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On-site winding of two helical coils of LHD started at the beginning of 1995, using a numerically controlled winding machine. They are large-scale pool-cooled superconducting coils which are designed to satisfy fully stabilized criterion. The conductor consists of Nb-Ti/Cu strands with a pure aluminium stabilizer and copper sheath. The main demanded values for winding the coils are 2.0 mm and 65 [[micro]meter] for the accuracy of coil and the average gap between layers, respectively. A winding method was established by trial of winding.

Purpose: The incidence and patterns of isolated brain failure was examined in patients with stage III non-small-cell lung cancer (NSCLC) treated with concurrent chemoradiation (CCRT).Materials and Methods: Between 1996 and 2003, a total of 68 patients with stage III NSCLC were treated with radical CCRT. Among them, 63 patients were evaluable. Radiation therapy with a mean total dose of 61.4 Gy and chemotherapy (typically platinum-based) were administered concurrently.Results: Other than locoregional failure, isolated brain failure was the most common failure pattern as the initial failure, occurring 2-37 months (median 6.5 months) after radical CCRT. The isolated brain failure rates as the initial failure at 1, 3, and 4 years were 9%, 13%, and 25%, respectively. Isolated brain failure as the initial failure occurred more frequently in T4 cases (39% at 4 years) compared to T1-3 cases (14% at 4 years) in our series (P = 0.0099).Conclusion: Except for locoregional failure, isolated brain failure was the most common initial failure pattern of stage III NSCLCs treated with radical CCRT. Isolated brain failure as the initial failure occurred even after 3 years. Isolated brain failure as the initial failure occurred more frequently in T4 cases than in T1-3 cases. [ABSTRACT FROM AUTHOR]

Introduction: The retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment., Methods: A retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses., Results: Gelatin hydrolysate at 5 % concentration effectively mitigated cell reflux in vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE., Conclusion: Gelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation., Competing Interests: The authors declare no conflict of interest., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Competing Interests: None.

Reactive oxygen species and nitric oxide (NO•) concomitantly play essential roles in guard cell signaling. Studies using catalase mutants have revealed that the inducible and constitutive elevations of intracellular hydrogen peroxide (H 2 O 2 ) have different roles: only the inducible H 2 O 2 production transduces the abscisic acid (ABA) signal leading stomatal closure. However, the involvement of inducible or constitutive NO• productions, if exists, in this process remains unknown. We studied H 2 O 2 and NO• mobilization in guard cells of catalase mutants. Constitutive H 2 O 2 level was higher in the mutants than that in wild type, but constitutive NO• level was not different among lines. Induced NO• and H 2 O 2 levels elicited by ABA showed a high correlation with each other in all lines. Furthermore, NO• levels increased by exogenous H 2 O 2 also showed a high correlation with stomatal aperture size. Our results demonstrate that ABA-induced intracellular H 2 O 2 accumulation triggers NO• production leading stomatal closure., Abbreviations: ABA: abscisic acid; CAT: catalase; cGMP: cyclic guanosine monophosphate; DAF-2DA: 4,5-diaminofluorescein-2 diacetate; H 2 DCF-DA: 2',7'-dichlorodihydrofluorescein diacetate; MeJA: methyljasmonate; NOS: nitric oxide synthetase; NR: nitrate reductase; POX: peroxidase; ROS: reactive oxygen species; SNAP: S -nitroso- N -acetyl-DL-penicillamine; SNP: sodium nitroprusside; NOX: NADP(H) oxidase.

Impact Statement: Cartilage particles derived from human induced pluripotent stem cells (hiPS-Carts) are one candidate source for transplants for treatment of articular cartilage damage. This study shows that hiPS-Carts integrate with each other in an in vitro model and analyzed the course of the integration. The integration starts at the perichondrium-like membrane at around 1 week and then progresses to the central cartilage within 4-8 weeks. The results indicate that FGF18 secreted from the perichondrium-like membrane accelerates the initial step of integration. The findings contribute to understanding how hiPS-Carts form repair tissue and provide clue to accelerate healing after transplantation.

