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PubMed2004

[Subset analysis of data in the Japanese patients with NSCLC from IDEAL 1 study on gefitinib].

The multinational, multi-institutional clinical Phase II trial of gefitinib monotherapy, IDEAL (IRESSA Dose Evaluation in Advanced Lung Cancer) 1, included Japanese and non-Japanese patients with advanced non-small-cell lung cancer (NSCLC) pretreated with one or more chemotherapy regimens, at least one including platinum. To investigate whether survival is affected by gender or histological type of cancer, a retrospective, exploratory subset analysis was conducted including only Japanese patients from IDEAL 1 (n = 102 in total, 51 each in 250 and 500 mg/day groups). The median survival time of the 102 patients was 12.0 months and the one year survival rate was 50%. The median survival time was 13.8 months for the 250 mg/day group and 11.2 months for the 500 mg/day group and the one-year survival rate was 57% and 45% respectively. Survival was longer in patients with adenocarcinoma than those with other histological types of cancer, and was longer in those with symptom improvement than without. The median survival time in females was longer than that in males. The results suggest that gefitinib could be superior to classical anticancer agents with regard to not only the response rate but also survival time in patients with NSCLC, particularly adenocarcinoma, previously treated with chemotherapy. Further studies are needed to identify factors affecting survival.

Adult↗
PubMed1991

[Organ transplantation and laboratory tests].

The media has recently been featuring organ transplantation from various viewpoints. Furthermore, Novel Prizes 1990 for Medical & Physiological fields were awarded to Drs. JE Murray and ED Thomas, both pioneers of clinical transplantation. Our topic has been timely indeed. This symposium mainly dealt with laboratory tests vs. various types of organ transplantation. In reality though, only kidney and bone marrow transplantations have been practiced in Japan; thus, Dr. I Yokoyama, University of Pittsburgh, discussed liver transplantation. First, Dr. K Uchida lectured on the recent advancement of immunosuppressive drugs and improvement in the clinical outcome of kidney transplantation. Serum creatinine determination is the only parameter for rejection besides renal biopsy. Drs. K Miyamura & Y Morishima discussed about PCR method to detect MRD (minimal residual diseases). There are positive relationships between the remaining leukemic cells and the relapse of leukemia even though the patients are in clinical remission. Dr. H Funada dealt with the importance of "sterile room treatment" for bone marrow transplantation. It protects patients from infection, minimizes GVHD and prolongs survival time after transplantation. Dr. Yokoyama stressed the importance of back-up system, i.e. drug-monitoring, coagulation tests, pathological examination, biochemical tests, blood transfusion services for successful liver transplantations. Dr. T Fukunishi discussed the importance of developing the organ donor and coordinator system to promote kidney transplantation from cadaver. He also dealt with virus antibody tests for selecting donors. All discusssions stressed on the importance of the 24-hour laboratory back-up system performing emergency tests but no specific laboratory test for organ transplantation was necessary.

Clinical Laboratory Techniques↗
PubMed2006

A prospective, double-blind, randomized trial of caudal block using ropivacaine 0.2% with or without fentanyl 1 microg kg-1 in children.

BACKGROUND: It has been reported that ropivacaine produces vasoconstriction in contrast to vasodilation produced by bupivacaine. It is possible that additives to ropivacaine can provide further analgesic advantages compared with bupivacaine. We thus evaluated whether the addition of fentanyl to ropivacaine prolonged the duration of analgesia after a single shot caudal block. METHODS: A total of 36 children undergoing surgical procedures below the umbilicus were randomly allocated to one of two groups: Group F received ropivacaine 0.2%, 1 ml kg(-1) with fentanyl 1 microg kg(-1) and Group S received ropivacaine 0.2%, 1 ml kg(-1) with saline. The analgesic effect of the caudal block was evaluated using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and sedation was assessed using the Steward score at 30 min after extubation and at 1, 2, 4, 6, 12 and 24 h. The first analgesic requirement time and side-effects in a 24 h period were also recorded. RESULTS: There were no differences in characteristics between the groups. The end-tidal concentration of sevoflurane at extubation in Group F was significantly lower than in Group S. However, there was no significant difference in time from discontinuation of the volatile anaesthetics to tracheal extubation. No statistical differences were found in the CHEOPS and Steward score, and the time to first analgesia. The incidence of postoperative vomiting was not significantly different. CONCLUSION: We found that the addition of fentanyl 1 mug kg(-1) to ropivacaine 0.2% for caudal analgesia provides no further analgesic advantages over ropivacaine 0.2% alone.

