Comparison of the Japan Society of Clinical Chemistry reference method and CDC method for HDL and LDL cholesterol measurements using fresh sera.

OBJECTIVES: In 2009, the Japan Society of Clinical Chemistry (JSCC) recommended a reference method for the measurement of serum high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels. This automated method uses cholesterol esterase-cholesterol dehydrogenase to measure cholesterol levels in fractions obtained after ultracentrifugation and dextran sulfate/magnesium chloride precipitation. In the present study, using fresh samples, we compared the LDL-C and HDL-C levels measured using this method with those measured using the traditional Centers for Disease Control and Prevention (CDC)-beta-quantification (BQ) method. DESIGN: and methods: Using both the JSCC and CDC-BQ methods, LDL-C/HDL-C levels were measured in 47 non-diseased and 126 diseased subjects, whose triglyceride levels were lower than 11.29 â€‹mmol/L (1000 â€‹mg/dL). RESULTS: For LDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.991x + 0.009 â€‹mmol/L; r â€‹= â€‹0.999; and Sy/x â€‹= â€‹0.025 â€‹mmol/L, where x is the mean LDL-C level measured using the CDC-BQ method. Similarly, for HDL-C, the equation of the line representing the correlation between the two methods was y â€‹= â€‹0.988x + 0.041 â€‹mmol/L, r â€‹= â€‹0.999, and Sy/x â€‹= â€‹0.019 â€‹mmol/L, where x is the mean HDL-C level measured using the CDC-BQ method. CONCLUSIONS: The JSCC method agreed with the CDC-BQ method in cases of both non-diseased and diseased subjects, including those with dyslipidemia.

S-1-containing chemotherapy for patients with non-small-cell lung cancer: A population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.

To evaluate the efficacy and safety of S-1 monotherapy, S-1-containing combined chemotherapy and S-1 containing chemoradiotherapy for non-small cell lung cancer (NSCLC), a population-based observational study was performed. The efficacy and safety of the chemotherapies were evaluated at 13 institutes in a prefecture of Japan between April 2011 and March 2015. Datasets were obtained from 282 patients with NSCLC. For either wild-type or mutated epidermal growth factor receptor (EGFR), these three therapy groups generated almost identical response results and toxicity profiles as those in previously reported clinical trials, although the present study appeared to have slightly lower survival rates compared with those in the previous clinical trials. This may be due to the inclusion of patients in poor condition, and S-1 therapy being administered in the second, or later, line of therapy. In conclusion, the present study has confirmed that S-1-containing chemotherapy is effective against wild- and mutated-type EGFR NSCLC, and it is also tolerable in clinical practice.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer.

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41-57 days) and 5.3 months (134-181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44-80 days] compared with the younger group (median, 46 days; 95% CI: 35-53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142-239 days vs. median, 146 days; 95% CI: 114-185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.

Bevacizumab-containing chemotherapy for non-small cell lung cancer patients: a population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.

To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC patients were evaluated at 14 sites (17 hospital departments) in a prefecture of Japan between December 2009 and August 2011. Complete data sets were obtained from 159 patients with NSCLC. The median age was 66 years, and 34.0 % of the patients were 70 years or older. The overall response rate to bevacizumab therapy was 41.6 %, and the disease control rate was 78.5 %. In 88 patients who received bevacizumab-containing chemotherapy as first-line therapy, the response and disease control rates were 55.0 and 78.9 %, respectively. The incidence of clinically significant (grade 3 or more) adverse events was generally low: proteinuria occurred in 2 (1.3 %) patients, hypertension in 2 (1.3 %), hemoptysis in 1 (0.6 %), and interstitial pneumonia in 1 (0.6 %). The time to treatment failure (TTF) in the 159 patients was 169 days, and the median overall survival (OS) was 580 days. In patients who received bevacizumab-containing chemotherapy as first-line therapy, the TTF and OS were 152 and 520 days, respectively. The difference in TTF between patients who received bevacizumab-containing chemotherapy as first-line therapy and those who received it as second-line or later-line therapy was not significant (p = 0.4971). With regard to first-line therapy, the difference in TTF between patients treated with carboplatin + pemetrexed + bevacizumab and those treated with carboplatin + paclitaxel + bevacizumab was not significant (p = 0.9435). We deduced that bevacizumab-containing chemotherapy is effective against NSCLC and also tolerable in clinical practice.

A population-based study of gefitinib in patients with postoperative recurrent non-small cell lung cancer.