The effects of the peroxisome proliferator, dehydroepiandrosterone sulfate (DHEAS), and the typical cytochrome P450 (CYP) inducers phenobarbital (PB) and 3-methylcholanthrene (3-MC) on fatty liver were examined in rats. Treating rats with orotic acid caused marked accumulation of lipid droplets in the liver. This effect of orotic acid was almost eradicated by co-treatment with DHEAS and PB. While DHEAS or PB alone also alleviated fatty liver, treatment with 3-MC caused little effect on a reduction in lipid droplets. Histopathological examinations revealed numerous peroxisomes in the liver of rats treated with DHEAS. In addition, a significant increase in the expression on hepatic CYPs was observed in rats the fatty liver of which was attenuated. Regarding other enzymes associated with hepatic fatty acid oxidation, the expression levels of sirtuin 1, sirtuin 6, and carnitine palmitoyltransferase 1 were also upregulated most markedly by treatment with DHEAS alone. Thus, the attenuation in fatty liver observed in the present study is likely due to peroxisome proliferation and the induction of fatty acid-metabolizing enzymes by DHEAS and typical CYP inducers.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan., Methods:  Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS., Results: A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis., Conclusions: SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.

Subclinical hypothyroidism (SCH) has been associated with type 2 diabetes mellitus. However, it is unknown whether common complications of type 2 diabetes, such as diabetic nephropathy, are also present with SCH. Here, we investigated the association between SCH and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. In this multicenter cross-sectional study, we recruited 414 such patients who had no previous history of thyroid disease. Serum thyroid hormone levels and the urinary albumin:creatinine ratio were measured. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.0 mIU/L), and diabetic nephropathy was defined as urinary albumin/creatinine ratio ≥300 mg/g. The prevalence of SCH was 8.7% (n = 36) among patients with type 2 diabetes mellitus. The SCH group had a higher prevalence of dyslipidemia (p = 0.008) and diabetic nephropathy (p = 0.014) than the euthyroid group. Multivariate analysis identified significant positive associations between diabetic nephropathy and SCH (odds ratio [OR], 3.51; 95% confidence interval [CI], 1.10-10.0; p = 0.034), hypertension (OR, 4.56; 95% CI, 1.69-14.7; p = 0.001), and smoking (OR, 3.02; 95% CI, 1.14-7.91; p = 0.026). SCH may be independently associated with diabetic nephropathy in Japanese patients with type 2 diabetes mellitus.

Objective: This study aimed to investigate the association between periodontal disease and peptic ulcers in a working population., Methods: Self-administered questionnaires were distributed to all employees of a large insurance company in Japan. The questionnaire asked about their health status and lifestyle habits. Peptic ulcer was defined as either stomach ulcer, duodenal ulcer, or both. For the evaluation of periodontal disease, three indices were used: (a) loss of five or more teeth, (b) having been told of having periodontitis, and (c) periodontal risk score., Results: Of the eligible 28 765 subjects analyzed, peptic ulcer was present in 397 (1.4%). The results of bivariate analyses showed that a significantly higher proportion of subjects with peptic ulcer reported that they lost five or more teeth (35.3 vs. 17.4%, p<0.001) or that they were told they had periodontitis (33.5 vs. 20.7%, p<0.001). Moreover, the periodontal risk score was higher for those with peptic ulcer than those without (mean 0.83 vs. 0.59, p<0.001). In multivariate logistic regression analyses, statistical associations were found between the presence of peptic ulcer and loss of five or more teeth (odds ratio (OR): 1.41, 95% confidence interval (CI): 1.13-1.76, p<0.01), having been told of having periodontitis (OR: 1.28, 95% CI: 1.03-1.59, p<0.05), and a 1-point increase in the periodontal risk score (OR: 1.17, 95% CI: 1.04-1.30, p<0.01), respectively., Conclusion: Modest but statistically significant associations were found between the self-reported measures of periodontal disease and peptic ulcers.

