Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation.

A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium.

The views of doctors on registration trials in a Japanese rural area: a survey of medical institutions registered to the Tokushima Network for Clinical Trials.

Tokushima University Hospital has established the Tokushima Network for Clinical Trials (TNCT) to promote clinical trials in the area in collaboration with the Tokushima Medical Association. The present study investigated the views of doctors towards registration trials in the TNCT. A questionnaire was provided to 49 clinics/hospitals registered to the TNCT in 2006 and 38 (78%) responded. It revealed that 48% of doctors were aware of registration trials and 87% were favourable towards participating as investigators in them. They considered close contact with developmental drugs, advancement of therapy and the opportunity to learn about state-of-the-art treatment as benefits of participation. The main areas of difficulty included management of adverse reactions and patients' refusal to take part. Many doctors wanted more opportunity to learn about trial-related issues such as regulations. The survey indicates that the TNCT needs to develop the infrastructure and enlighten participants to promote registration trials in this rural regional area.

Immediate effects of a rucksack type orthosis on the elderly with decreased lumbar lordosis during standing and walking.

The spinal orthosis, the so-called rucksack type orthosis (RO), has been used to relieve low back pain and fatigue during prolonged standing and walking for the elderly with spinal deformities. However, little is known about the RO's kinematical effects. Twenty-three elderly (78.9 +/- 6.9 years old) participated in experiment 1, and 13 elderly (78.4 +/- 7.9 years old) in experiment 2. They had decreased lumbar lordosis or lumbar kyphosis. In experiment 1, using the "Spinal Mouse", which can measure spinal curvature, the effects of the RO on posture during standing were investigated. In experiment 2, using electromyography, the effects of the RO on muscle activity during standing and walking were clarified. Lumbar curvature and the trunk angle of inclination during standing improved significantly when the RO was used. Back extensor muscle activities (T9, L3, and L5) during standing and walking decreased significantly when the RO was used. There were no significant differences in the activities of the upper trapezius and vastus lateralis during standing and walking. The present study suggests that the elderly with lumbar deformities might be able to stand and walk more efficiently with the RO. The RO could prove to be valuable in preservation therapy for the elderly with decreased lumbar lordosis or lumbar kyphosis.

Serum sodium levels in patients with Kawasaki disease.

The purpose of this study was to assess the hypothesis that lower serum sodium levels are associated with cardiovascular sequelae in patients with Kawasaki disease (KD). We used the database of the 16th nationwide survey of KD in Japan. We investigated the distribution of serum sodium levels and the relationship between serum sodium levels and cardiovascular sequelae. Of the reported cases, serum sodium levels were reported in 13,569 patients (89%). The proportion of patients with serum sodium levels 130 mEq/L or less, was greater in complete cases than in incomplete cases. The proportion of patients with serum sodium levels 130 mEq/L or less was increased with age. The largest proportion of patients with serum sodium levels 130 mEq/L or less was found in the category of 3-5 days since onset of illness. A serum sodium of level 135 mEq/L or less was an independent risk factor for cardiovascular sequelae (odds ratio, 1.79, 95% confidence interval, 1.42-2.26). Among patients with KD, there are significant differences in serum sodium levels between diagnostic categories, age, and days since the onset of illness. The sodium level may be a simple predictor of cardiovascular sequelae.

Long-term follow-up of pulmonary function in bronchial asthma patients treated with pranlukast.

Clinical studies have shown that pranlukast, a selective cysteinyl leukotriene antagonist, is effective for bronchial asthma. In the present paper, we retrospectively analyzed long-term asthma control by pranlukast treatment in patients treated with inhaled corticosteroids. We analyzed medical records and asthma diaries of 21 patients (9 males, 12 females) (52.1 +/- 3.5 years of age) with bronchial asthma who experienced increase of more than 10 L/min in peak expiratory flow in the first 4 weeks of treatment with pranlukast (450 mg/day) and were subsequently treated with pranlukast for more than 1 year. They all received inhaled corticosteroids (400-1600 microg/day of beclomethasone dipropionate or equivalent). We examined clinical control in terms of time course of self-monitored peak expiratory flow. During the analyzed period, the dose of inhaled corticosteroids was tapered in 4 patients, constant in 15 patients and increased in 2 patients. In 19 patients treated with unchanged or tapered dose of inhaled corticosteroids, improvement in the increase of mean PEF at 4-week treatment was maintained for 1 year. No difference in the add-on effect of pranlukast was observed in patients treated with less than 800 microg and more than or equal to 800 microg of inhaled corticosteroids. Four patients underwent reduction of inhaled corticosteroids in the analyzed period and PEF was well-maintained and even increased by pranlukast treatment. In 11 patients in whom data for 3 years were available, the improvement in PEF persisted for 3 years. Although the present investigation is a retrospective analysis, these data may suggest that pranlukast has no tachyphylaxis and its effect continues for more than 1 year.

