Appropriate Preconception Corticosteroid-Free Remission Period in Pregnant Women With Ulcerative Colitis.

BACKGROUND: In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). METHODS: We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to <3 months, and non-CFREM). We also investigated disease activity during pregnancy and postpartum and adverse pregnancy outcomes in each group. RESULTS: During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to <3 months CFREM groups compared with that in the non-CFREM group (P < .001 and P = .0257, respectively). Postpartum, the rate of active disease was significantly lower in the ≥3 months CFREM group compared with that in the non-CFREM group (P = .0087). The preconception CFREM period of ≥3 months was an independent inhibitory factor for active disease during pregnancy and postpartum (adjusted odds ratio, 0.15; P = .0035; and adjusted odds ratio, 0.33; P = .027, respectively). Adverse pregnancy outcomes were less common in the >3 months CFREM group compared with those in the other groups, but this difference was not significant. CONCLUSIONS: A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

In women with ulcerative colitis, a preconception corticosteroid-free remission period for at least 3 months may be appropriate. This period could reduce disease activity during pregnancy and postpartum and reduce the incidence of adverse pregnancy outcomes.

Fluid-Blood Level and Hematoma Expansion in a Cerebral Amyloid Angiopathy-Associated Intracerebral Hematoma.

BACKGROUND Cerebral amyloid angiopathy (CAA) results from progressive deposition of amyloid-ß in the walls of cortical and leptomeningeal vessels, leading to CAA-associated intracerebral hemorrhage (ICH). Hematoma expansion is a common early complication of spontaneous ICH, and is a strong independent predictor of poor outcome. However, there are limited reports of hematoma expansion related to CAA-associated ICH. Herein, we describe a novel case of hematoma expansion with a fluid-blood level in the cystic cavity of CAA-associated ICH. CASE REPORT A 76-year-old male was initially diagnosed with probable CAA according to the modified Boston criteria, and presented with lobar ICH in the left frontal lobe 4 months later. Admission computed tomography scans showed an ICH including a high-density hematoma within a cystic cavity, revealing a clearly lower-density fluid component. Serial computed tomography scans showed no evidence of an expansion of the high-density clot, but obvious expansion of the fluid component containing a fluid-blood level. We recognized a bleeding site with no enhancement on preoperative magnetic resonance imaging. Left frontal craniotomy revealed a liquefied hematoma, which was removed by suction. We subsequently evacuated the blood clot extending into the left frontal sulcus, and confirmed and cauterized the bleeding site, leading to successful hemostasis. CONCLUSIONS We report a CAA-associated ICH case showing hematoma expansion with a fluid-blood level. Intraparenchymal fluid-blood level suggests extravasation of blood into pre-existing cystic cavities because of hematoma liquefaction. Thus, fluid-blood levels are an important finding of hematoma expansion in acute CAA-associated ICH, and early treatment should be considered.

Wound healing efficacy of a 660-nm diode laser in a rat incisional wound model.

This study aimed to elucidate the optimum usage parameters of low reactive-level laser therapy (LLLT) in a rat incisional wound model. In Sprague-Dawley rats, surgical wounds of 15-mm length were made in the dorsal thoracic region. They were divided into groups to receive 660-nm diode laser irradiation 24 h after surgery at an energy density of 0 (control), 1, 5, or 10 J/cm2. Tissue sections collected on postoperative day 3 were stained with hematoxylin-eosin and an antibody for ED1 to determine the number of macrophages around the wound. Samples collected on day 7 were stained with hematoxylin-eosin and observed via polarized light microscopy to measure the area occupied by collagen fibers around the wound; day 7 skin specimens were also subjected to mechanical testing to evaluate tensile strength. On postoperative day 3, the numbers of macrophages around the wound were significantly lower in the groups receiving 1 and 5 J/cm2 irradiation, compared to the control and 10 J/cm2 irradiation groups (p < 0.01). The area occupied by collagen fibers in day 7 was largest in 5 J/cm2 group, followed by 1 J/cm2 group, although this difference was not significant. The day 7 tensile test demonstrated significantly greater rupture strength in healing tissues from 1 and 5 J/cm2 irradiation groups, compared to the control group (p < 0.05). Thus, LLLT with a 660-nm diode laser with energy density of 1 and 5 J/cm2 enhanced wound healing in a rat incisional wound model. However, a higher radiation energy density yielded no significant enhancement.

