A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Gastric functional monitoring by gastric electrical impedance tomography (gEIT) suit with dual-step fuzzy clustering.

Gastric Function has been successfully estimated by gastric electrical impedance tomography (gEIT) Suit with dual-step fuzzy clustering. The gEIT Suit which are made of elastic cloth with dual-planar electrodes and compact data acquisition (DAQ) system measures gastric impedance Z to visualize the gastric conductivity distribution σ. The dual-step fuzzy clustering extracts the clustered gastric conductivity distribution kσ, which accurately estimates the gastric function. The gEIT Suit with dual-step fuzzy clustering are applied to eight healthy persons during liquid meal consumption to estimate the gastric function under gastric accommodation phase of 200, 400 and 600 mL based on the gastric emptying phase. As the results, the gEIT Suit successfully estimate the gastric function. By the measured impedance Z, the subjects have a mean temporal impedance [Formula: see text]= - 9.27 [Ohm] and p-value of that [Formula: see text] p(Z) = 0.0013[-]as the t-test result. In the case of gastric conductivity distribution σ, the subjects have a value of spatial mean conductivity distribution ⟨σ⟩ = 0.23[-] and p-value of that ⟨σ⟩ p(σ) = 0.0140[-]. Lastly, in the case gastric volume V, subjects have a gastric volume V = 12.44 [%] and p-value p(V) = 0.0664[-].

Correlation between alterations in blood flow of malignant lymphomas after induction chemotherapies and clinical outcomes: a pilot study utilising contrast-enhanced ultrasonography for early interim evaluation of lymphoma treatment.

AIM: To clarify the utility of contrast-enhanced ultrasonography (CEUS) for interim evaluation of response to chemotherapy in lymphoma treatment. MATERIALS AND METHODS: CEUS was performed both before (day 0) and after the treatment (7 and/or 14 days), and a time-intensity curve was obtained. The patients were divided into two groups (complete remission [CR] group and non-CR group) according to the results of conventional response evaluation, and peak enhancement (PE), time to peak enhancement, perfusion index (PI), the total area under the curve during wash-in (AUC-in), and the total AUC were compared between the groups. RESULTS: Among 27 patients with various types of lymphoma, the median change ratio of PE and PI at day 7 evaluation were significantly different between the CR group and the non-CR group (0.81 versus 1.39, p=0.017 for PE and 0.92 versus 2.09, p=0.010 for PI). The change ratio of PE < 1.09 (specificity: 86%; sensitivity, 88%) and PI < 1.65 (specificity: 86%; sensitivity: 94%) distinguished CR from non-CR. Patients who achieved a PE change ratio <1.09 or a PI change ratio <1.65 had significantly better estimated progression-free survival (p<0.001). CONCLUSION: The present study demonstrated that changes in tumour perfusion parameters evaluated with CEUS at 1 week after the treatment initiation were significantly different between lymphoma patients in CR group and non-CR group. Alterations in perfusion parameters evaluated via CEUS could impact the prognosis of lymphoma patients.

Investigation of Physiological Swelling on Conductivity Distribution in Lower Leg Subcutaneous Tissue by Electrical Impedance Tomography.

There is a strong need for a non-invasive measurement technique that is capable of accurately identifying the physiological condition change or heterogeneity of subcutaneous adipose tissue (SAT) by localizing the abnormalities within the compartment. This paper aims to investigate the feasibility of Electrical Impedance Tomography (EIT) to assess the interstitial fluid in subcutaneous adipose tissue as an enhancement method of bioelectrical impedance spectroscopy (BIS). Here, we demonstrate the preliminary result of EIT with a wearable 16 electrodes sensor. The image-based reference EIT with fat weighted threshold method is proposed. In order to evaluate the performance of our novel method, a physiological swelling experiment is conducted, and Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is also applied as a comparison with EIT results. The experimental results showed that the proposed method was able to distinguish the physiological swelling condition and effectively to remove the unexpected background noise. Furthermore, the conductivity variation in the subcutaneous layer had a good correlation with extracellular water volume change from MFBIA data; the correlation coefficient R2 = 0.927. It is concluded that the proposed method provides a significant prospect for SAT assessment.

Impact of tocilizumab on N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis without cardiac symptoms.