[Epidemiologic study of admitted children with Kawasaki disease in Beijing from 1995 to 1999].

OBJECTIVE: To evaluate the epidemiologic picture of Kawasaki disease (KD) in Beijing and its suburbs. METHODS: A questionnaire form and diagnostic guideline for KD were sent to all hospitals with pediatric inpatient beds throughout Beijing and its suburbs. Pediatricians were asked to review the medical records and report all patients with KD diagnosed during the 5-year period from January, 1995, to December, 1999. RESULTS: A total of 710 patients with KD were reported from 37 (95%) of 39 hospitals with pediatric inpatient beds. The incidence rates of KD were 18.2 (1995), 21.1 (1996), 18.6 (1997), 30.6 (1998) and 27.8 (1999) per 100,000 children < 5 years of age. The male:female ratio was 1.7:1. The age at onset ranged from 1 month to 13.4 years (with median of 2.3 years), with 85.2% < 5 years old. The disease occurred more frequently in spring and summer and less frequently in autumn and early winter. Lymph node enlargement was the least common clinical sign, and its incidence decreased from 1995 to 1999. Cardiac abnormalities were found in 21.5% of patients and were more prevalent in patients diagnosed 10 days or longer after the onset. No patients died in the acute stage. CONCLUSIONS: The incidence of KD in Beijing is lower than that reported in Japan, similar to the incidence in the United States and higher than in those other Western countries. The age and gender distribution and increasing trend in incidence are similar to those in previous reports, but seasonal distribution is unique.

Add-on effects of suplatast tosilate in bronchial asthma patients treated with inhaled corticosteroids.

Th2 cytokines play an important role in the pathogenesis of asthma. In the present study, we investigated the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control, in terms of subjective symptoms and pulmonary function in patients treated with inhaled corticosteroids. Thirty-eight patients with bronchial asthma being treated with inhaled corticosteroids were given suplatast tosilate (100 mg three times daily) for 12 weeks, in a multicenter setting. During the study period, other medications were continued. Morning and evening peak expiratory flow, asthma symptoms, blood eosinophil count and serum IgE levels were monitored. Suplatast tosilate treatment was associated with a significant improvement in mean morning peak expiratory flow (from 295 L/min to 348 L/min, P < 0.01) and evening peak expiratory flow (from 313 L/min to 357 L/min, P < 0.01). The mean daily variation in peak expiratory flow was significantly reduced (from 11.6% to 7.3%, P < 0.01) by suplatast tosilate treatment. The greatest improvement in peak expiratory flow was observed in patients whose blood eosinophil counts were decreased by suplatast tosilate treatment. Treatment with suplatast tosilate improved pulmonary function in patients with bronchial asthma. Our results suggest the therapeutic effects observed may occur through suppression of eosinophilic inflammation.

Kawasaki disease in parents and children.

AIM: To estimate the probability that the parents of patients with Kawasaki disease also had a history of the same disease. METHODS: Self-reported parents' histories of Kawasaki disease were collected from data of the 16th nationwide survey of the disease conducted in Japan from January 1999 to December 2000. The incidence of Kawasaki disease was calculated by using data reported in all 16 nationwide surveys and live births in the Japanese vital statistics. The expected number of parents with a history of Kawasaki disease in the general population, which was calculated by using the assumed number of parents in the vital statistics and the incidence of this disease, was compared with the observed number. RESULTS: Among 14,163 parent pairs of patients with Kawasaki disease, 33 parents (25 mothers and 8 fathers) had a history of the disease. The number of parents expected to have a history of Kawasaki disease was 16.1 (8.4 mothers and 7.7 fathers). From a Poisson distribution, the probability of the observed number was less than 0.001 among parents or mothers. The prevalence of a recurrence of Kawasaki disease and incidences involving siblings of patients whose parents had a history of the disease were five or six times higher than those of all patients who were reported in the 16th survey. CONCLUSION: When compared with parents in the general population, the probability of a history of Kawasaki disease was significantly higher in those parents whose children suffered from the same disease. This suggests that, epidemiologically, a genetic predisposition to Kawasaki disease may be implicated in its occurrence.

