An indirect comparison of long-term efficacy of every-2-week dosing vs. recommended dosing of ixekizumab in patients who had static Physician's Global Assessment > 1 at week 12.

BACKGROUND: Long-term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate-to-severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. METHODS: Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA-P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER-1, UNCOVER-2 and UNCOVER-3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. RESULTS: In the IXORA-P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA-P study. CONCLUSIONS: Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA-P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate-to-severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160-mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance. Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks. The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12.

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis.

BACKGROUND: Mutations in FLG, which encodes profilaggrin, cause ichthyosis vulgaris (IV) and are an important predisposing factor for atopic dermatitis (AD). IV shows autosomal hemidominant (semidominant) inheritance, and patients with bi-allelic FLG mutations tend to have severe IV phenotypes. However, the effect of bi-allelic FLG mutations on AD incidence and severity remains a subject of controversy. OBJECTIVE: In this study, we studied individuals with bi-allelic null FLG mutations to elucidate the effect of bi-allelic FLG mutations on AD incidence and severity. METHODS: Six individuals with bi-allelic FLG null mutations from three families of IV/AD were investigated. We report the detailed clinical features of the individuals. The phenotype was confirmed by the clinical examinations and the severity of IV and AD was scored using ichthyosis score and Eczema Area and Severity Index (EASI). RESULT: It was found that five of the six patients had severe IV, and the remaining patient showed moderate IV. Two of the six had moderate AD and three of the six had mild AD. The remaining patient had no AD. CONCLUSION: Our results suggest that individuals with bi-allelic FLG mutations do not always have severe AD and confirm that not all individuals with bi-allelic FLG mutations have AD.

Comparison of Volumetric and Diametric Analysis in Endovascular Repair of Descending Thoracic Aortic Aneurysm.

OBJECTIVES: The aim was to evaluate computed tomography angiography (CTA) volumetric and diametric analysis after endovascular repair of descending thoracic aortic aneurysms (DTAAs) and its correlation with and applicability for clinical follow up. METHODS: Fifty-four consecutive endovascular repairs for DTAA were retrospectively evaluated from 2008 to 2014. All patients underwent pre-operative CTA and at least one post-operative CTA at 6 months. Fifty-four pre-operative and 137 post-operative CTAs were evaluated (using the Ziosoft 2 software) to analyze the aneurysm and thrombus volume, the maximum aneurysm diameter, and their changes at the last follow up CTA (mean 30.5 months; range 6.5-66.4 months). A statistical analysis was performed to assess the correlation between diameter and volume changes, as well as association with endoleaks. The cut off point to predict endoleaks was determined using a receiver operating characteristic (ROC) curve. The predictive accuracy of volume change versus diameter change for Type I endoleak was analyzed. RESULTS: The mean pre-operative aneurysm diameter, aneurysm volume, and thrombus volume were 56.7 ± 11.7 mm, 145.8 ± 120.0 mL, and 48.8 ± 54.8 mL, respectively. Within the observational period, a mean decrease of -27.9 ± 30.5% in the aortic volume and -15.9 ± 15.4% in diameter was observed. Correlation between aneurysm diameter and volume changes was good (r = 0.854). Volume and diameter changes were significantly different between groups with and without endoleaks (volume change 16.9 ± 38.8% vs. -35.6 ± 23.1%, p < .001; diameter change 8.0 ± 12.1% vs. -18.8 ± 14.3%, p < .001). A pre-operative thrombus volume percentage of <11.3% and increase in aneurysm volume +11.6% were predictive factors for Type II and Type I endoleak, respectively. The accuracy of a >10% volume increase in predicting a Type I endoleak was higher (accuracy 96.3%, sensitivity 75%, and specificity 98%) than a >5 mm diameter increase (accuracy 92.6%, sensitivity 25%, and specificity 98%). CONCLUSIONS: CT volumetric analysis is a more reliable modality for predicting endoleaks after endovascular repair for DTAA than diameter analysis.

Cathepsin B activity has a crucial role in the developmental competence of bovine cumulus-oocyte complexes exposed to heat shock during in vitro maturation.