OBJECTIVE: To prospectively investigate the effect of tocilizumab (TCZ) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), as a predictor of congestive heart failure (CHF) in patients with active rheumatoid arthritis (RA). METHOD: Seventy patients with RA (median age 59 years, 86% female) free of cardiovascular disease were treated with TCZ and followed for 24 weeks. The NT-proBNP levels were measured at baseline and week 24. Thirty healthy controls were included for comparison of normal NT-proBNP levels with those of RA patients. RESULTS: The NT-proBNP level was significantly higher in patients with RA than in controls (median 42.5 pg/mL vs 109.0 pg/mL, p < 0.001). NT-proBNP levels decreased by 63% over the 24 weeks of TCZ treatment. Multiple linear regression analysis indicated that the percentage change in the NT-proBNP level was significantly associated with that of the Simplified Disease Activity Index (ß = 0.356, p = 0.014), even after adjusting for the levels of rheumatoid factor, duration of RA, age, and anti-cyclic citrullinated peptide antibody. CONCLUSION: TCZ decreased the NT-proBNP level in patients with RA without preceding cardiovascular disease and CHF. TCZ may have a cardioprotective effect in those with active RA.

Development of three-dimensional integrated microchannel-electrode system to understand the particles' movement with electrokinetics.

An optical transparent 3-D Integrated Microchannel-Electrode System (3-DIMES) has been developed to understand the particles' movement with electrokinetics in the microchannel. In this system, 40 multilayered electrodes are embedded at the 2 opposite sides along the 5 square cross-sections of the microchannel by using Micro Electro-Mechanical Systems technology in order to achieve the optical transparency at the other 2 opposite sides. The concept of the 3-DIMES is that the particles are driven by electrokinetic forces which are dielectrophoretic force, thermal buoyancy, electrothermal force, and electroosmotic force in a three-dimensional scope by selecting the excitation multilayered electrodes. As a first step to understand the particles' movement driven by electrokinetic forces in high conductive fluid (phosphate buffer saline (PBS)) with the 3-DIMES, the velocities of particles' movement with one pair of the electrodes are measured three dimensionally by Particle Image Velocimetry technique in PBS; meanwhile, low conductive fluid (deionized water) is used as a reference. Then, the particles' movement driven by the electrokinetic forces is discussed theoretically to estimate dominant forces exerting on the particles. Finally, from the theoretical estimation, the particles' movement mainly results from the dominant forces which are thermal buoyancy and electrothermal force, while the velocity vortex formed at the 2 edges of the electrodes is because of the electroosmotic force. The conclusions suggest that the 3-DIMES with PBS as high conductive fluid helps to understand the three-dimensional advantageous flow structures for cell manipulation in biomedical applications.

Acotiamide Hydrochloride, a Therapeutic Agent for Functional Dyspepsia, Enhances Acetylcholine-induced Contraction via Inhibition of Acetylcholinesterase Activity in Circular Muscle Strips of Guinea Pig Stomach.

Acotiamide is a first-in-class prokinetic drug approved in Japan for the treatment of functional dyspepsia. Given that acotiamide enhances gastric motility in conscious dogs and rats, we assessed the in vitro effects of this drug on the contraction of guinea pig stomach strips and on acetylcholinesterase (AChE) activity in stomach homogenate following fundus removal. We also investigated the serotonin 5-HT4 receptor agonist mosapride, dopamine D2 receptor and AChE inhibitor itopride, and representative AChE inhibitor neostigmine. Acotiamide (0.3 and 1 µM) and itopride (1 and 3 µM) significantly enhanced the contraction of gastric body strips induced by electrical field stimulation (EFS), but mosapride (1 and 10 µM) did not. Acotiamide and itopride significantly enhanced the contraction of gastric body and antrum strips induced by acetylcholine (ACh), but not that induced by carbachol (CCh). Neostigmine also significantly enhanced the contraction of gastric body strips induced by ACh, but not that by CCh. In contrast, mosapride failed to enhance contractions induced by either ACh or CCh in gastric antrum strips. Acotiamide exerted mixed inhibition of AChE, and the percentage inhibition of acotiamide (100 µM) against AChE activity was markedly reduced after the reaction mixture was dialyzed. In contrast, itopride exerted noncompetitive inhibition on AChE activity. These results indicate that acotiamide enhances ACh-dependent contraction in gastric strips of guinea pigs via the inhibition of AChE activity, and that it exerts mixed and reversible inhibition of AChE derived from guinea pig stomach.

Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs.