Adenoviral interleukin-12 gene transduction into human bronchial epithelial cells: up-regulation of pro-inflammatory cytokines and its prevention by corticosteroids.

BACKGROUND: One of the potential effects of IL-12 is to restore Th1/Th2 balance. Therefore, we investigated the possibility of developing a system for local delivery of IL-12 into the airways by examining protein expression in a human bronchial epithelial cell line (BEAS-2B) after adenoviral IL-12 gene transduction. The effects of dexamethasone on the gene-modified cells were also examined. METHODS: Adenoviral vectors AxCAegfp and Ax1CIhp40ip35 were used to transduce enhanced green fluorescence protein and IL-12 genes, respectively, into BEAS-2B cells. Wild-type and IL-12 gene-transduced BEAS-2B cells were then incubated with or without dexamethasone, and concentrations of IL-12, IFN-gamma, IL-6, IL-8, granulocyte macrophage-colony stimulating factor and chemokines (TARC and RANTES) in the supernatant were measured by ELISA. IL-12 receptor expression was analysed by flow cytometry and RT-PCR. RESULTS: The efficiency of transgene expression in BEAS-2B cells at a multiplicity of infection of 30 was approximately 80%. Gene-modified BEAS-2B cells produced biologically active IL-12, regardless of dexamethasone treatment. While IL-12 gene transduction led to increased production of IL-6 and IL-8 by BEAS-2B cells, expressions of these proteins were suppressed by dexamethasone. Addition of exogenous IL-12 failed to augment BEAS-2B cell IL-6 and IL-8 production, and IL-12 receptor expression by BEAS-2B cells was not detected. CONCLUSIONS: Our findings suggest that adenoviral IL-12 gene transduction may be effective in inducing IL-12 expression in the airways, and could be a potential approach in the management of bronchial asthma.

Factors relating to the cardiac sequelae of Kawasaki disease one month after initial onset.

UNLABELLED: This study aimed to determine the risk factors related to the presence of cardiac sequelae 1 mo after initial onset and to examine the preventive effect of the early administration of high-dose gamma-globulin (GG) on cardiac sequelae in patients with Kawasaki disease. Patients treated with high-dose GG of 2000 +/- 100 mg kg(-1) were selected as subjects from the 15th nation-wide survey in Japan. Univariate and logistic multiple variable analyses were used to test the effects of background variables such as age and gender, variables relating to laboratory findings such as the percentage of neutrophil leucocytes, and variables relating to the GG treatment on the presence of cardiac sequelae. The odds ratios were significantly higher for males (1.48), those younger than 1 y of age (1.71), recurrent cases (2.42), and those with a low haematocrit (<32.5%) (1.45) and high percentage of neutrophil leucocytes (>68%) (1.63). The odds ratio was low for those who started GG administration in less than 6 d from onset between the patients with and without cardiac sequelae. The odds ratio for the duration of GG treatment was not significantly different between those with and without cardiac sequelae. CONCLUSION: Patients who received early administration of GG, less than 6 d from onset of the disease, had a lower risk than those received GG more than 6 d from the onset. The percentage of neutrophil leucocytes and the haematocrit level are useful indicators in predicting the development of cardiac sequelae.

[Relationship between skipping breakfast and cardiovascular disease risk factors in the national nutrition survey data].