Cathepsin B was found to be correlated inversely with the quality of bovine oocytes and embryos. The aims of this study were to evaluate i) the relationship between heat shock during in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs) and cathepsin B activity in relation to apoptosis and ii) the effect of supplementation of cathepsin B inhibitor (E-64) during IVM of heat-shocked COCs on embryonic development. After IVM at 38.5 °C for 22 h (control group) or at 38.5 °C for 5 h followed by 41 °C for 17 h (heat shock group) either with or without 1 µM E-64, activities and protein expression of cathepsin B and caspase 3 were evaluated as well as TUNEL staining. After IVF, developmental rate, total cell number, and the percentage of apoptotic cells in blastocysts were evaluated on day 8 (day 0, IVF day). Heat-shocked IVM COCs showed significantly high activities and expressions of both cathepsin B, and caspase 3 accompanied by a significant increase in number of TUNEL-positive cells. Addition of E-64 significantly decreased the activities of cathepsin B and caspase 3, and TUNEL-positive cells in heat-shocked IVM COCs. Moreover, addition of 1 µM E-64 during IVM under heat shock conditions significantly improved both developmental competence and quality of the produced embryos. These results indicate that heat shock induction of cathepsin B is associated with apoptosis of COCs, and inhibition of cathepsin B activity can improve the developmental competence of heat-shocked COCs during IVM.

Heat-killed bacillus Calmette-Guérin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells.

BACKGROUND: Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette-Guérin (BCG) has been used for preventing tuberculosis, and is regarded as a strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in Mycobacterium species that induces Th1 cytokine production. OBJECTIVES: We investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and Mycobacterium kansasii Ag85B in an AD mouse model. METHODS: For the AD model, keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used. The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels were analysed. Inducible Foxp3+ regulatory T cells (iTreg), IL-10-producing T cells (Tr1), and interferon (IFN)-γ/IL-4/IL-17-producing T cells were evaluated in the spleen. RESULTS: Saline-treated mice and hkBCG monotherapy mice spontaneously developed severe dermatitis. However, combined therapy with hkBCG and Ag85B significantly suppressed the development of skin lesions and mast cell infiltrations. Elevations of the serum IgE and IL-18 levels were significantly suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal number of iTreg in the spleen, and decreased number of both IL-4- and IL-17-producing CD4+ T cells. The effect of Ag85B monotherapy was limited. CONCLUSIONS: Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing regulatory T cells, suggesting that this vaccination is a potent and novel therapeutic strategy for AD.

Serum adiponectin and leptin levels are useful markers for prostate cancer screening after adjustments for age, obesity-related factors, and prostate volume.

AIM: Adiponectin and leptin, polypeptide hormones produced by adipocytes, have recently been reported to be associated with prostate cancer risk, though, the relationship remains poorly understood. We examined the association of adiponectin and leptin levels in serum with prostate cancer risk after adjustments for age, obesity-related factors, and prostate cancer risk. METHODS: Fifty-four prostate cancer patients and 70 control subjects provided blood sampled between 2008 and 2009. Using those, we determined serum adiponectin and leptin levels, and evaluated their relationships with prostate cancer risk after adjustments for age, obesity-related factors (body weight, body mass index, waist circumference), and prostate volume. Adipokine densities were calculated by dividing serum level with prostate volume. RESULTS: There were no differences for median serum adiponectin and leptin levels between the prostate cancer and benign control groups (P=0.22 and 0.78, respectively). Patients with levels of both adipokines in the highest quartile after adjustment for age had significantly higher risks of prostate cancer (adiponectin: odds ratio [OR] 2.79, P=0.014; leptin: OR 2.72, P=0.027). Patients with an adiponectin level greater than the median after adjustment for body weight also had a significantly elevated risk of prostate cancer (OR 2.22, P=0.031), whereas, those with a leptin level significantly greater than the median had a significantly lower risk (OR 0.46, P=0.027). Furthermore, median adiponectin density was significantly higher in the prostate cancer group than the benign group (P=0.0033). CONCLUSION: Serum adiponectin and leptin levels are useful markers for prostate cancer risk after adjustments for age, obesity-related factors, and prostate volume.