A screening instrument to identify ulcerative colitis patients with the high possibility of current non-adherence to aminosalicylate medication based on the Health Belief Model: a cross-sectional study.

BACKGROUND: Non-adherence to aminosalicylates is observed among 30% to 45% of patients with ulcerative colitis and increases the risk of relapse. The Health Belief Model is a theoretical model that could offer a broader perspective to improve patients' self-medication adherence. This study aimed to develop a screening instrument based on the Health Belief Model to screen patients with ulcerative colitis who had a high possibility of current non-adherence to aminosalicylates. The study was also designed to allow examination of factors of non-adherence. METHODS: A multicenter, cross-sectional study was conducted in outpatients diagnosed with ulcerative colitis and prescribed aminosalicylates. Non-adherence was defined as taking less than 80% of the prescribed dose. We hypothesized that there was a significant relationship between current aminosalicylate non-adherence and five components of the HBM: beliefs about taking aminosalicylates, disease characteristics, medication characteristics, abdominal symptoms, and sociodemographic characteristics. A logistic regression model was applied and the coefficients converted to a numeric scores in order to develop a screening instrument which could reliably discriminate non-adherent and adherent subjects. RESULTS: Non-adherence was observed in 127 (29.6%) of the 429 enrolled subjects. Lower perceptions of belief in taking aminosalicylates, absence of visible bleeding, eight daily tablets or less taken, and no concomitant use of thiopurines were related to non-adherence. We then developed a screening instrument comprising 22 items. When the cut-off point was set at 60, the instrument showed 85.0% sensitivity and 69.2% specificity with an area under the curve of 0.84 (95% confidence interval = 0.79-0.91). CONCLUSIONS: The instrument appeared to be reliable for identifying patients with a high possibility of current non-adherence to aminosalicylates. Further, the instrument may provide useful information for detecting patients with a high possibility of current non-adherence and for assessing factors of non-adherence. On the other hand, we need to evaluate disease activity more strictly and examine whether it is included in the screening instrument in the future.

Structural defects and positronium formation in 40 keV B(+)-implanted polymethylmethacrylate.

Slow positron beam and optical absorption measurements are carried out to study structural defects and positronium formation in 40 keV B(+)-implanted polymethylmethacrylate (B:PMMA) with ion doses from 6.25 × 10(14) to 5.0 × 10(16) ions/cm(2). Detailed depth-selective information on defects in implanted samples was obtained by measuring of Doppler broadening of positron annihilation γ rays as a function of incident positron energy and these experimental results were compared with SRIM (stopping and range of ions in matter) simulation results. Two general processes, appearance of free radicals at lower ion doses (<10(16) ions/cm(2)) and carbonization at higher ion doses (>10(16) ions/cm(2)), are considered from the Doppler S-E and W-E dependences in the framework of the concept of defects formation during radiation damage of polymer structure. Probabilities of ortho-positronium (o-Ps) formation are analyzed using S-W plot and slow positron annihilation lifetime measurements. Dose dependence of o-Ps lifetime τ3 and intensity I3 at the incident positron energy of 2.15 keV correlates well with the dose dependence of S-parameter and seems to account for the existence of the expected two processes, i.e., scission of polymer chains and appearance of free radicals preceding the aggregation of the clusters resulting in the formation of network of conjugated bonds at lower ion doses and carbonization at higher ion doses. The increase of optical absorption observed with increasing ion implantation dose also suggests a formation of carbonaceous phase in the ion-irradiated PMMA.

A murmur-free giant myxoma discovered incidentally on abdominal ultrasonography.

Patients with myxoma normally present with cardiovascular symptoms due to mitral valve obstruction caused by the tumor. However, some cases are difficult to diagnose because the findings of auscultation are normal and there are no cardiovascular symptoms. A 62-year-old man presented at a nearby clinic with a fever. No cardiac murmurs were heard on a physical examination. Abdominal ultrasonography was conducted to evaluate the origin of the fever, and a giant left atrial myxoma was discovered incidentally. Although many myxoma cases are found on transthoracic echocardiography, we herein describe a case of a giant left atrial myxoma incidentally discovered on abdominal ultrasonography.

Establishment of five canine lymphoma cell lines and tumor formation in a xenotransplantation model.

