Variability in detection and quantification of interferon ß-1b-induced neutralizing antibodies.

BACKGROUND: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs. METHODS: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists. The myxovirus protein A (MxA) induction assay, the cytopathic effect (CPE) assay (two laboratories), or the luciferase assay were used. Intra- and inter-laboratory agreement between assays with respect to NAb detection and NAb titer quantification were evaluated. RESULTS: High agreement for NAb detection (kappa coefficient, 0.86) and for titer levels was observed for the intra-laboratory comparison in the laboratory using the MxA induction assay performed three years ago and now. A similarly high agreement for NAb detection (kappa coefficient, 0.87) and for titer quantification was noted for the MxA assay of this laboratory with one of two laboratories using the CPE assay. All other inter-laboratory comparisons showed kappa values between 0.57 and 0.68 and remarkable differences in individual titer levels. CONCLUSIONS: There are considerable differences in the detection and quantification of IFNB-induced NAbs among laboratories offering NAb testing for clinical practice using different assay methods. It is important that these differences are considered when interpreting NAb results for clinical decision-making and when developing general recommendations for potentially clinically meaningful NAb titer levels.

Retrospective investigation of the clinical effects of tazobactam/piperacillin and sulbactam/ampicillin on aspiration pneumonia caused by Klebsiella pneumoniae.

Klebsiella pneumoniae is an important causative bacterium of aspiration pneumonia in many elderly patients. We retrospectively investigated the clinical effects of the early treatment of aspiration pneumonia and background factors in 24 patients from whom Klebsiella pneumoniae was isolated. Sulbactam/ampicillin (SBT/ABPC) was selected for early treatment in 12 of the 24 patients diagnosed with aspiration pneumonia, and tazobactam/piperacillin (TAZ/PIPC) was selected for the other patients. The effective rates and success rates of early treatment were significantly higher in the TAZ/PIPC group than in the SBT/ABPC group (p = 0.003 and 0.027, respectively). Although no significant difference was noted because of the limited number of cases, the survival rates after 30 days were 91.7 and 58.3 % in the TAZ/PIPC and SBT/ABPC groups, respectively. Several bacteria isolated with Klebsiella pneumoniae were resistant bacteria, such as methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa, and no anaerobe or extended-spectrum ß-lactamase-producing Klebsiella pneumoniae was isolated. Thirteen and 11 of the 24 cases were classified as healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), respectively, with no case classified as community-acquired pneumonia (CAP). As population aging progresses, the frequency of aspiration pneumonia classified as HCAP will increase. To cover anaerobes, it is necessary to select antibacterial drugs, such as TAZ/PIPC, for early treatment in consideration of resistant gram-negative bacteria to improve the outcome, and not drugs with weak activity against these bacteria.

Main bronchial diverticula in the subcarinal region: their relation to airflow limitations.

BACKGROUND: To date, bronchial diverticula have generally been treated as a pathological condition associated with chronic obstructive pulmonary disease (COPD), although only a limited amount of published information is available on the relationship between bronchial diverticula as depicted by multidetector computed tomography (MDCT) and airflow limitations. PURPOSE: To evaluate the relationship between airflow limitations and main bronchial diverticula in the subcarinal region using spirometry and thin-section MDCT. MATERIAL AND METHODS: A total of 189 consecutive adult patients were retrospectively evaluated based on spirometry and thin-section MDCT of the chest. All examinations were performed at our institution between June and October 2008. The study group included 70 women and 119 men with a mean age of 65 years (range 19-86 years). The relationship between the FEV(1)% and bronchial diverticula in the subcarinal region was analyzed (Student's t-test). RESULTS: The indications for conducting the examinations were pulmonary diseases (82 patients), cardiovascular diseases (22), extrapulmonary malignancies (74), and other conditions (11). A total of 84/189 (44.4%) patients showed bronchial diverticula, and the FEV(1)% of 70/84 (83.3%) patients was above 70. The FEV(1)% of patients with lesions ranged from 26.0 to 97.8 (mean 76.8), whereas the range was 28.1-94.4 (mean 73.7) in those without lesions. There was no significant association between the FEV(1)% and the presence of subcarinal bronchial diverticula (P > 0.05). CONCLUSION: Our data demonstrate that thin-section chest CT commonly demonstrates main bronchial diverticula in the subcarinal region in patients without airflow limitations. We propose that the presence of a small number of tiny bronchial diverticula under the carina may not be a criterion for the diagnosis of COPD.

A new apparatus for measurement of capacitance change in soft materials.

We have developed an apparatus with LC resonance circuit to measure a fast capacitance change accompanied by freezing of a supercooled water droplet that was placed in a capacitor space formed by a set of a needle and a copper plate. A trace of the capacitance change obtained exhibits a first rapid increase, a gradual growth, and a final steady state. The experimental capacitance change is in good agreement with that of the capacitance calculated with the finite element method.