Marked anti-tumour activity of the combination of YM155, a novel survivin suppressant, and platinum-based drugs.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein family, is an attractive target for cancer therapy. We have now investigated the effects of the combination of YM155, a novel small-molecule inhibitor of survivin expression, and platinum compounds (cisplatin and carboplatin) on human non-small cell lung cancer (NSCLC) cell lines. METHODS: The anti-cancer efficacy of YM155 in combination with platinum compounds was evaluated on the basis of cell death and progression of tumour xenografts. Platinum compound-induced DNA damage was evaluated by immunofluorescence analysis of histone gamma-H2AX. RESULTS: Immunofluorescence analysis of histone gamma-H2AX showed that YM155 delayed the repair of double-strand breaks induced in nuclear DNA by platinum compounds. The combination of YM155 and platinum compounds also induced synergistic increases both in the number of apoptotic cells and in the activity of caspase-3. Finally, combination therapy with YM155 and platinum compounds delayed the growth of NSCLC tumour xenografts in nude mice to an extent greater than that apparent with either treatment modality alone. CONCLUSION: These results suggest that YM155 sensitises tumour cells to platinum compounds both in vitro and in vivo, and that this effect is likely attributable to the inhibition of DNA repair and consequent enhancement of apoptosis.

Intracellular cathepsin B activity is inversely correlated with the quality and developmental competence of bovine preimplantation embryos.

Recently, the activity of cathepsins B was found to be correlated inversely with the developmental competence of bovine oocytes. In this study, we investigated (1) the role of intracellular cathepsin B expression and developmental competence as well as the quality of bovine preimplantation embryos, and (2) the effect of cathepsin B inhibitor (E-64) during in vitro culture (IVC) on the development and quality of bovine embryos. After in vitro fertilization (IVF) followed by IVC for 7 days, good and poor quality embryos classified by morphology and developmental rate on days 2, 4, and 7 were assessed for cathepsin B expression and activity. To investigate the effect of cathepsin B inhibition on embryonic development, putative zygotes were cultured with or without E-64, followed by evaluation of cleavage and blastocyst rates on days 2 and 7, respectively. Embryonic quality was evaluated by both TUNEL staining and total cell number in day-7 blastocysts. In each developmental stage, cathepsin B expression and activity were significantly higher in poor quality embryos than good quality ones. Moreover, addition of E-64 during IVC significantly increased both the blastocyst rate and the total cell number. TUNEL staining revealed that inhibition of cathepsin B significantly decreased the number of apoptotic nuclei in day-7 blastocysts. These results indicate that cathepsin B activity can be useful as a marker for inferior quality embryos. Moreover, inhibition of cathepsin B greatly improves the developmental competence of preimplantation embryos and increases the number of good quality embryos.

Cathepsin B activity is related to the quality of bovine cumulus oocyte complexes and its inhibition can improve their developmental competence.

Recently, the quantity of cathepsin transcripts in cumulus cells was found to be associated with low-developmental competence of bovine oocytes. In the present study, we investigated (1) the relation between cathepsin B activity and the quality of in vitro-matured cumulus-oocyte complexes (IVM COCs) and denuded oocytes and (2) the effect of a cathepsin B inhibitor (E-64) on embryo development and quality. The activity of cathepsin B was evaluated in IVM COCs and denuded oocytes. After maturation of COCs with or without E-64, followed by in vitro fertilization, zygotes were cultured for 8 days. Cleavage and blastocyst rates were evaluated on days 2 and 8, respectively. Quality of embryos was evaluated by differential staining of day 8 blastocysts. TUNEL staining was conducted on IVM COCs and blastocysts. Cathepsin B activity was clearly detected in the low-quality oocytes, and in the cumulus cells of both high- and low-quality oocytes. This latter activity was diminished by addition of E-64. The presence of E-64 during IVM also significantly increased both the blastocyst rate and the total cell number, and improved blastocyst quality associated with a significant increase of trophoectoderm cells. TUNEL staining revealed that inhibition of cathepsin B significantly decreased the number of apoptotic nuclei in both the cumulus cell layer of matured oocytes and blastocysts. These results indicate that cathepsin B activity can be a useful marker of oocyte quality. Furthermore, inhibition of cathepsin B greatly improves the developmental competence of bovine oocytes and increases the number of high-quality embryos.

1,24-Dihydroxyvitamin D3 (tacalcitol) prevents skin T-cell infiltration.