Five novel, canine lymphoma cell lines (Ema, CLC, CLK, Nody-1 and UL-1) were established from dogs suffering from lymphoma and characterized in vitro and in vivo. All cell lines, except CLC, were characterized with T-cell phenotypes, by flow cytometric analysis and polymerase chain reaction for antigen receptor rearrangement. Cell proliferation rates and transcriptional levels of MYC, PTEN, KIT and FLT3 varied between each cell line. Intraperitoneal xenotransplantation of Ema, CLC, Nody-1 and UL-1 lymphoma cell lines into NOD/SCID mice induced ascites, intraperitoneal tumors and severe infiltration of lymphoma cells into the pancreas and mesentery. Establishment of novel canine lymphoma cell lines with different characteristics is critical for elucidating the pathophysiology of canine lymphoma and improving current therapies.

Anti-adhesive property of P-selectin glycoprotein ligand-1 (PSGL-1) due to steric hindrance effect.

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesive molecule that is known to be a ligand for P-selectin. An anti-adhesive property of PSGL-1 has not been previously reported. In this study, we show that PSGL-1 expression is anti-adhesive for adherent cells and we have elucidated the underlying mechanism. Overexpression of PSGL-1 induced cell rounding and floating in HEK293T cells. Similar phenomena were demonstrated in other adherent cell lines with overexpression of PSGL-1. PSGL-1 overexpression inhibits access of antibodies to cell surface molecules such as integrins, HLA and CD25. Cells transfected with PSGL-1 deletion mutants that lack a large part of the extracellular domain and chimeric construct expressing extracellular CD86 and intracellular PSGL-1 only showed rounded morphology, but there are no floating cells. These results indicated that PSGL-1 causes steric hindrance due to the extended structure of its extracellular domain that is highly O-glycosylated, but intracellular domain also has some effect on cell rounding. This study implies that PSGL-1 has Janus-faced functions, being both adhesive and anti-adhesive.

Tailoring the chain packing in ultrathin polyelectrolyte films formed by sequential adsorption: nanoscale probing by positron annihilation spectroscopy.

Depth profiling experiments by positron annihilation spectroscopy have been used to investigate the free volume element size and concentration in films assembled using the layer-by-layer (LbL) adsorption method. Films prepared from strong polyelectrolytes, weak polyelectrolytes, hydrogen-bonding polymers, and blended polyelectrolyte multilayers have different chain packing that is reflected in the free volume characteristics. The influence of various parameters on free volume, such as number of bilayers, salt concentration, solution pH, and molecular weight, has been systematically studied. The free volume cavity diameters vary from 4 to 6 Å, and the free volume concentrations vary from (1.1-4.3) × 10(20) cm(-3), depending on the choice of assembly polymers and conditions. Films assembled from strong polyelectrolytes have fewer free volume cavities with a larger average size than films prepared from weak polyelectrolytes. Blending the weak polyanion poly(acrylic acid), PAA, with the strong polyanion poly(styrene sulfonate), PSS, to layer alternately with the polycation poly(allyamine hydrochloride), PAH, is shown to be a viable method to achieve intermediate free volume characteristics in these LbL films. An increase in salt concentration of the adsorption solutions for films prepared from strong polyelectrolytes makes these films tend toward weaker polyelectrolyte free volume characteristics. Hydrogen-bonded layered films show larger free volume element size and concentration than do their electrostatically bonded counterparts, while reducing the molecular weight of these hydrogen-bonded polymers results in slightly reduced free volume size and concentration. A study of the effect of solution pH on films prepared from weak polyelectrolytes shows that when both polyelectrolytes are substantially charged in solution (assembly pH = 7.5), the chains pack similarly to strong polyelectrolytes (i.e., lower free volume concentration), but with smaller average cavity sizes. These results give, for the first time, a clear indication of how the free volume profile develops in LbL thin films, offering numerous methods to tailor the Ångström-scale free volume properties by judicious selection of the assembly polymers and conditions. These findings can be potentially exploited to tailor the properties of thin polymer films for applications spanning membranes, sensing, and drug delivery.

Pore size determination of TEMPO-oxidized cellulose nanofibril films by positron annihilation lifetime spectroscopy.