Purpose: In the present study, the nonclinical safety profile of tolvaptan was evaluated., Methods: A series of safety pharmacology and toxicology studies were performed in vitro and in mice, rats, dogs, rabbits and guinea pigs., Results: In safety pharmacological studies, tolvaptan had no adverse effects on the central nervous, somatic nervous, autonomic nervous, smooth muscle, respiratory and cardiovascular, or digestive systems. In general toxicity studies, a single dose of tolvaptan up to 2,000 mg/kg was not lethal in rats and dogs. Tolvaptan did not cause any target organ toxicity in rats after treatment for 26 weeks or in dogs after treatment for 52 weeks at oral doses of up to 1,000 mg/kg/day. The toxicities observed in the present studies were generally attributable to the exaggerated pharmacological action of tolvaptan. In reproductive and developmental toxicity studies in rats, fertility was not affected. Suppressed viability or growth observed in the prenatal and postnatal progeny occurred at the maternally toxic dose of 1,000 mg/kg/day. In rabbits, tolvaptan showed teratogenicity at 1,000 mg/kg/day, a dose that was maternally toxic causing abortion. Tolvaptan was not genotoxic or carcinogenic, and did not induce phototoxicity, antigenicity or immunotoxicity., Conclusion: Nonclinical toxicity that precludes the safe administration of tolvaptan to humans was not observed. However, appropriate cautions should be taken in women of childbearing potential.

In order to ensure a widespread distribution in the lung and to avoid the effect of anesthesia, bleomycin at a total dose of 4.5 or 6.0 mg/kg was administered in four divided doses (0.5 ml/kg/time) at intervals of 2 h to male rats via a catheter (tracheotomy tube) without anesthesia. In comparison to vehicle (saline) controls, bleomycin-treated rats showed a significant suppression of body weight gain that was observed transiently at 4.5 mg/kg and continuously (throughout the 3-week observation period) at 6.0 mg/kg. Histopathologically, interstitial pneumonitis, thickening of alveolar walls, thickening of pulmonary arterial walls, foamy cells in alveoli, and hemorrhage were observed in both 4.5 and 6 mg/kg groups, and also emphysema in the 6 mg/kg group. Both groups exhibited a significant decrease in the partial pressure of arterial oxygen (PaO(2)) and a significant increase in alveolar-arterial oxygen tension difference (AaDO(2)), and a significant increase in erythrocyte count was observed in the 6 mg/kg group. Furthermore, both treated groups showed a significant increase in the ratio of the right ventricular weight versus left ventricle plus septum weights. The significant increase in erythrocyte count might have been caused by diffusion disturbance and ventilation-perfusion imbalance due to the pulmonary damage. These findings suggest that the present experimental method will be useful for clarification of the pulmonary damage induced by bleomycin in rats.

As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

Purpose: To clarify the usefulness of measuring serum amyloid A (SAA) levels in patients with polymyalgia rheumatica (PMR), we compared this parameter to C-reactive protein (CRP)., Subjects and Methods: The study included 10 patients with PMR, who could be prospectively followed up from the start of prednisolone (PSL) treatment until the CRP level decreased to 1 mg/dl or less. When the CRP level decreased, the subjects were divided into the group in which the symptom persisted (n = 6) and those in which the symptom disappeared (n = 4)., Results: In the group in which the symptom persisted, both CRP and SAA levels were significantly higher. When the CRP level decreased, there was no significant difference in the CRP level between the two groups. However, the mean SAA level in the group in which the symptom persisted (137.8 micrograms/ml) was significantly higher than that in the group in which the symptom disappeared (21.8 micrograms/ml). On the initial consultation, there was a positive correlation between CRP and SAA (R = 0.77). The SAA level was more sensitive than the CRP level (y = 94.899 x -51.22). When the CRP level decreased, SAA was much more sensitive (y = 222.92 x +6.9121), suggesting the usefulness of SAA after the start of PSL treatment., Conclusion: SAA may be a useful parameter of PMR activity.