PURPOSE: To investigate the relationship between skipping breakfast and cardiovascular disease risk factors such as blood pressure, serum lipids, smoking, and lock of exercise. MATERIALS AND METHODS: Data from the National Nutrition survey conducted by the Ministry of Health and Welfare, from 1995 through 1997 were employed for the analysis. Data were used only if subjects were between 20 and 59 years old and had participated in the nutrition survey, and values for height and weight, blood pressure, serum lipids, blood sugar, number of steps per day, and smoking, drinking, and exercise habits were available. The number of subjects with data available for all of the above was 11,778 (4,438 men and 7,340 women). Analyses were performed separately by sex. The relationship between skipping breakfast and continuous variables such as nutrient intake ratio (nutrient intake divided by recommended dietary allowances), body mass index, blood pressure, serum lipids, blood sugar, and the number of steps per day was examined controlling for age using analysis of covariance (ANCOVA). The relationship between skipping breakfast and categorical variables such as smoking, drinking, and exercise habits was assessed controlling for age using Cochran-Mantel-Haenszel statistics. RESULTS: The younger the generation, the higher the rate of skipping breakfast. The rate of skipping breakfast in men was twice as high as in women. The breakfast skippers tended to intake less energy and calcium, both in men and women, that non-skippers. Female skippers tended to intake less iron and vitamin D. The number of steps per day was smaller in breakfast skippers than that in non-skippers both in men and women. Male skippers tended to have higher blood pressure than non-skippers, and female skippers tended to have a higher serum total cholesterol level than non-skippers. The breakfast skippers tended to smoke more than non-skippers, both in men and women, and female skippers tended to drink more alcohol and take less exercise. CONCLUSIONS: Skipping breakfast is related to cardiovascular risk factors such as lack of exercise, smoking, high blood pressure, and high serum total cholesterol.

Random multi-recombinant PCR for the construction of combinatorial protein libraries.

Development of a new methodology to create protein libraries, which enable the exploration of global protein space, is an exciting challenge. In this study we have developed random multi-recombinant PCR (RM-PCR), which permits the shuffling of several DNA fragments without homologous sequences. In order to evaluate this methodology, we applied it to create two different combinatorial DNA libraries. For the construction of a 'random shuffling library', RM-PCR was used to shuffle six DNA fragments each encoding 25 amino acids; this affords many different fragment sequences whose every position has an equal probability to encode any of the six blocks. For the construction of the 'alternative splicing library', RM-PCR was used to perform different alternative splicings at the DNA level, which also yields different block sequences. DNA sequencing of the RM-PCR products in both libraries revealed that most of the sequences were quite different, and had a long open reading frame without a frame shift or stop codon. Furthermore, no distinct bias among blocks was observed. Here we describe how to use RM-PCR for the construction of combinatorial DNA libraries, which encode protein libraries that would be suitable for selection experiments in the global protein space.

Efficient generation of dendritic cells from alveolar and pleural macrophages as well as blood monocytes in patients with lung cancer.

In this study, we investigated the generation of dendritic cells (DCs) from blood monocytes and mature macrophages from untreated primary lung cancer patients. Blood monocytes were separated by adherence from blood mononuclear cells (MNC) from ten lung cancer patients and ten control subjects, and cultured for 7 days in medium with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL-) 4. In all cases examined, DCs with typical characteristics were obtained even in lung cancer patients after 7 days culture with these cytokines, and there was no significant difference in phenotype and stimulatory activity in allogeneic lymphocyte proliferation between DCs derived from monocytes from lung cancer patients and those from control subjects. Next, we examined whether alveolar and pleural macrophages in malignant pleural effusion separated by magnetic beads could differentiate to immunostimulatory DCs. Conventional culture conditions with GM-CSF and IL-4 did not induce efficient numbers of DCs from mature macrophages, whereas the addition of tumor necrosis factor-alpha (TNF-alpha) to GM-CSF and IL-4 effectively contributed to generate DCs. These findings suggest that both mature macrophages and blood monocytes from lung cancer patients could differentiate to DCs, and might be a useful source of DCs for immunotherapy.

Genotype-phenotype linkage for directed evolution and screening of combinatorial protein libraries.

The technologies for screening peptide and protein libraries for studies in the fields of directed protein evolution and functional genomics have advanced with astonishing speed. For screening of functional proteins, three technologies are required: (i) the construction of a gene library (genotype), (ii) the establishment of a linkage between each protein (phenotype) and its encoding gene (genotype), and (iii) the selection of desired proteins (phenotype) from the library. This review highlights the genotype-phenotype linkage technologies, which can be classified into three types; that is, cell-type linkage, virus-type linkage, and array-type linkage methods. These methods are summarized, and their advantages and disadvantages are discussed.

The profiles of Kawasaki disease in China.

