed/lead compounds in drug development, and can be used as molecular probes in chemical biology for the elucidation of the molecular mechanisms of biological systems. In this review, we introduce copper diethyldithiocarbamate (Cu10), a copper complex, as a compound that activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces metallothionein, which are the key cellular defense factors against toxic metals and oxidative stress in vascular endothelial cells. It was found that neither the complexes with the same ligand and other metal ions (including zinc and iron) nor the ligand alone was inactive. Therefore, both copper ion and the ligand of Cu10 are essential components for the biological functioning of the complex. In addition, Cu10 may be useful in clarifying the molecular mechanism underlying metallothionein induction in vascular endothelial cells.

Organometallic compounds and complexes possibly show novel bioactivities unprecedented with organic molecules that consist of C, H, O, and N atoms. We have already reported that an organoantimony compound selectively induces the expression of perlecan, a large heparin sulfate proteoglycan, in cultured vascular endothelial cells. Perlecan consists of a core protein with Mr of approximately 400 kDa and three anticoagulant heparan sulfate glycosaminoglycan chains. However, little is known about the molecular mechanisms of perlecan expression in endothelial cells. Since an organoantimony compound induces the expression of perlecan, we prepared a variety of its derivatives and tried to identify the binding proteins for the organoantimony compound by the drug affinity responsive target stability method, a negative selection method to identify the target proteins. As the results, we found glucocoriticoid receptor as binding protein of the organoantimony compound, which mediates the expression of perlecan in endothelial cells.

Metabolic markers of bone are common clinical parameters for the evaluation of the pathophysiologic conditions and efficacy of the treatment, although they are not helpful for differential diagnosis of osteoporosis. The guideline published officially is helpful for practitioners and non-experts in the field. The distributions of urinary NTX and bone specific alkaline phosphatase are essentially same between primary osteoporotic postmenopausal women less than 70 years old and those over 70 years. No differences were found in the other metabolic markers between these groups. Although clinical evidence for patients over 85 years old is not enough, we do not have to think of age in the clinical application of metabolic markers of bone, if renal functions are within normal ranges.

Time-course changes of serum PTH and various bone markers were compared after injection of 1alpha,25 (OH)(2)D(3) with that of 22-oxacalcitriol (OCT) in hemodialysis patients. Five patients (M/F; 3/2, mean ages of 61.6 years) were enrolled into the present study. Oral administration of vitamin D(3) derivatives was stopped at least one week before initiation of vitamin injection. After 1 week of single intravenous injection of OCT (5 microg), 1alpha,25 (OH)(2)D(3) (0.5 microg) was followed. Serum levels of intact PTH, intact osteocalcin, bone alkaline phosphatase, cross-linked N-telopeptides of type I collagen, calcium, and phosphate were measured before, 24h, and 48 h after injections of vitamin D(3) derivatives. Significant difference did not exist in time-course changes of serum PTH, any of bone markers, calcium and phosphate between after OCT and 1alpha,25 (OH)(2)D(3) injection. In conclusion, the present study may not support the presence of significant direct effect of vitamin D(3) derivatives on bone metabolism in hemodialysis patients.

High-impact or weight-bearing physical activities have positive effects on bone mass gain in children and adolescents from the findings of the physical activity intervention trials for them. These physical activity trials have been relatively short term in research design and some of the intervention trials had small numbers of subjects. Significant benefits on bone mass gain in children and adolescents were observed in almost all studies concerning physical activity intervention trials, although there was considerable variability in magnitude. The discrepancies in findings might relate to the characteristics of participants (sex, age, maturity); the characteristics of the intervention (intensity, frequency, duration); and the bone region assessed (cortical vs. trabecular). In current research on bone mass gain in children and adolescents, there is a lack of data about the effects of different types of physical activity, the long-term effects of physical activity during growth, and the interaction between pubertal development and physical activity. The results of this study call for a further accumulation of evidence about the effects of physical activity to promote bone health in children and adolescents.

The clinical use of drugs, which modestly increase bone mineral density, but have sufficient effects on the fracture prevention comparable to bisphosphonates, focuses on the research of the quality of the bone. Clinical investigations using micro CT, Fourier transform infrared imaging spectroscopy, quantitative computerized tomography, and/or other new modalities which support bisphosphonate treatment do not show any quality problems of the bone. In the clinical setting, evaluation of bone quality is very limited, even in the evaluation of patients treated with bisphosphonate, except evaluation by the changes of metabolic markers of bone. The new modalities such as low radiation-dose CT, sensitive MRI or ultra sonography are expected for the clinical evaluation of the changes of bone quality.