UNLABELLED: BACKGROUND Acotiamide hydrochloride (acotiamide), a novel selective acetylcholinesterase (AChE) inhibitor, has proven significantly effective in treating functional dyspepsia (FD) in clinical trials, particularly in alleviating meal-related symptoms. In the present study, we examined the gastrointestinal prokinetic effects of acotiamide administered orally or intraduodenally in conscious dogs and investigated in vivo and ex vivo anti-AChE activity of acotiamide to clarify its mechanism of prokinetic action. METHODS: Gastrointestinal motility was measured in conscious dogs with chronically implanted force transducers. KEY RESULTS: Oral administration of acotiamide stimulated postprandial gastroduodenal and colonic motor activities. Measurement of gastrointestinal motility showed that acotiamide, like itopride and mosapride, enhanced gastric antral motility. Further, acotiamide markedly improved clonidine (an α(2) -adrenoceptor agonist)-induced hypomotility in a dog model of gastric motor dysfunction. The postprandial gastric antral motility enhanced by acotiamide was completely abolished on treatment with the muscarinic receptor antagonist atropine. Results of an in vivo experiment on anti-AChE activity showed clearly increased acetylcholine-induced gastric motility on intraduodenal administration of acotiamide, just as observed with the AChE inhibitor neostigmine. Further, in ex vivo experiment, intraduodenal administration of acotiamide significantly inhibited AChE activity in canine gastric antrum. CONCLUSIONS & INFERENCES: Our findings revealed that acotiamide administered through the alimentary tract exerts gastroprokinetic action via cholinergic pathways by inhibiting AChE activity. These results may also confirm the mechanism of action in clinical efficacy of acotiamide on FD.

Antiproteinuric effect of angiotensin-converting enzyme inhibitors and an angiotensin II receptor blocker in patients with lupus nephritis.

Although the effects of angiotensin II receptor blockers (ARBs) on non-diabetic glomerulonephritis have been reported, studies of their effects on collagen-vascular diseases, particularly lupus nephritis, are limited. In this retrospective, observational study, systemic lupus erythematosus (SLE) patients (n = 7) with lupus nephritis and uncontrolled proteinuria were treated with an angiotensin-converting enzyme inhibitor followed by the ARB losartan (25 - 50 mg/day). Urinary protein excretion and renal function were evaluated. After 12 months of losartan, mean urinary protein excretion decreased significantly by 84.8%. Mean systolic and diastolic blood pressures also decreased significantly during the 12 months of losartan treatment, although not in normotensive patients. Complement 4, total complement activity and anti-dsDNA antibody levels, which are indices of SLE activity, and serum creatinine levels, which is an index of renal function, showed no change in response to losartan treatment. A more extensive evaluation of the effects of ARBs in patients with lupus nephritis and poorly controlled proteinuria is required.

Spiking expression of mu-crystallin mRNA during treatment with methimazole in patients with graves' hyperthyroidism.

mu-Crystallin is an NADPH-dependent cytosolic T3-binding protein. A knockout study in mice showed that mu-crystallin has a physiological function as a reservoir of T3 in the cytoplasm in vivo. Patients with nonsyndromic deafness were reported to have point mutations in the mu-crystallin gene. The expression of mu-crystallin is regulated by multiple factors. The present study was performed to determine whether thyroid function is related to the expression of mu-crystallin mRNA in peripheral mononuclear cells. We examined 23 normal healthy male and female subjects and 15 patients with Graves' disease. mu-Crystallin protein expression was determined immunohistochemically in peripheral mononuclear cells. The expression of mu-crystallin mRNA was assessed by reverse transcription of total RNA from peripheral mononuclear cells followed by quantitative PCR. mu-Crystallin protein was detected in peripheral mononuclear cells. The mRNA expression was negatively correlated with age in normal female subjects. The values in female subjects were significantly higher than those in males. The values were positively correlated with serum TSH concentration. The values of the thyrotoxic patients with Graves' disease were lower than those in healthy subjects. A transient increase in mu-crystallin expression was observed within 14-42 days after the initial treatment with antithyroid medication. Thyroid hormone inversely relates to the expression of mu-crystallin mRNA in euthyroid mononuclear cells. Abrupt suppression of thyroid function leads to overexpression of mu-crystallin mRNA in thyrotoxic mononuclear cells. Thyroid hormone-regulated mu-crystallin expression may control thyroid hormone action via the intracytoplasmic T (3) capacity.

Clinical observations of postoperative delirium after surgery for oral carcinoma.