There is no standard treatment and there are no clearly defined guidelines for the treatment of postoperative recurrent non-small-cell lung cancer (NSCLC). We performed a retrospective population-based study to assess the benefits of treatment with gefitinib in patients with a postoperative recurrence of NSCLC in general clinical practice. This retrospective population-based study was conducted on patients with postoperative recurrent NSCLC who had been treated with gefitinib at 14 institutions in Ibaraki Prefecture between July 2002 and September 2007. The objective response rate to gefitinib therapy was 37.6% for local and distant recurrence. The median survival time following the start of gefitinib therapy was 12 months, and the one-year and two-year survival rates were 48.9 and 28.9%, respectively. The median survival time of the females was 19 months, and the median survival time of the males was 9 months (p=0.002). Univariate analysis showed that female gender, adenocarcinoma, a performance status (PS) of 0-1 and absence of smoking history were favorable prognostic factors. Only female gender and a PS of 0-1 were independent statistically significant prognostic factors in the multivariate analysis. The rate of greater than grade 1 interstitial lung damage as an adverse event was 3.5%. Gefitinib is a feasible treatment for postoperative recurrent NSCLC in general clinical practice, and a good response and prolonged survival were obtained, similar to the findings reported in published clinical studies that were conducted on highly selected patients.

A case of diffuse alveolar hemorrhage associated with tegafur plus uracil and warfarin therapy.

A 72-year-old man who received warfarin for myocardial infarction (prothrombin time-international normalized ratio [PT-INR] controlled between 2.2 and 2.5) for 2 years. He developed lung cancer, underwent surgery, and received tegafur plus uracil (UFT) after 1 month. After 2 months, he was admitted for hemoptysis and dyspnea. Chest radiography and computed tomography showed bilateral alveolar infiltration (PT-INR, 8.9). Bronchoalveolar lavage fluid (BALF) disclosed hemorrhagic features in sequential samples. And he was diagnosed with diffuse alveolar hemorrhage (DAH). A known interaction exists between fluoropyrimidines and warfarin. So, they were discontinued, and vitamin K was intravenously administered. One day later, the PT-INR returned to 1.14. The symptoms improved and, alveolar infiltration resolved after 2 weeks. Alveolar hemorrhage may be due to an interaction between UFT and warfarin. When fluoropyrimidines and warfarin are prescribed simultaneously, we recommend that PT-INR should be closely monitored.

[A case of MPO-ANCA positive vasculitis associated with multiple pulmonary nodules following propylthiouracil treatment].

A 34-year-old woman who had been treated with propylthiouracil (PTU) for hyperthyroidism, was admitted because of bloody sputum and pyrexia. The chest CT scan showed some nodules in both lung fields. The serum level of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was high, but proteinase-3 antineutrophil cytoplasmic antibody (PR-3 ANCA) was negative. A limited form of Wegener's granulomatosis without PR-3 ANCA was ruled out, because of the absence of abnormalities in the upper airway and kidney. No lesions other than the multiple pulmonary nodules of the lung were detected. We diagnosed MPO-ANCA associated vasculitis induced by PTU. After the termination of PTU, bloody sputum, pyrexia, and pulmonary nodules improved spontaneously and the serum level of MPO-ANCA returned to normal gradually. The case of MPO-ANCA positive vasculitis associated with multiple pulmonary nodules following propylthiouracil treatment is very rare.

[A case of lung cancer mimicking rupture of a thoracic aortic aneurysm].

A 56-year-old man visited another hospital complaining of hemoptysis. A chest radiograph showed expansion of the left upper mediastinum which seemed to be a mass-like lesion. He was referred to our hospital for further investigations. Before further examination, however, he presented to the emergency room with sudden onset of severe back pain. Rupture of a thoracic aortic aneurysm was suspected because of the clinical symptoms and the findings of emergency enhanced CT scanning. Emergency surgery was performed at the other hospital, and frozen section results indicated that the lesion was a non-small cell lung cancer. The pathology report of the surgical specimens revealed poorly differentiated adenocarcinoma of the lung with infiltration of the aortic wall. Postoperative chemotherapy was added, and the patient is doing well 10 months after operation. Some cases of tumor mimicking aortic aneurysm have been reported. We reported this case of lung cancer mimicking the rupture of a thoracic aortic aneurysm.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.

Modeling biochemical pathways using an artificial chemistry.