In the evaluation of external quality control survey, the mean value of peer group has been using as the target value generally. However, there are some arguments about whether the mean value shows the true value of survey sample. In 1992 National Federation of Industrial Health Organization(NFIHO) established the committee for reference target value and studied the determining of reference target value. In 1993 NFIHO started the evaluation by the reference target value determined by the committee. In 1996 committee for external quality control survey of Japan Medical Association (JMA) started the evaluation by adjusted mean value of peer group. In 1999 JMA established the sub-committee for target value and published the study report in 2000. By using the result from the above two associations, I have studied the possibility of the evaluation by target value. I concluded as follows. 1) The good agreement was seen between the target values and the mean value of peer group. 2) The poor agreements were seen in some anaytes. 3) By increasing the number of laboratory in which the traceability is being confirmed, the better agreement will come to be seen between the target value and the mean. 4) To determine the target value, we need the long-term maintenance of laboratory performance and the consumption of large energy. 5) As for the analyte, which is possible to calibrate by reference measurement procedure and reference material, the mean value after the traceability was confirmed can be used as the target value.

Oral administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in patients with osteoporosis in Japan. We conducted a prospective study to confirm the effects of 1 alpha(OH)D3 (Alfacalcidol, Alfarol Chugai Tokyo) on bone and calcium metabolism in elderly women with osteoporosis. Enrolled in the present study were 16 elderly osteoporosis women aged 72.6 +/- 4.5 years to whom 1 microgram of 1 alpha(OH)D3 was administered daily. Fasting blood and urine were obtained at baseline, 1 week, 4 weeks, 12 weeks and 24 weeks after the treatment. Monitored parameters were vitamin D metabolites, intact-PTH, bone alkaline phosphatase (BAP), osteocalcin (OC), deoxypyridinoline (DPD) and pyridiuium crosslinked type I collagen telopeptides (CTx). Serum 1 alpha, 25(OH)2D and PTH levels were significantly increased (p < 0.01) and decreased (p < 0.05), respectively at 1 week after commencing administration. There was a significant decrease of DPD (p < 0.05) at 12 weeks after commencing administration compared to the baseline levels. Serum levels of BAP and OC were found elevated at 1 week, and decreased at 12 weeks. In conclusion, the present study clinically confirmed that 1 alpha(OH)D3 stimulates bone formation in vitro. Long-term administration of 1 alpha(OH)D3 indirectly suppressed bone resorption through the suppression of parathyroid function in the elderly.

Although the basic concept for quality control of enzyme immunoassay (EIA) is the same as that of quality control of the usual chemical analysis, immunological analytic methods including enzyme immunoassay have some specific features depending on the method as compared with the chemical method. In addition to the usual QC method, therefore, it is necessary to add some QC techniques to control the variables derived from the method. In accuracy control of EIA, standard materials, reagents and analytical equipment will be the major sources of error. Points to be considered in accuracy control are described. In precision control of EIA, between-run precision is generally larger than within-run precision. In consideration of the characteristics, mean-Rs-R control chart method and Z-V control chart method appropriate for immunological method are described. Analytical sensitivity expressed as detectability and detection limits is very important in EIA. A procedure to determine the detection limits is described in detail. Between reagent lot difference in immunological reagent is considerably larger than that of chemistry reagent and a shift of the point on the control chart is not adequate to assess the reliability of the patient data. Therefore, an evaluation method of the between reagent lot difference is described. General procedures of precision control are not described here because the procedures are well known.

Quality control in clinical laboratory has a longer than forty-year history after its introduction. At present, quality control has been considered as one of essential tools to evaluate the quality of clinical laboratory data. However, several problems to be solved have still remained. I clarify the problems at present and declare the themes in future. Problems of internal quality control (IQC): Analytical precision of clinical laboratory test has remarkably improved recent years because of the advancement of technologies including analytical procedures and instruments. However, analytical accuracy has not attained the subjects. Furthermore, QC procedures have been converting into subjects and it has been generally considered that using a lot of QC material and QC method is a good manner. As a result, fundamental control procedures such as material control, reagent control and instrument maintenance have been ignored. Problems of external quality control (EQC): It has been considered that EQC serves as an indicator of analytical accuracy and shows the average analytical performance of all participants. However, some problems have remained as follows: (1) Problem of samples for proficiency testing. (2) Problem of classification of peer group. (3) Problem of target value. (4) Problem of evaluation criteria. In general, various IQC methods have been used without careful consideration. However, I would like to emphasize that we have to select the best QC method which can detect the error to be checked according to the method performance. For this reason, we have to grasp the purpose of QC and be careful to not change the subjects into the QC procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