The aim of the present study was to clarify the clinical characteristics of postoperative delirium and to determine appropriate postoperative management for its prevention. The authors analysed 132 cases of primary surgery for oral carcinoma and observed 24 (18%) cases of postoperative delirium. Univariate analysis revealed that significant risk factors for postoperative delirium were older age, male gender, extensive surgery and morphine pain control. Logistic regression analysis showed that older age and male gender were significant risk factors for postoperative delirium, while patient-controlled analgesia with fentanyl was effective for prevention of postoperative delirium. There was a trend for postoperative delirium to be associated with extensive surgery. In those who had delirium, blood tests revealed that alkaline phosphatase, total protein, sodium, chlorine, red blood cell count, haemoglobin and haematocrit were significantly diminished after surgery. These results indicate that general condition is closely related to the onset of postoperative delirium, and suggest that appropriate postoperative management can reduce the incidence of this complication.

Treatment of a Gilbert's syndrome patient with irinotecan, leucovorin and 5-fluorouracil.

The patient was an elderly male who had radical surgery for sigmoid cancer in 2001. Owing to metastasis of his cancer to the left supraclavicular lymph nodes in 2002, the patient was admitted to our hospital for systemic chemotherapy. We started treatment with irinotecan, leucovorin, 5-fluorouracil (IFL). After administering 100 mg/m2 of irinotecan, 250 mg/m2 leucovorin and 600 mg/m2 5-fluorouracil to the patient on day 1, grade 3 leukopenia developed rapidly and grade 4 thrombocytopenia was observed on day 5. We excluded irinotecan from the medication and continued the administration of 5-fluorouracil and leucovorin, but his tumors had not been reduced sufficiently. Based on some examination results, we assumed that the patient had Gilbert's syndrome and that the severe side effects that occurred were due to prolongation of SN38 metabolism. We again administered irinotecan but at reduced dose (25 mg/m2). Four courses of this modified IFL were administered safely and the response was favorable.

Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients with Sjögren's syndrome.

The pathogenesis of Sjögren's syndrome (SS) is poorly understood. In this study we used an in-house mouse spleen cDNA microarray to analyse genes in spleens from MRL/lpr (an SS mouse model) mice. We have previously demonstrated that GRAP genes were up-regulated in salivary glands of the same mice. The microarray analysis showed that seven out of 2304 genes were highly expressed in spleens from the MRL/lpr mice, one of which was the GRAP gene. In other words, the GRAP gene is highly expressed in the salivary glands and spleen of MRL/lpr mice. We also carried out immunohistochemical studies. Mouse and human Grb-2-related adaptor protein (GRAP) antigens were expressed on ductal cells and infiltrating lymphocytes in salivary glands of MRL/lpr mice and SS patients, but only weakly in controls (MRL/+ mice and individuals with salivary cysts). These results suggest that the GRAP gene might have a role in the pathogenesis of SS.

A new tactile skin sensor for measuring skin hardness in patients with systemic sclerosis and autoimmune Raynaud's phenomenon.

We used a new tactile sensor to measure the elastic properties of skin in patients with systemic sclerosis or Raynaud's phenomenon. The sensor consists of a piezoelectric vibrator with vibration pickup to measure frequency changes when the sensor is placed on the skin. The mean frequency change at the skin surface of the proximol third phalanx in patients with systemic sclerosis was significantly lower than in age- and sex-matched controls. The results in systemic sclerosis patients were statistically correlated to the Modified Rodnan Skin Thickness Score. This technique was also used to measure the therapeutic efficacy of salpogrelate, a new specific serotonin receptor antagonist. A greater mean frequency change was seen after treatment. We conclude that this new tactile sensor is useful for quantitatively measuring skin sclerosis and may help determine the efficacy of therapeutic treatments.

Actual behaviour of N-butyl-2-cyanoacrylate (histoacryl) in a blood vessel: a model of the varix.