Amides↗
PubMed1995

4-Hydroxy-2-nonenal-trapping ELISA: direct evidence for the release of a cytotoxic aldehyde from oxidized low density lipoproteins.

Among the aldehydes that originate from the peroxidation of cellular membrane lipids, 4-hydroxy-2-nonenal (HNE) is thought to be largely responsible for cytopathological effects observed during oxidative stress. Taking advantage of the fact that HNE is very reactive with proteins and forms stable Michael addition-type adducts, a novel immunochemical procedure for quantifying "free" HNE has been developed. The method designated as "HNE-trapping ELISA" is based on the detection of HNE trapped by a protein that has been coated in the immunoplate. The HNE-derived epitopes generated in the coating protein are then detected by the ELISA using a monoclonal antibody (mAbHNEJ-2) specific to the haptenic groups of the HNE-protein conjugates. Using this method, we determined that a considerable amount of HNE was released from human plasma low density lipoproteins (LDL) treated with copper ions or endothelial cells.

Aldehydes↗
PubMed1993

Mouse brain opioid receptor identification by direct ultraviolet photoaffinity labeling.

[3H]Morphine, PL-017[prolyl-3,4-3H,D-prolyl,3,4-3H] ([3H]PL-017) and enkephalin-(2-D-penicillamine,5-D-penicillamine)[tyrosyl-2,6-3H] ([3H]DPDPE) were directly cross-linked to mouse brain opiate receptors by an ultraviolet (254 nm) irradiation procedure. [3H]Morphine preferentially and specifically labeled a 58 kDa protein. The labeling of this protein was suppressed by the addition of excess naloxone. Dithiothreitol reduced the irreversible binding of [3H]morphine and [3H]PL-017 to the receptor protein. In the acid hydrolysate of [3H]DPDPE-labeled opiate receptors, dityrosine, was detected. These results suggest that the [3H]tyrosine residue of [3H]DPDPE covalently bound the tyrosine residue of delta-opioid receptors. The direct UV-photoaffinity labeling method using commercially available radioactive opiates described here should be a useful tool for characterization and purification of the opiate receptors.

Affinity Labels↗
PubMed1997

Postischemic accumulation of lipid peroxidation products in the rat brain: immunohistochemical detection of 4-hydroxy-2-nonenal modified proteins.

We report an immunohistochemical study on the distribution and alterations of 4-hydroxy-2-nonenal (HNE)-modified proteins, an indicator of lipid peroxidation, in the rat brain after 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion. HNE immunoreactivity was not observed in intact neurons, but it appeared in some shrunken neurons within the infarcted zone at 3 h after reperfusion. The number of HNE-positive neurons increased with the spread of the infarcted area. The pyramidal neurons in the third layer of the frontoparietal cortex were HNE-positive and the intensity of their HNE immunoreactivity was highest at 24 h after reperfusion. At 48 h, HNE-positive neurons were observed in the medial part of the striatum, the lateral side of the frontoparietal cortex, and at the boundary between the infarcted and noninfarcted zones. In addition, strong HNE immunoreactivity was seen in microglia (identified by OX-42 immunostaining). This method seems to be useful to follow the progress of lipid peroxidation at the cellular level after ischemic injury.

Animals↗
PubMed2002

A simple method of detecting K-ras point mutations in stool samples for colorectal cancer screening using one-step polymerase chain reaction/restriction fragment length polymorphism analysis.