Twenty-eight patients with Japanese spotted fever were clinically investigated. The diagnosis was determined by confirming an increase of specific antibody. All patients were treated with minocycline, and all recovered, excluding one patient with a fulminant course. Fever and exanthema were observed in all patients, and an eschar was pointed out in 20 (71%) patients. The platelet count was 10 x 10(4)/microl or lower in 8 (28%) patients. The fibrin degradation product (FDP)-level was abnormally high, 10 microg/ml or more, in 16 (57%) patients. The creatine kinase (CK) value was high in 14 of 22 patients, suggesting the presence of myositis. The leukocyte count, FDP, C-reactive protein, and soluble interleukin 2 receptor (sIL2-R) levels were significantly higher in severe cases. In the group without concomitant steroid therapy, mean times of 54.7 h and 101.4 h were required to reduce the temperature to 38 degrees C and 37 degrees C or lower, respectively, after the initiation of tetracycline treatment. There were 6 severe cases: 1 with disseminated intravascular coagulation, 2 with multiorgan failure, 1 with acute respiratory distress syndrome, and 2 with meningoencephalitis. These severe cases formed a group that required 6 or more days to initiate therapy after the onset (P < 0.005 vs non-severe group), showing that delay in diagnosis and therapy is the major cause of aggravation. In the 2 patients complicated by multiorgan failure, the sIL2-R level, produced by activated lymphocytes, was 10,000 U/ml or higher, suggesting that an sIL2-R level of more than 10,000 U/ml can be used as a marker of poor prognosis. It may be better that moderate to severe cases are treated with minocycline plus short-term steroid therapy.

Objective: The aim of this study was to assess the utility of 201Tl SPECT in the differential diagnosis of intracranial tumors and to determine the relationship between 201Tl uptake and histological types., Methods: Thirty-eight patients (19 males and 19 females) with thirty-eight brain tumors were evaluated with 201Tl-SPECT. The early and delayed 201Tl uptake ratio was calculated, and the retention index (RI) was applied as follows; RI = delayed uptake ratio/early uptake ratio., Results: The RI of malignant tumors was higher (0.72 +/- 0.18) than that of benign tumors (0.50 +/- 0.16) and the difference was statistically significant (p = 0.00045). The difference between high-grade glioma (0.80 +/- 0.15) and metastatic tumors (0.64 +/- 0.19) was statistically significant (p = 0.039)., Conclusion: 201Tl-SPECT may add useful biochemical information and could differentiate malignant brain tumors from benign lesions, but the RI of metastatic tumors varied depending on the organs with the primary lesion and histological types.

We encountered a patient with polymyalgia rheumatica (PMR) who exhibited fever as the main symptom for a long period without muscular pain. As an etiological factor, the condition may have been associated with nonsteroidal anti-inflammatory drugs (NSAIDs). A 71-year-old man consulted our Department of Orthopedics for fever and lumbar pain, which initially developed in early September 2000. Administration of NSAIDs resulted in the disappearance of lumbar pain. However, fever persisted. The C-reactive protein (CRP) level was persistently high. Therefore, on October 5, 2000, the patient was referred to our department. At the outpatient clinic, a detailed examination was performed. However, the etiology could not be determined. Repeated administration of NSAIDs resulted in pyretolysis, and the dose of NSAIDs was decreased from January 31, 2001. Severe fever appeared again, and inflammatory reaction also exacerbated. On March 11, 2001, muscular pain involving the bilateral shoulders and forearms suddenly developed. For diagnostic treatment, administration of prednisolone (PSL) at 10 mg/day was started. Muscular pain rapidly disappeared. According to Bird's criteria, PMR was diagnosed. After the dose of PSL was decreased to 7.5 mg/day, the course is good. PMR should be considered as the etiology of idiopathic fever in elderly patients.