BACKGROUND AND STUDY AIMS: Though many gastric varices are treated endoscopically with n-butyl-2-cyanoacrylate, its behavior in varices is not known precisely. MATERIALS AND METHODS: We created a varix model. A volume of 0.7 ml or 1.4 ml of 71.4 % n-butyl-2-cyanoacrylate, a tissue adhesive, was injected into vinyl tubes of 0.4, 0.6, 0.9, and 1.2 cm in diameter, which were filled with still blood or flowing blood. The tissue adhesive was also injected into the inferior vena cava or femoral vein of dogs. RESULTS: N-butyl-2-cyanoacrylate was similarly polymerized in the vinyl tubes and the animal veins. A volume of 0.7 ml of the tissue adhesive could block all tubes up to 0.6 cm in diameter. A double quantity of the tissue adhesive could block tubes 0.9 and 1.2 cm in diameter, with flow velocities up to 10 cm/s and up to 5 cm/s, respectively. Some polymer masses were fragmented. CONCLUSIONS: One rapid shot of the tissue adhesive can block a vessel 0.6 cm or less in diameter with fast flow velocity, and a vessel up to 1.2 cm in diameter with slow flow velocity. Fast blood flows in a larger diameter vessel and slow injection of the tissue adhesive may result in fragmentation. This model of the varix was useful for assessing the effect of tissue adhesive used to treat gastric varices.

5-HT2A promoter polymorphism is not associated with anorexia nervosa in Japanese patients.

Genetic factors have been implicated in playing a significant role in susceptibility to anorexia nervosa (AN). Among many candidate genes for AN, an association with the A allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor has been reported. However, these findings are controversial and all patients studied to date have been Caucasian. This study was designed to determine whether this association is reproducible in Japanese subjects. This case-control study of a cohort of 75 female Japanese AN sufferers and 127 normal female control subjects revealed no significant association between the 5-HT2A promoter polymorphism and AN. Thus, at least for Japanese subjects, the A-allele of the -1438G/A polymorphism in the promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to AN.

Analysis of tumor necrosis factor-alpha gene promoter polymorphisms in anorexia nervosa.

Elevated plasma tumor necrosis factor-alpha (TNFalpha) levels and enhanced spontaneous TNFalpha release from peripheral blood mononuclear cells in patients with anorexia nervosa (AN) have been reported. TNFalpha activates the hypothalamic-pituitary-adrenal axis and reduces food intake, which is characteristic of eating disorders. Recently, three novel polymorphisms in the 5'-flanking region of the TNFalpha gene were reported at positions -1031 (T --> C substitution), -863 (C --> A) and -857 (C --> T). Differences in these alleles are reportedly related to altered TNFalpha-transcriptional promoter activity. Therefore, we performed a case-control association analysis to determine whether any of those three polymorphisms in the TNFalpha promoter region were involved in a predisposition to AN. The results of our analysis of a cohort of 79 female Japanese AN sufferers and 127 normal female control subjects provide no support for the hypothesis that -1031T/C, -863 C/A and -857C/T polymorphisms in the TNFalpha gene promoter region influence the susceptibility to AN.

Target preference of 15 quinolones against Staphylococcus aureus, based on antibacterial activities and target inhibition.

The antibacterial activities and target inhibition of 15 quinolones against grlA and gyrA mutant strains were studied. The strains were obtained from wild-type Staphylococcus aureus MS5935 by selection with norfloxacin and nadifloxacin, respectively. The antibacterial activities of most quinolones against both mutant strains were lower than those against the wild-type strain. The ratios of MICs for the gyrA mutant strain to those for the grlA mutant strain (MIC ratio) varied from 0.125 to 4. The ratios of 50% inhibitory concentrations (IC(50)s) of quinolones against topoisomerase IV to those against DNA gyrase (IC(50) ratios) also varied, from 0.177 to 5.52. A significant correlation between the MIC ratios and the IC(50) ratios was observed (r = 0.919; P < 0.001). These results suggest that the antibacterial activities of quinolones against the wild-type strain are involved not only in topoisomerase IV inhibition but also in DNA gyrase inhibition and that the target preference in the wild-type strain can be anticipated by the MIC ratios. Based on the MIC ratios, the quinolones were classified into three categories. Type I quinolones (norfloxacin, enoxacin, fleroxacin, ciprofloxacin, lomefloxacin, trovafloxacin, grepafloxacin, ofloxacin, and levofloxacin) had MIC ratios of <1, type II quinolones (sparfloxacin and nadifloxacin) had MIC ratios of >1, and type III quinolones (gatifloxacin, pazufloxacin, moxifloxacin, and clinafloxacin) had MIC ratios of 1. Type I and type II quinolones seem to prefer topoisomerase IV and DNA gyrase, respectively. Type III quinolones seem to target both enzymes at nearly the same level in bacterial cells (a phenomenon known as the dual-targeting property), and their IC(50) ratios were approximately 2.