BACKGROUND: We examined a technique for detecting point mutations of K-ras codon 12 in stool samples using one-step polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis, in order to determine whether it could be used to screen for colorectal cancer. METHODS: DNA was extracted from 200-mg stool specimens of 5 healthy controls and 31 colorectal cancer patients. A 107-base-pair fragment of exon 1 of K-ras was amplified by PCR using mismatched primers. PCR products were digested with Bst NI and analyzed by gel electrophoresis followed by silver staining. Specificity of one-step PCR/RFLP was examined by using synthetic oligonucleotides. The detection limit of K-ras codon 12 mutations was determined by using SW480 and HT29 cells. RESULTS: The K-ras gene was successfully amplified from all healthy controls and colorectal cancer patients studied. Mutations of K-ras codon 12 were not detected in any of the healthy controls, but were identified in 13 (41.9%) of the 31 patients with colorectal cancer. Mutations were detectable in all six synthetic mutant DNAs, while none were detected among the wild type. The detection limit of this method was > or = 0.1%. CONCLUSIONS: PCR/RFLP analysis could be used in mass screening for colorectal cancer, because it is highly specific, has a low detection limit, and is simpler than conventional methods for detecting genetic abnormalities.

Adult↗
PubMed2003

Erosion of water-based cements evaluated by volumetric and gravimetric methods.

OBJECTIVES: To compare the erosion of glass ionomer, zinc phosphate and polycarboxylate cements using volumetric and gravimetric methods. METHODS: For the volumetric method, the eroded depth of cement placed in a cylindrical cavity in PMMA was measured using a dial gauge after immersion in an eroding solution. For the gravimetric method, the weight of the residue of a solution in which a cylindrical specimen had been immersed was measured. 0.02 M lactic acid solution (0.02 M acid) and 0.1 M lactic acid/sodium lactate buffer solution (0.1 M buffer) were used as eroding solutions. The pH of both solutions was 2.74 and the test period was 24 h. RESULTS: Ranking of eroded depth and weight of residue was polycarboxylate>zinc phosphate>glass ionomers. Differences in erosion were more clearly defined by differences in eroded depth than differences in weight of residue. In 0.02 M acid, the erosion of glass ionomer using the volumetric method was effected by the hygroscopic expansion. In 0.1 M buffer, the erosion for polycarboxylate and zinc phosphate using the volumetric method was much greater than that using the gravimetric method. This is explained by cryo-SEM images which show many holes in the surface of specimens after erosion. It appears that zinc oxide is dissolved leaving a spongy matrix which easily collapses under the force applied to the dial gauge during measurement. SIGNIFICANCE: The volumetric method that employs eroded depth of cement using a 0.1 M buffer solution is able to quantify erosion and to make material comparisons.

Buffers↗
PubMed1999

Identification and selective perfusion of the spinal cord-feeding arteries by intrathecal pO2 monitoring for spinal cord protection.

OBJECTIVES: to study whether spinal cord-feeding arteries could be identified by the changes in the intrathecal pO2 (I-pO2), and to examine whether selective perfusion of feeding arteries identified by this method could protect the spinal cord against ischaemia. DESIGN: controlled animal experiments. MATERIALS AND METHODS: in experiment 1, using 16 mongrel dogs, 18 segmental arteries were cannulated through which oxygenated saline was injected and the I-pO2 change was observed. When the I-pO2 increase was more than 0.5 mmHg, the artery was considered to be a spinal cord-feeding artery. In experiment 2, involving 10 dogs, the segmental arteries identified as spinal cord-feeding arteries were perfused with arterial blood and the recovery of I-pO2 and evoked spinal potentials (ESP) was examined. RESULTS: of 208 segmental arteries examined, 176 (84.6%) arteries were correctly judged and 32 (15.4%) were not. It was observed that the I-pO2 recovered from 13.9 to 30.5 mmHg and the ESP recovered from 20.9% and 8.2% to 66.5% and 44.7% of each control for the first negative (N1) and second negative (N2) components, respectively. CONCLUSION: spinal cord-feeding arteries were successfully identified using the I-pO2 monitoring method. Perfusion of these arteries with arterial blood improved the I-pO2 and ESP, which were significantly depressed by ischaemia.