A 72-year-old man was admitted to the emergency ward in our hospital on July 20, 2001, because of consciousness disturbance, fever, generalized skin eruption, and severe general weakness beginning 7 days previously. Physical examination on admission revealed marked systemic cyanosis, erythema, and purpura. Laboratory findings indicated disseminated intravascular coagulation (DIC) and multiorgan failure (platelet count, 0.9 x 10(4)/micro l; fibrin degradation product, 110 micro g/ml; C-reactive protein, 22.6 mg/dl). Soluble interleukin 2-receptor (sIL-2R) was markedly increased to 14 710 U/ml. Blood gas analysis demonstrated severe metabolic acidosis. He was diagnosed with multiorgan failure due to DIC. Administration of heparin and sodium bicarbonate was started immediately, but respiratory failure was exacerbated and systemic spasm caused by encephalitis was noted. Although he was supported by an artificial ventilator, deterioration of metabolic acidosis occurred, and the blood pressure decreased to less than 60 mm Hg. He died 5.5 h after admission. The serological test showed no positive antibody titers against Orientia tsutsugamushi, Rickettsia japonica, or Rickettsia typhi. However, a specific DNA band derived from R. japonica was detected by the polymerase chain reaction (PCR) method using a primer from a blood clot. Therefore, he was definitively diagnosed as having Japanese spotted fever. The PCR method may be markedly useful for establishing a definitive diagnosis of Japanese spotted fever during the critical stage.

We encountered 3 cases of polymyalgia rheumatica (PMR), in which serum amyloid A (SAA) levels were correlated with clinical pictures after normalization of ESR and CRP levels. Therefore, it is suggested that SAA may be a useful index for evaluating the severity of intractable PMR. Case 1: The patient was a 75-year-old man. Although ESR and CRP levels were normalized after the administration of PSL (20 mg/day), myalgia persisted. When the dose of PSL was reduced, PMR recurred, which was relieved by administering 15 mg/day of PSL. However, myalgia recurred again when the dose of PSL was reduced thereafter. The elevated SAA level (33.0 micrograms/ml) was normalized by continuous administration of PSL without reducing the dose, resulting in the relief of myalgia. Case 2: The patient was a 65-year-old woman. The administration of PSL was initiated at a dose of 15 mg/day. Although myalgia was relieved, the symptom and elevated SAA levels persisted for approximately 3 months. Thereafter, PMR recurred, and SAA levels were markedly increased to 78.2 micrograms/ml. However, the symptom of PMR was eliminated by continuously administering PSL without reducing the dose. Although the dose of PSL was then reduced after the decrease in SAA levels, PMR did not recur. Case 3: The patient was an 88-year-old woman. Although the symptom of PMR was relieved by administering 15 mg/day of PSL, myalgia persisted. Since SAA levels were increased to 106 micrograms/ml, PSL was continuously administered without reducing the dose, resulting in the disappearance of the symptom and normalization of SAA levels approximately 3 months later. Although the dose of PSL was then reduced to 12.5 mg/day, PMR did not recur.

Hydrogen peroxide (H2O2)-induced deacetylation of non-fluorescent acetyl resorufin (1) to fluorescent resorufin (2) as a novel indicator reaction for fluorometric detection of glucose using only glucose oxidase (GOD) is described. When a 1:1:1 mixture of 1 (in CH3CN), glucose, and GOD (each in pH 7.4 phosphate buffer) was incubated at 25 degrees C under aerobic conditions, the resulting solution turned yellow to fluorescent pink due to 2. The formation of 2 was markedly retarded on incubation under anaerobic conditions. When a mixture of 1 and H2O2 was incubated under aerobic conditions, the formation of 2 was noted as in the case of the enzymatic reaction of 1. These results demonstrated that the observed color change is brought about through deacetylation of 1 to 2 induced by H2O2 generated in GOD-catalyzed oxidation of glucose. With regard to the fluorometric traces of the enzymatic reaction with 1 (0.2 mM), GOD (0.5 mg/ml), and glucose at 25 degrees C, fluorescence intensity exhibited a linear relationship against glucose concentration between 0.2 and 2.0 mm, with a correlation coefficient of 0.997. Neither ascorbic acid, uric acid, nor bilirubin significantly interfered with the transformation of 1 to 2 through GOD-catalyzed oxidation of glucose.

Resorufin (1) has been found to act as an electron acceptor in glucose oxidase (GOD)-catalyzed oxidation of glucose. When a 1: 1: 1 mixture of solutions of 1 (5.0 microM), glucose, and GOD (4.0 mg/ml) in phosphate buffer (pH 7.4, 0.1 M) was incubated at 36 degrees C under aerobic conditions and the reaction was followed by a measurement of changes in fluorescence intensity due to 1, only two types of fluorometric traces were observed: (1) when a glucose solution of less than 0.7 mM was subjected to the enzymatic reaction, no consumption of 1 was observed; (2) the reaction with glucose at more than 1.0 mM always consumed 1, affording a regression fluorometric curve, and yet the obtained fluorometric traces could be almost superimposed on one another with no dependence on the glucose concentration. The reasons for the observed phenomena are discussed.