Wood cellulose nanofibril films with sodium carboxylate groups prepared from a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidized pulp exhibited an extremely low oxygen permeability of 0.0008 mL µm m(-2) day(-1) kPa(-1) at 0% relative humidity (RH). Positron annihilation lifetime spectroscopy (PALS) was used to determine the pore sizes in wood and tunicate TEMPO-oxidized cellulose nanofibril (TOCN-COONa) films in a vacuum (i.e., at 0% RH). PALS analysis revealed that the pore size of the wood TOCN-COONa films remained nearly at 0.47 nm from the film surface to the interior of the film. This is probably the cause of this high oxygen-barrier properties at 0% RH. The crystalline structure of TOCN-COONa also contributes to the high oxygen-barrier properties of the wood TOCN-COONa films. However, the oxygen permeability of the wood TOCN-COONa films increased to 0.17 mL µm m(-2) day(-1) kPa(-1) at 50% RH, which is one of the shortcomings of hydrophilic TOCN-COONa films.

Characterization of monoclonal antibodies against canine P-selectin glycoprotein ligand-1 (PSGL-1).

Thirteen different monoclonal antibodies against canine P-selectin glycoprotein ligand-1 (cPSGL-1) were obtained by immunization of rats with cells of a canine lymphoma cell line (Ema). O-sialoglycoprotein endopeptidase treatment of Ema cells showed that all of these antibodies recognized O-glycosylated peptides of canine PSGL-1. Experiments using deletion or point mutants of cPSGL-1 indicated that these antibodies could be categorized into several groups based on their cPSGL-1 recognition characteristics. These anti-cPSGL-1 monoclonal antibodies will be useful for analysis of the canine P-selectin and PSGL-1 system.

An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment.

OBJECTIVES: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.

Crossreactivity of antibodies to canine CD25 and Foxp3 and identification of canine CD4+CD25 +Foxp3+ cells in canine peripheral blood.

The importance of CD4(+)CD25(+)Foxp3 (+) regulatory T cells (Treg cells) in immune response is increasingly being recognized. However, to date, only a few studies on these cells have been conducted in canine species, partly because of the unavailability of appropriate antibodies to detect this cell population. In this study, the crossreactivities of anti-human CD25 antibody (clone ACT-1) and anti-mouse Foxp3 antibody (clone FJK16s) to canine CD25 and Foxp3, respectively, were confirmed using cell lines overexpressing either of these genes. By using these antibodies, we determined if CD4(+), CD25(+), or Foxp3(+) cells were present in unstimulated canine peripheral blood mononuclear cells (PBMCs) and in concanavalin A (ConA)-stimulated PBMCs. CD25(+) cells were not detected in unstimulated canine PBMCs, unlike in human or mouse PBMCs. ConA stimulation of canine PBMCs induced Foxp3 and CD25 expression in CD4(+) and CD4(-) cells. These data indicate that the activation of canine lymphocytes might induce the production of adaptive Treg cells, as observed in humans.

Porogen approach for the fabrication of plasma-polymerized nanoporous polysiloxane films.

Nanoporous polysiloxane films were fabricated by plasma polymerization of hexamethyldisiloxane mixed with cyclohexane under different conditions. The pores were generated through the elimination of carbonaceous aggregates (porogen) by annealing at 600 degrees C. Results of spectroscopic ellipsometry, Fourier transform infrared spectroscopy, and positron annihilation lifetime spectroscopy suggest that not only film porosity but also average pore size depends on the amount of the decomposable porogen. The pore size was controllable in a range between 0.6 and 1.0 nm in radius by proper selection of the substrate temperature and precursor composition.

Mechanism of enhanced positronium formation in low-temperature polymers.

An enhanced positronium (Ps) formation in low-temperature polymers has been widely observed. The additional positronium formation is due to shallow trapped electrons in them. Positron annihilation lifetime spectroscopy was applied to investigate the Ps formation in a series of polymers, such as low-density polyethylene, ethylene-methyl methacrylate copolymers with various methyl methacrylate contents, and pure poly(methyl methacrylate) at low temperature. An analysis of the experimental data based on simple kinetic equations enables one to understand the Ps formation mechanism in polymers during low-temperature positron annihilation experiments as functions of the temperature and elapsed time. Good fittings of the experimental data were obtained. The fitting parameters seemed to show clear physical meanings.

Neurokinins modulate hyperventilation-induced bronchoconstriction in canine peripheral airways.