Animals↗
PubMed2005

A novel mycological analysis valuable for evaluating therapeutic efficacy of antimycotics against experimental dermatophytosis in guinea pigs.

Although antimycotic effects are mainly evaluated with regard to whether or not the fungi grow from a specimen obtained from the drug-treated skin, the potential for discrepancies in skin specimens in which the fungi are grown has not been evaluated, in the experimental tinea model. In this study, to evaluate the therapeutic effectiveness of antimycotic agents against fungal skin infection, a novel form of mycological assessment, which focuses on the size of colonies grown from skin specimens was examined and developed. When microconidia of Trichophyton mentagrophytes were inoculated onto a Sabouraud dextrose agar (SDA) plate and incubated at 27 degrees C for 5 days, a linear relationship was observed between the growth area of mycelia and the logarithm of the quantity of microconidia. This relationship between the growth area and the logarithm of the number of T. mentagrophytes microconidia did not change with the addition of skin homogenate and/or keratin powder. Next, the number of fungi in skin blocks attendant upon experimental, cutaneous infection in guinea pigs was evaluated and analyzed via a calibration curve, determined based on a microconidium suspension of T. mentagrophytes. Estimates of severity of dermatophytic infection in experimental animals were parallel to, but more reliable than, results obtained via the conventional mycological method (fungus-positive skin ratio of treated skin) in culture studies of infected dermal tissues. This new analytical method may also be applicable to the in vivo assessment of the therapeutic effect against dermatophytosis experimentally produced in guinea pigs.

Animals↗
PubMed2003

Treatment of nevus using medical tattooing.

Medical tattooing is used to color skin with a pigment loss. Currently, however, a trial-and-error scheme is employed to obtain the desired color appearance of tattooed skin because prediction of the color appearance is dependent on the experiences of medical doctors. We propose a method for predicting the color appearance of tattooed skin. Two trial dyes are first injected in the area of pigment loss, and the color appearance of a third dye to be injected can be predicted using measured spectrocolorimeter data and mathematical formula. The spectrocolorimeter measures the color appearances of the skin before and after tattooing using the first two dyes, and the mathematical formula calculates the color appearance of the tattooed skin using any third dye. In the derivation of the mathematical formula, light propagation in the skin has been modeled using the modified Lambert-Beer law considering the strong scattering of light by biological tissues. The proposed method was successfully validated by a preliminary tattooing of the skin to an area with pigment loss. Predicting the color appearance of tattooed skin significantly reduces the number of trial-and-error attempts required in the current methods. Medical tattooing using this method can also be applied to treat various skin color abnormalities such as leukoderma, intradermal nevi, and reconstructed nipples.

Colorimetry↗
PubMed2006

A new evaluation method for lumbar spinal instability: passive lumbar extension test.

BACKGROUND AND PURPOSE: Although many studies have described clinical examination measures for the diagnosis of lumbar spinal instability, few of them have investigated the sensitivity and specificity of the measures that were used. The authors devised a passive lumbar extension (PLE) test for assessing lumbar spinal instability. The purpose of this study was to investigate the sensitivity, specificity, and positive likelihood ratio of this test. SUBJECTS AND METHODS: The PLE test as well as the instability catch sign, painful catch sign, and apprehension sign tests were done for 122 subjects with lumbar degenerative diseases. The subjects were divided into 2 groups-instability positive and instability negative-on the basis of findings on flexion-extension films of the lumbar spine. The sensitivity, specificity, predictive values, and positive likelihood ratio of each test were investigated. RESULTS: The sensitivity and specificity of the PLE test were 84.2% and 90.4%, respectively. These values were higher than those of other signs. The positive likelihood ratio of the PLE test was 8.84 (95% confidence interval=4.51-17.33). DISCUSSION AND CONCLUSION: The PLE test is an effective method for examining patients for lumbar spinal instability and can be performed easily in an outpatient clinic.