It has been well known that the determination of CK-MB is a useful parameter for the diagnosis of acute myocardial infarction (AMI). Currently, several methods such as Electrophoresis, Ion-exchange chromatography, Immunoinhibition method and Protein mass determination are available. From a point of the diagnosis of AMI, the method should be satisfied with the requirements of high speed, ease to perform, high analytical specificity and high analytical sensitivity. However, there are no appropriate methods which can satisfy all of the requirement. In this paper, we have introduced the present situation concerning the determination of CK-MB in our hospital and discussed the results of study on the IMx method based on the determination of protein mass of CK-MB. We obtained good results in the fundamental study and found some advantages of protein mass determination. The first advantage was its high analytical specificity by use of monoclonal antibody. The second advantage was its high analytical sensitivity because of its low detection limit. The third advantage was the stability of sample because the antigenicity of CK-MB to the antibody of reagent is stable comparing with that of enzyme activity. From those advantages, the mass determination of CK-MB will be a useful method for the diagnosis of AMI in the near future.

We have reviewed the current methods of determining serum and urine myoglobin. Qualitative determination of urine myoglobin has been possible for over 20 years, but the quantitative determination is a recent development. Between 1963 (spectrophotometry) and 1978 (radioimmunoassay, RIA), efforts have been made to develop a more sensitive determination method. The RIA method thus developed has a sensitivity as high as 1 ng/ml. Such methods are valuable in the diagnosis of acute myocardial infarction. Recently, simple, rapid, and non-isotopic method such as enzyme immunoassay (EIA) and latex agglutination test have been developed and made rapid determination possible. We applied the "Mb-latex [Seiken]", one such latex agglutination method to the TBA-30 R single-multi type automated analyzer. We obtained good results in the fundamental study such as in precision and accuracy. The reference ranges obtained using serum and urine samples corresponded to the values reported by others with the exception of the lower limit of the ranges. Proficiency testing data using the same reagents and same samples at five laboratories revealed some systematic biases. The reasons for such interlaboratory differences is not clear. However, these systematic biases may be due to the type of equipment, the type of calibration procedure and others including reagents and standard solutions. We are continuing our effort to improve the reliability of interlaboratory data.

From January 1985 to June 1988, the authors have treated 138 cases of head and neck cancers. Among this number, six cases (4.3%) involved patients with a multiple primary cancer. With the exception of 1 case, all patients were male with a history of heavy smoking and excessive drinking. The primary cancer of the head and neck was most frequently located in the hypopharynx, and a secondary multiple cancer in the upper digestive tract especially the esophagus. Although we were unable to detect an early esophageal cancer by an esophagogram in some cases, each lesion could be detected by using lugol stain and gastrointestinal endoscopy.

We report a clinicopathological study on 100 japanese patients with peritoneal mesothelioma encountered between 1911 and 1982. Fifty-six were males and 44 were females, they ranged in age from 10 months to 83 years. As the inducement materials, asbestos was reported in 5 and thorium in 2 patients. Clinical symptoms were abdominal distension in 56 and abdominal pain in 50 patients. Thrombocytosis and hypoglycemia were observed in 7 and 3 patients, respectively. Macroscopically, the peritoneal mesothelioma was localized in 7, diffuse in 86 and not described in 7 patients. The pathological classification was benign in 5 and malignant in 77 cases. According to Stout's classification, the peritoneal mesothelioma was tubular in 43 mixed in 25 and fibrous type in 11 cases. Based on our findings we suggest that peritoneal mesotheliomas are on the increase in Japan.

We reported an operated patient with localized peritoneal mesothelioma. The patient was a 39-year-old man who had occasionally complained of left hypochondralgia for 5 years before admission. Progressive anemia due to hemorrhage into the peritoneal cavity was noted after admission. Peritoneoscopy revealed the bleeding to be located between the left lobe of the liver and the anterior wall of the stomach. On the 22nd hospital day, surgery was performed and a fist-sized tumor was resected. Microscopically, it was fibrous malignant type of the peritoneal mesothelioma. Chemotherapy was performed 3 times after the operation, and the patient is living and well 1 year and 8 months postoperatively.

One hundred and ninety seven patients with upper gastrointestinal bleeding were each administered and endoscopic local injection of hypertonic saline epinephrine (HS-E) solution at our hospital over a 5-year period, from the Spring of 1981 to March of 1986. Peptic ulcers were found in 162 of the patient. Vessels could be visibly detected in the 148 (91.4%)-A group, but not in the 14 (8.6%)-B group. A comparison of the number of endoscopic local injections to each of these groups indicated no significant differences in types of bleeding, systemic complications, or sites of bleeding. The excellent hemostatic effect of HS-E is due to the fact that local injection of its solution can be repeated in large quantities for various types of bleeding.