Artificial chemistries are candidates for methodologies that model and design biochemical systems. If artificial chemistries can deal with such systems in beneficial ways, they may facilitate activities in the new area of biomolecular engineering. In order to explore such possibilities, we illustrate four models of biochemical pathways described in our artificial chemistry based on string pattern matching and recombination. The modeled pathways are the replication of DNA, transcription from DNA to mRNA, translation from mRNA to protein, and the oxidation of fatty acids. The descriptions show that the present approach has good modularity and scalability that will be useful for modeling a huge network of pathways. Moreover, we give a procedure to perform reasoning in the artificial chemistry, which checks whether a specified collection of molecules can be generated in a given model, and we demonstrate that it works on a model that describes a natural biochemical pathway.

Modeling molecular computing systems by an artificial chemistry - its expressive power and application.

Artificial chemistries are mainly used to construct virtual systems that are expected to show behavior similar to living systems. In this study, we explore possibilities of applying an artificial chemistry to modeling natural biochemical systems-or, to be specific, molecular computing systems-and show that it may be a useful modeling tool for molecular computation. We previously proposed an artificial chemistry based on string pattern matching and recombination. This article first demonstrates that this artificial chemistry is computationally universal if it has only rules that have one reactant or two reactants. We think this is a good property of an artificial chemistry that models molecular computing, because natural elementary chemical reactions, on which molecular computing is based, are mostly unimolecular or bimolecular. Then we give two illustrative example models for DNA computing in our artificial chemistry: one is for the type of computation called the Adleman-Lipton paradigm, and the other is for a DNA implementation of a finite automaton. Through the construction of these models we observe preferred properties of the artificial chemistry for modeling molecular computing, such as having no spatial structure and being flexible in choosing levels of abstraction.

Percutaneous CT-guided radiofrequency ablation of pulmonary malignant tumors: preliminary report.

OBJECTIVE: Radiofrequency ablation (RFA) is frequently used for hepatic malignant tumors, but few reports discuss its use for lung tumors. We report our pilot clinical study with RFA for the treatment of pulmonary malignant tumors. PATIENTS AND METHODS: Five patients with histologically-proven malignant primary and three metastatic lung tumors underwent a total of 11 RFA procedures. RFA was performed in two patients as palliative therapy to shrink the tumors and in six as radical therapy. All RFA was performed by the percutaneous CT-guided approach. RESULTS: Three tumors were completely ablated by one procedure. Contrast CT revealed cyst cavity formation or scar formation at these three tumors. Gd contrast-enhanced MRI revealed cystic lesions with ringlike enhancement or scar formation. Partial ablation after the first procedure was noted in six tumors including the two palliative cases. RF ablation was well tolerated in all patients. Intraprocedural complications included six cases of pneumothorax (one patient required chest tube placement), six cases of pleural effusion (two patients required chest tube placement), one case of pneumonia (improved immediately with antibiotics), three cases of bloody sputum (mild), and six cases of chest pain (all cases after the procedure). CONCLUSIONS: This pilot clinical study demonstrates that CT-guided RFA is a relatively safe and effective treatment option for malignant lung tumors. Additional trials are needed to determine the safety, efficacy, and optimal indications of RFA.

Effects of acute exercise on lung antioxidant enzymes in young and old rats.

The lung could be the target organ to cellular damage, since it is directly exposed to high concentrations of oxygen. Acute exercise and age would be an added challenge to the lung, and therefore, we investigated alterations of major lung antioxidant enzymes (manganese-superoxide dismutase, Mn-SOD; copper-zinc-SOD, Cu-Zn-SOD; glutathione peroxidase, GPX; catalase, CAT) activities and mRNA expressions in young (4 months old) and old (26 months old) male Wistar rats with exercise. Thioredoxin reductase (TrxR) activity was also investigated. Mn-SOD and Cu-Zn-SOD increased with age, but age did not affect GPX, CAT, or TrxR activity. Acute exercise in young animals increased the activities of Mn-SOD, Cu-Zn-SOD, and CAT. In contrast, only Mn-SOD increased significantly in the old animals. The mRNA expressions of Mn-SOD, Cu-Zn-SOD and GPX were not altered with age, while CAT mRNA expression decreased with age. Acute exercise had no significant effect on any of the antioxidant enzyme mRNA expression. Moreover, reactive carbonyl derivative increased with age, but no significant changes were detected after acute exercise in either group. In summary, antioxidant enzymes responsible for the removal of hydrogen peroxide were unable to increase their enzyme activities in the old animals with exercise.

Proposal of automation of candidate reference method for the accurate serum cholesterol assay in clinical laboratories.