Adult↗
PubMed1991

[Blood flow measurement of brain tumor by 123I-IMP using 3-heads rotating gamma camera SPECT].

Using 3-heads rotating gamma camera SPECT system, regional blood flow was measured from the super-early image obtained 4 to 6 minutes after the intravenous injection of 123I-IMP on 11 patients with various brain tumors. Two cases of olfactory groove meningioma and malignant astrocytoma showed significantly high 123I-IMP uptake by the lesion visualized by MRI compared to the uptake by normal brain cortex on super-early image but 123I-IMP uptake by the tumor decreased on early image. In both cases, blood flow of the tumor measured from super-early image showed values much higher than those of normal brain cortex. It was thought that usual correction method based on early image did not correctly represent the blood flow of the lesion but that the present method based on super-early image could show the increase of blood flow of the tumor.

Adult↗
PubMed1998

Inhaled corticosteroid reduced lamina reticularis of the basement membrane by modulation of insulin-like growth factor (IGF)-I expression in bronchial asthma.

BACKGROUND: Pathological studies of bronchial biopsy specimens have confirmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective in modifying airway inflammation. However, there is not much data on the effects of corticosteroid-treatment on the basement membrane. OBJECTIVE: To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the bronchial mucosa, and the expression of growth factors in patients with asthma. METHODS: We studied bronchial biopsies from 24 asthmatic patients before and after treatment with inhaled BDP, 400 microg twice a day or placebo, for 6 months in a double-blind manner. Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expression of growth factors were examined by immunohistochemistry in endobronchial biopsy specimens. RESULTS: After 6 months of treatment, we observed a significant improvement of asthma symptoms (P<0.01), PEF (P<0.01), diurnal variation of PEF (P<0.05), and airway responsiveness (P< 0.05) in the BDP group compared with the placebo group. This was accompanied by a significant decrease in the thickness of the lamina reticularis (P < 0.001), and in the number of activated eosinophils (P<0.01), T-lymphocytes (P<0.01), and fibroblasts (P < 0.05) in BDP-treated patients. There was also a reduction in the expression of insulin-like growth factor (IGF)-I (P < 0.01). Significant correlation was found between the IGF-I expression and collagen thickening (rs = 0.34, P<0.01), and the number of fibroblasts (rs = 0.45, P < 0.01). CONCLUSION: These results suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with consequent inhibition of the airway infiltration by inflammatory cells, and therefore may help to prevent remodelling of the airways.

Administration, Inhalation↗
PubMed1991

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans.

The effects of grapefruit juice (150 ml at -15, -10, -1/4, +5, and +10 hours) and cimetidine (200 mg at the same times) on the stereoselective pharmacokinetics and effects of 20 mg oral racemic nitrendipine were investigated in a placebo-controlled crossover study in nine healthy men. In all subjects the AUC of racemic nitrendipine was increased by grapefruit juice (mean increase 106%; 95% confidence interval 64% to 158%) and cimetidine treatment (+154%; 95% confidence interval 77% to 265%). Comparable results were obtained for the peak plasma drug concentration and for both parameters of (S)- and (R)-nitrendipine. There were highly significant differences in the area under the concentration-time curve and peak plasma drug concentration between enantiomers within all treatments. Grapefruit juice had no effect on this stereoselectivity, but cimetidine increased the mean S/R ratio of areas under the curve (2.25) by 20% (95% confidence interval 12% to 29%) compared with placebo treatment (1.89). Half-lives and time to reach peak concentration of the enantiomers were not different within and between treatments. There were no consistent effects on blood pressure with all treatments, but in most subjects there was a small temporary increase in heart rate after intake of nitrendipine. Grapefruit juice and cimetidine did not affect these hemodynamic parameters and did not cause additional adverse effects.

Adult↗