Background: The nonspecific cross-reacting antigen-50/90 (NCA-50/90) is a glycoprotein antigen which shares some antigenic determinants with carcinoembryonic antigen (CEA). No definite clinical value has been established for the measurement of NCA-50/90 in cancer patients., Methods: We established and evaluated a chemiluminescent enzyme immunoassay (CLEIA) specific for NCA-50/90 using two monoclonal antibodies., Results: No significant reactivity with 4 purified related antigens including CEA was found in the NCA-50/90 CLEIA. Serum samples (n = 572) from patients with malignant (n = 326) as well as from healthy individuals (n = 246) were analyzed by the NCA-50/90 CLEIA and by the established ACCESS CEA assay. The average sensitivity of NCA-50/90 for malignant disease was 40.8%, compared to 45.4% of CEA. Relatively high positive rates of NCA-50/90 were observed in sera from patients with lung cancer (72.0%), hepatoma (62.5%), pancreatic cancer (47.6%), breast cancer (35.6%), and colorectal cancer (34.5%). About 15% of patients with malignant disease were positive only for NCA-50/90. The levels of NCA-50/90 and CEA in sera from patients with malignant disease correlated only poorly., Conclusions: The present study suggests that increases in blood levels of NCA-50/90 occur in a population of cancer patients which is different from those with elevated levels of CEA and that NCA-50/90 might be useful for NCA-50/90-positive, but CEA-negative patients.

We carried out clinical and bacteriological studies on clavulanic acid/amoxicillin and amoxicillin in pediatric sinusitis at 11 general practice settings. The results are summarized as follows. 1. The major isolated organisms from content of middle meatus were Streptococcus pneumoniae 32.2%, Haemophilus influenzae 32.0% and Moraxella subgenus Branhamella catarrhalis 25.1%. Similar results were observed for the major isolates from nasopharynx. 2. 62.1% of S. pneumoniae isolated were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. 3. Drug resistant S. pneumoniae was isolated from 38.6% of all cases. 4. Regarding MIC90, CVA/AMPC showed superior antimicrobial activity against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis. 5. The clinical efficacy, bacteriological efficacy and utility of CVA/AMPC-treated group were 78%, 58% and 72.8%, respectively, and they were significantly superior to AMPC-treated group. 6. Adverse reactions were observed in 11.2% of CVA/AMPC group, involving diarrhea and stool loose and there was no statistical deference from those of AMPC group.

We carried out clinical and bacteriological studies on clavulanic acid/amoxicillin and amoxicillin in pediatric acute otitis media at 14 general practice settings. The results are summarized as follows. 1. The major isolated organisms from content of middle ear effusion were Streptococcus pneumoniae 31.8%, Haemophilus influenzae 35.8% and Moraxella subgenus Branhamella catarrhalis 1.5%. Similar results were observed for the major isolates organisms from content of nasopharynx Streptococcus pneumoniae 31.1%, Haemophilus influenzae 33.9% and Moraxella subgenus Branhamella catarrhalis 19.2%. 2. 42.2% of S. pneumoniae isolated from middle ear effusion were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. 3. 46.7% of S. pneumoniae isolated from nasopharyngeal swab were drug resistant S. pneumoniae (PISP, PRSP) and they were increasing year by year. The incidence of drug resistant S. pneumoniae isolated from all cases and organisms were 26.3% and 14.5%, respectively. 4. On MIC90, antimicrobial activity of CVA/AMPC against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella subgenus Branhamella catarrhalis was superior to SBTPC. 5. In the evaluation of clinical efficacy, bacteriological efficacy and utility, CVA/AMPC-treated group was significantly superior to AMPC-treated group. 6. Adverse reactions were observed in 22% of CVA/AMPC-treated group, involving diarrhea and loose stool.