[A case of multiple sclerosing hemangiomas of both lungs].

A 16-year-old Chinese girl was found to have abnormalities on chest roentgenography at a school health checkup in 2004, and she visited our outpatient clinic for the first time on July 2. Based on the imaging, there were multiple nodules ranging in size up to 5cm in the longest dimension, with regularly shaped clear margins, in both lungs. We considered lung metastases of a malignant neoplasm as the most likely diagnosis and performed a systemic workup but failed to make a clinical diagnosis. We therefore performed an open lung biopsy on November 8. Microscopically, the tumors consisted of a mixture of areas with a papillary pattern, a solid pattern and a sclerosing pattern. Component tumor cells were of two types: epithelial-like cells that covered the surface of the papillary structures and round or polygonal cells that showed a solid pattern of growth underneath. Immunohistochemical examinations revealed that these tumor cells were positive for an alveolar epithelium marker. From these results, we made a diagnosis of sclerosing hemangioma. Here we report a rare case of multiple sclerosing hemangiomas together with a review of the literature.

[A case of acute exacerbation of chronic pulmonary thromboembolism with essential thrombocythemia during treatment for hemoptysis].

An 89-year-old woman with essential thrombocythemia and chronic respiratory failure was admitted for treatment of hemoptysis. She stopped taking aspirin and was given tranexamic acid. Though her hemoptysis improved, respiratory failure suddenly worsened. As a result of various examinations and laboratory findings, acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though there was the risk of recurrence of hemoptysis, she started taking aspirin again. Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and hemorrhage are common complications of essential thrombocythemia, however, pulmonary thromboembolism is a rare complication. There is a possibility that the exacerbation of this case was caused by tranexamic acid as well as rest and cessation of aspirin. If a patient with essential thrombocythemia bleeds, we should be careful when using tranexamic acid.

[Clinical and virological studies of nosocomial conjunctivitis infection caused by adenovirus type 37 variant].

PURPOSE: To study the clinical features and virological analysis of the nosocomial adenoviral conjunctivitis cases occurring in the ophthalmology ward of Fukushima Medical University Hospital. MATERIALS AND METHODS: We studied the symptoms and clinical course of 61 patients who had adenoviral conjunctivitis caused by nosocomial infections in our hospital. We attempted to detect the adenovirus antigen, analyze the viral DNA, and isolate the virus from conjunctival swabs. RESULTS: The clinical symptoms of adenoviral conjunctivitis were mainly conjunctival hyperemia, discharge and conjunctival follicles. Adenoviral conjunctivitis patients who had undergone ophthalmic surgery had conjunctivitis in the operated eye. The sensitivity of Adeno-check was 78.9% in the in-patients. Adenovirus type 37 variant was detected by molecular analysis and viral isolation. CONCLUSIONS: Adenoviral conjunctivitis can often lead to outbreaks of nosocomial infection in the ophthalmic ward and sometimes requires makes necessary restriction of hospitalization and closing of the ward. Therefore, patients need to be observed carefully. The virological analysis of specimens from conjunctival swabs detected pathogens and provided useful information concerning adenoviral conjunctivitis.

[A case of advanced gastric cancer with lymphangitis carcinomatosa of the lung, successfully treated with paclitaxel and TS-1].

A 65-year-old man, who had been admitted to another hospital with complaints of severe cough and dyspnea, was transferred to our hospital for the further examination and therapy. The patient was diagnosed with advanced gastric cancer (type-3) with lymphangitis carcinomatosa of the lung. He was treated with combination therapy of 5-FU and cisplatin, and showed a complete response. However, because resistance was seen in the lymphangitis of the lung and the gastric lesion; and a liver metastasis was also seen, we attempted combination therapy with paclitaxel and TS-1. Sixty mg/m2/day of paclitaxel was administered intravenously on day 1 and 8, and TS-1 of 60-80 mg/m2/day was administered orally for 2 weeks followed by one drug-free week. After 2 courses of the combination therapy, the patient achieved a remarkable response in the lymphangitis carcinomatosa of the lung, but a slight response in the liver metastasis and gastric lesion.

[In vitro chemosensitivity test for hepatocellular carcinoma using collagen-gel droplet embedded cultures].

This study evaluated an in vitro assay for chemosensitivity test using a collagen-gel droplet-embedded culture drug sensitivity test (CD-DST) for hepatocellular carcinoma (HCC). In 25 patients with HCC, in vitro chemosensitivity to 5-fluorouracil (5-FU), epirubicin (EPI), and cisplatin (CDDP) was examined by CD-DST, and 5-FU, EPI, and paclitaxel (PTX) were examined in 38 patients with breast cancer. Successful rates of chemosensitive evaluation by CD-DST were 64% for HCC and 79% for breast cancers. Although chemosensitivities of breast cancer were 5-FU 23.1%, EPI 83.3%, and PTX 67.7%, only one HCC sample was sensitive to EPI. Growth rates of HCC for 7 days of culture were significantly lower than those of breast cancers (1.04 vs 3.61). The culture methods for HCC in CD-DST should be improved to estimate accurate results.