This study was designed to test the hypotheses that (1) neurokinin (NK) receptor activity modulates hyperventilation-induced bronchoconstriction (HIB) in canine peripheral airways and (2) NK receptor activity is stimulated via hyperventilation-induced eicosanoid production and release. A bronchoscope was used in anesthetized dogs to record peripheral airway resistance (Rp); to test airway reactivity to NK A (NKA), substance P, and hypertonic saline; and to examine HIB before and after combined treatment with NK-1 (CP 99,994) and NK-2 (SR 48,968) receptor antagonists. Bronchoalveolar lavage fluid cells, prostaglandin D2, and cysteinyl leukotrienes from hyperventilated airways pretreated with either vehicle or NK antagonists were also measured. Pretreatment with NK-1 and NK-2 antagonists significantly attenuated HIB and the response to substance P, virtually abolished the response to NKA, and had little effect on the response to HS. Blockade of NK-1 and NK-2 receptors did not affect either the cell profiles or the mediator concentrations recovered in bronchoalveolar lavage fluid after hyperventilation. We conclude that NKs modulate the development of HIB and appear to do so via hyperventilation-induced eicosanoid production and release.

[Risk factors in development of sleep apnea syndrome--a large population study using a simple monitoring system].

We studied the risk factors in the development of sleep apnea syndrome (SAS) in 779 patients (705 males and 74 females) using Apnomonitor R. The apnea index (AI) significantly correlated with the body mass index (BMI), and was higher in obese patients (BMI > or = 25 kg/m2) than in non-obese patients. The prevalence of SAS increased with patient age. Obesity was less common in older than in younger patients. The AI was significantly higher in smokers than in non-smokers, as was the prevalence of SAS. The AI and the prevalence of SAS were higher in smokers than in non-smokers in both obese and non-obese patients. The AI was significantly higher in males than in females, and so was the prevalence of SAS. The AI and the prevalence of SAS were always higher in male obese patients, non-obese patients, smokers, and non-smokers than in female patients in the same categories. These results suggest that obesity, age, smoking, and gender were independent risk factors in the development of SAS.

[Relationship between location of stress erosive gastritis and brain damage in resuscitated patients].

Patients after resuscitation from cardiopulmonary arrest often show stress erosive gastritis. This study investigated the relationship between the location of gastric mucosal injury and the degree of brain damage. Forty-five resuscitated patients with gastrointestinal bleeding complications were enrolled and were examined by esophagogastric fiberscope after 72 hours of hospitalization. Their brainstem and cerebral functions were evaluated brainstem auditory evoked potential (BAEP) and electrical encephalogram (EEG), respectively. Thirty patients showed complications with acute gastric lesions. Ten patients had gastric mucosal injury in the antrum and they all showed a good response for BAEP (I, III and V waves were positive). In contrast, patients without antral gastric mucosal lesions showed poor response for ABR (defect of III and V waves) and EGG (Hockerday Grade III or IV). These results indicate that fair brainstem function is necessary for stress erosive gastritis in gastric antrum.

Heparin inhibits hyperventilation-induced late-phase hyperreactivity in dogs.

Inhalation of heparin attenuates hyperventilation-induced bronchoconstriction in humans and dogs. The purpose of this study was to determine whether heparin inhibits the late-phase response to hyperventilation, which is characterized by increased peripheral airway resistance (RP), eicosanoid mediator production, neutrophilic/ eosinophilic inflammation, and airway hyperreactivity (AHR) at 5 h after dry air challenge (DAC). Fiberoptic bronchoscopy was used to record RP and airway reactivity (DeltaRP) to aerosol and intravenous histamine before and 5 h after DAC. Bronchoalveolar lavage fluid (BALF) cells and eicosanoid mediators were also measured approximately 5 h after DAC. DAC of vehicle-treated bronchi resulted in late-phase airway obstruction (approximately 120% increase over baseline RP), inflammation, increased BALF concentrations of leukotriene (LT) C(4), LTD(4), and LTE(4) and prostaglandin (PG)D(2), and AHR. Pretreatment with aerosolized heparin attenuated late-phase airway obstruction by approximately 50%, inhibited eosinophil infiltration, reduced BALF concentrations of LTC(4), LTD(4), and LTE(4) and PGD(2), and abolished AHR. We conclude that heparin inhibits hyperventilation-induced late-phase changes in peripheral airway function, and does so in part via the inhibition of eosinophil migration and eicosanoid mediator production and release.