BACKGROUND: In 2001, Japan Society of Clinical Chemistry (JSCC) recommended the cholesterol dehydrogenase (CD)-UV method as a comparative method for serum cholesterol measurement in Japan. Although the CD-UV method is intended to standardize routine laboratory tests, it requires complex manipulations, and has been difficult to use for the evaluation of clinical laboratories. We therefore attempted to automate this method using reagents specified by JSCC and developed a simple automated method. METHODS: We evaluated the simple automated method using 2 general instruments (JCA-BM12 and H-7170S). The linearity was confirmed for the range over 15.52 mmol/l. The coefficients of variation for 20 measurements of serum containing 2.5 and 6.1 mmol/l of cholesterol were < 1.0%, respectively. No interference by bilirubin, ditauro bilirubin, hemoglobin and chylomicrons was observed in this method. When measurement data with JCA-BM12 were compared with those using the comparative method, the correlation coefficient was 0.999 (n=23), the regression formula was y=0.992x - 0.0036 (mmol/l), and the bias was 0.8%. A similar data was obtained with H-7170S. Thus, in both comparisons, the bias was within the target (+/- 3.0%). CONCLUSIONS: This automated method provides a valid means of implementing the serum cholesterol measuring method recommended by JSCC.

[A case of pseudo-meigs syndrome due to ovarian clear cell adenocarcinoma].

A 59-year-old woman was admitted with dyspnea. A chest X-ray film revealed a large amount of pleural effusion at the both sides. No malignant cells were found in bilateral pleural effusions. Computed tomography (CT) of the abdomen showed a huge mass of the right ovary with a small amount of ascites, suggesting a diagnosis of Meigs syndrome. The ovarian mass and the neighboring organs, including the uterus and the greater omentum, were surgically removed, and then both the bilateral pleural effusion and ascites disappeared after the surgery. The histopathological examination revealed that the mass was clear cell adenocarcinoma of the ovary (stage IIc), indicating that the disease was pseudo-Meigs Syndrome. This is the second report of pseudo-Meigs Syndrome caused by clear cell adenocarcinoma of the ovary in Japan.

Subacute cor pulmonale due to tumor embolism.

We describe a patient wih subacute cor pulmonale caused by tumor emboli in the lungs. A 64-year-old female suffering from a subacute progressive cough and shortness of breathing died of severe pulmonary hypertension seven days after admission. Neither chest CT scans nor lung perfusion scintigraphy showed any abnormal findings. Microscopic examination after an autopsy revealed diffuse intravascular tumor emboli occluding not only the small pulmonary arteries and arterioles, but also the lymphatic vessels, which were suggested to be metastases of a breast carcinoma resected five years previously. Thus, pulmonary tumor embolism should be considered in the differential diagnosis of primary pulmonary hypertension, particularly in patients with a past history of cancers.

Primary seminoma in the middle mediastinum.

Primary mediastinal seminoma is a relatively rare tumor usually located in the anterior mediastinum. We report here an extremely rare case of a 66-year-old man with primary seminoma in the middle mediastinum. A physical examination showed lymphadenopathy in the right supraclavicular area. A chest CT confirmed the presence of a tumor occupying the retrotracheal space. A histological examination demonstrated metastatic seminoma from the open biopsy of the lymph node. Abdominal, pelvis, and cerebral CT scan and testicular ultrasound were negative. Thus, primary mediastinal seminoma in the middle mediastinum with supraclavicular lymph node metastasis was diagnosed.

A large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water--epidemiologic manifestations.

OBJECTIVE: To study the epidemiologic manifestations of a large outbreak of Legionnaires' disease due to an inadequate circulating and filtration system for bath water. PATIENTS: In June 2000 at Ishioka City, Ibaraki Prefecture, a large outbreak of Legionnaire's disease occurred, as a result of an inadequate circulating and filtration system for communal bath water. This outbreak was the worst ever experienced in Japan, involving a total of 34 patients (20 confirmed, 14 probable), 3 of whom died. MEASUREMENTS AND RESULTS: Legionella pneumophila serogroup 1 was isolated from sputum culture in two patients. Bacteriological culture of the public bath water subsequently yielded large numbers of Legionella species. Cleavage of genomic DNA showed that restriction fragment patterns coming from clinical and environmental isolates of L. pneumophila serogroup 1 were closely related, focusing the inquiry to a public bathhouse where a circulating filtration system was suspected as the source of infection. CONCLUSIONS: It was later concluded that the circulating filtration system adopted for bath water was marred by a serious design flaw that subsequently caused the mass outbreak. Specifically, a line of the bath water was being returned to the bath without undergoing heat exchange or sterilization by chlorine; and the Legionella species that had proliferated in the filter and the bright stone filtration unit were allowed to return to the bath, eventually culminating in a mass infection.