Kawasaki disease in China was described for the first time in 1976 in Taiwan, and in 1978 in mainland, respectively. Questionnaire surveys had been conducted in both of the area of China and showed that the Kawasaki disease patients increased year by year. No data on incidence rates were available for these surveys because the problem of representativeness. However, it showed that there were many similar characteristics of Kawasaki disease in China comparing with those in Japan. Although a series of infectious agents were suspected, the etiology of Kawasaki disease remained unclear. High dose of gamma globulin treatment was also adopted commonly in China.

Protein anatomy: structure and function of peptide fragments corresponding to the secondary structure units of barnase.

Globular proteins can be decomposed into several modules or secondary structure units. It is useful to investigate the functions of such structural units in order to understand the folding units of proteins. In our previous work, barnase was divided into six peptide fragments corresponding to modules, and some of them were shown to have RNA-binding and RNase activity [Yanagawa, et al. (1993) J. Biol. Chem. 268, 5861-5865]. Barnase mutant proteins obtained by permutation of the structural units also had RNase activity [Tsuji, T. et al. (1999) J. Mol. Biol. 286, 1581-1596]. Here we investigated the structure and function of peptide fragments corresponding to secondary structure units of barnase. The results of circular dichroism spectroscopy indicated that some of the peptide fragments form helical structures in aqueous solutions containing over 30% 2,2,2-trifluoroethanol, and the S6 (94-110) peptide fragment is induced to form a beta-sheet structure in the presence of RNA. The S6 peptide fragment forms aggregate complexes with RNA. Electron microscopic analysis showed that the aggregate complexes were comprised of filaments. These results indicate that not only modules but also secondary structure units dissected from a globular protein have functional and structure-forming capabilities.

[Bullous sarcoidosis--a case report].

A 37-year-old man was admitted to our hospital complaining of dry cough and dyspnea. His chest radiographs showed severe bullous changes in the upper lobes and scattered small nodules in the lower. During the course of further examination, a spontaneous left pneumothorax developed in the lung, and video-assisted thoracic surgery was performed to remove a bulla. Multiple noncaseous granulomas were seen and sarcoidosis was diagnosed. Here we report a case of pathologically investigated bullous sarcoidosis, which is rarely seen to generate bullae due to granulomatous lesions. Therefore, it is important to consider sarcoidosis in making a differential diagnosis when a diffuse lung disease with cystic change is encountered.

CD40 and IFN-gamma dependent T cell activation by human bronchial epithelial cells.

We examined whether freshly isolated human bronchial cells (HBEC) and bronchial epithelial cell line/BEAS-2B cells expressed surface molecules required for APC function. These cells expressed CD40 and ICAM-1, but not B7-1, B7-2 or HLA-DR molecules. Treatment of these cells with IFN-gamma resulted in enhanced expression of CD40 and ICAM-1 as well as induction of HLA-DR expression. Th2 cytokines such as IL-4 and IL-5, proinflammatory cytokine of GM-CSF and nonspecific activator endotoxin had no effect on these phenotypic expressions. Functional examinations showed that allogeneic lymphocytes purified from peripheral blood strongly proliferated in response to BEAS-2B cells cultured with IFN-gamma, but only weakly compared with those without IFN-gamma. When allogeneic lymphocytes were purified to CD4+ cells, the proliferative response against BEAS-2B cells was abolished. Blockade of CD40-CD40L interaction by anti-CD40 antibody also inhibited the proliferation of lymphocytes to BEAS-2B cells, although this treatment showed a minimum effect on the response to allogeneic MNC. Thus, bronchial epithelial cells have the ability to present allogeneic antigens to T cells in both CD40- and IFN-gamma-dependent manners under the presence of third party cells that transduce co-stimulatory signals.

Incidence rate of recurrent Kawasaki disease and related risk factors: from the results of nationwide surveys of Kawasaki disease in Japan.

UNLABELLED: To investigate the incidence of recurrent Kawasaki disease, and to discuss some of the potential risk factors, data of the 13th and 14th nationwide surveys of Kawasaki disease in Japan were analyzed. To calculate the rate of recurrence, 10679 patients with 31501.9 person-years were observed. The mean observation period was 2.95 y. The rate of recurrence was 6.89 per 1000 person-years, with a high incidence within the 12 mo following the first episode. CONCLUSION: The incidence was high among those under 3 y of age and those with cardiac sequelae during the first episode. None of the other factors affected the incidence.