Evaluation of the chemosensitivity of primary cultured malignant melanoma cells using the collagen gel droplet-embedded culture drug sensitivity test.

Malignant melanoma usually shows resistance to a standard chemotherapy regimen. A useful in vitro method to evaluate individual chemosensitivity is required to select effective anti-cancer drugs. This study aimed to establish in vitro tumor response testing for malignant melanoma. We determined the chemosensitivity of primary cultured melanoma cells using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Nineteen tests were carried out for 15 cases of malignant melanoma. Primary cultured melanoma cells in collagen gel droplets were exposed to anti-cancer drugs, including cisplatin, adriamycin, dacarbazine, nimustine and vincristine. After a 7-day incubation in a serum-free medium, living melanoma cells in a collagen droplet were detected by image analysis after staining with Neutral red reagent. In vitro drug exposure conditions were determined to reproduce the value of the plasma area under the time-drug concentration curve in vivo. The rate of evaluation of the primary culture of melanoma cells was 78.9% (15/19 tests). The chemosensitivity of cisplatin, adriamycin, dacarbazine, nimustine and vincristine was 15, 62, 0, 0 and 62%, respectively. Dacarbazine was not suitable for CD-DST due to its prodrug characteristics. The CD-DST method was able to evaluate the chemosensitivity of malignant melanoma to anti-cancer drugs in vitro. This method can also be applied to estimate the efficacy of newly developed anti-cancer drugs in vitro.

Human rhinovirus 87 identified as human enterovirus 68 by VP4-based molecular diagnosis.

Human rhinoviruses (HRVs) are the major cause of respiratory infections. We developed a diagnostic method for HRVs based on the reverse-transcription polymerase chain reaction (RT-PCR) and VP4-based phylogenetic analysis. A set of primers used in the RT-PCR of human enteroviruses (EVs) appeared to be capable of amplifying all prototype strains of HRVs, each of which generated a 530-bp fragment. The single exception was HRV-87, which generated a 650-bp fragment, as observed in human EVs. The VP4 nucleotide sequence of HRV-87 showed more than 97% nucleotide identity with human EV-68, and formed a monophyletic cluster along with the prototype strain of EV-68 in the human EV-D cluster. HRV-87 showed the second highest homology (76.8%) with EV-70, another member of the human EV-D, in a sample of 66 human EVs and 12 HRVs. Therefore, HRV-87 should be reclassified into the cluster containing human EV-68.

Maintenance of serum immunoglobulin G antibodies to Epstein-Barr virus (EBV) nuclear antigen 2 in healthy individuals from different age groups in a Japanese population with a high childhood incidence of asymptomatic primary EBV infection.

Immunoglobulin G (IgG) antibodies to Epstein-Barr virus (EBV) nuclear antigens 2 and 1 (EBNA-2 and EBNA-1, respectively) were studied using sera from healthy individuals of a population with a high incidence of asymptomatic primary EBV infections during infancy or childhood in Japan. Two CHO-K1 cell lines expressing EBNA-2 and EBNA-1 were used for anticomplement and indirect immunofluorescence assays. The positivity rate for EBNA-2 IgG rose in the 1- to 2-year age group, increased and remained at a plateau ( approximately 45%) between 3 and 29 years of age (3- to 4-, 5- to 9-, 10- to 14-, and 15- to 29-year age groups), and then reached 98% by age 40 (>/== 40-year age group). Both seropositivity for EBNA-1 and seropositivity for EBNAs in Raji cells (EBNA/Raji) were detected in the 1- to 2-year age group, remained high, and finally reached 100% by age 40. The geometric mean titer (GMT) of EBNA-2 IgG reached a plateau in the 5- to 9- and 10- to 14-year-old groups and remained elevated in the older age groups (15 to 29 and >/== 40 years). The GMT of EBNA-1 IgGs increased to a plateau in the 1- to 2-year-old group and remained unchanged in the older age groups. The GMT of EBNA/Raji IgGs also reached a plateau in the 1- to 2-year-old group, remained level throughout the 3- to 14-year age groups, and decreased in the 15- to 29-year-olds. EBNA-2 IgGs emerged earlier than EBNA-1 IgGs in 8 of 10 patients with infectious mononucleosis, who were between 1 and 27 years old, and declined with time in three of eight cases. These results suggest that EBNA-2 IgG antibodies evoked in young children by asymptomatic primary EBV infections remain elevated throughout life, probably because of reactivation of latent and/or exogenous EBV superinfection.