BACKGROUND: 1,24-Dihydroxyvitamin D3 (tacalcitol), a vitamin D(3) compound, has been used to treat T cell-mediated inflammatory skin diseases such as psoriasis, prurigo and vitiligo. The best-known mechanism of action of this compound is inhibition of the abnormal proliferation of keratinocytes and subsequent maturation; however, its effects on skin T-cell recruitment have not yet been evaluated. Cutaneous lymphocyte-associated antigen (CLA), a surface glycoprotein expressed on T cells, plays a critical role in skin T-cell infiltration. We recently reported that 1,25-dihydroxyvitamin D3 inhibits skin infiltration of CD4+ T cells by suppressing CLA expression on T cells. OBJECTIVES: In this study, we investigated the effect of tacalcitol on CLA epitope decoration and on the levels of gut or lymph node homing receptor expression in human T cells. METHODS: We cultured human T cells with tacalcitol and analysed the effect on CLA expression and skin-homing ability, and evaluated glycosyltransferase mRNAs. We also performed an in vivo study using an antigen-dependent delayed-type hypersensitivity (DTH) mouse model and investigated the effect of tacalcitol on skin-infiltrating CD4+ T cells. RESULTS: Tacalcitol downregulated the expression of CLA and, in parallel, the E- and P-selectin ligand function; however, it exerted no effect on other homing receptors. Subcutaneously and intraperitoneally administered tacalcitol downregulated skin infiltration of effector CD4+ T cells in an in vivo DTH mouse model. CONCLUSIONS: These findings suggest that tacalcitol reduces skin inflammation by partially downregulating CLA expression levels.

Large scale replication analysis of loci associated with lipid concentrations in a Japanese population.

BACKGROUND: Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken. METHODS: To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals. RESULTS: Multiple linear regression analyses showed that the rs3812316 in MLXIPL was strongly associated with triglyceride concentrations (p approximately 3.0x10(-11), 7.1 mg/dl decrease per minor C allele) and that rs599839 in CELSR2/PSRC1/SORT1 was strongly associated with LDL cholesterol concentrations (p approximately 3.1x10(-11), 4.7 mg/dl decrease per minor G allele) in the Japanese population. SNPs near ANGPTL3, TRIB1 and GALNT2 showed evidence for associations with triglyceride concentrations (3.6x10(-6)

[Needle tract implantation of hepatocellular carcinoma after sonographically guided percutaneous needle biopsy].

We reported a case of hepatocellular carcinoma (HCC) with needle tract implantation of the right thoracic wall, which were strongly suspected to have been caused by percutaneous needle biopsy performed at the former hospital to diagnose HCC in September 2001. He visited our hospital at his age of 68 and underwent transcatheter arterial embolization in February 2002. In November 2007, a right 9th intercostal tumor measuring 20 x 15 mm was found on his computed tomography (CT) scan. He underwent resection of the right thoracic wall tumor in January 2008. Pathological diagnosis of the tumor was well differentiated HCC. Twenty one months after surgery, he remains alive without recurrence.

[Emergency operation and hypothermic therapy for Stanford type A acute aortic dissection in the state of coma].

We report of a 77-year-old woman who was admitted to our hospital in coma by emergency. A computed tomography scan revealed acute aortic dissection (Stanford type A). We established selective antegrade cerebral perfusion within 3 hours of the onset and then performed ascending aortic replacement. In the state of hypothermia (35 degrees C), the patient was weaned from cardiopulmonary bypass. The patient was kept hypothermic until the operation was completed. We kept mild hypothermia (34.5 degrees C) in intensive care unit (ICU) for 40 hours. The patient was extubated at 94 hours after the operation. The patient was discharged from the hospital on foot on postoperative day 21.

IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic disease with a Th2-type-cytokine dominant profile. Several cytokines and related peptides have been used for the treatment of AD but they were ineffective because of their limited biological half-life. We have recently developed a highly efficient mouse dominant negative interleukin (IL)-4/IL-13 antagonist (IL-4DM), which blocks both IL-4 and IL-13 signal transductions. OBJECTIVE: To examine the effects of IL-4DM in vivo in an AD model induced by the repeated exhibition of oxazolone (OX). METHODS: Plasmid DNA was injected intraperitoneally to cause an experimental AD-like dermatitis. The effect was evaluated by ear thickness, histological findings, and mast cells counts in the inflamed skin. The plasma IgE and histamine levels were measured. Cytokine production in skin and splenocytes were also analysed. RESULTS: Mice treated with control plasmid developed marked dermatitis with mast cells and eosinophil infiltration, and had increased plasma IgE and histamine levels with a Th2 type splenocyte cytokine profile. Treatment with mouse IL-4 DNA augmented the ear swelling and thickness with an increased dermal eosinophil count, plasma histamine level, and production of splenocyte IL-4. However, IL-4DM treatment successfully controlled the dermatitis, decreased the mast cell and eosinophil count, and suppressed plasma IgE and histamine levels. Splenocytes produced an increased level of IFN-gamma. CONCLUSION: These data showed that the simultaneous suppression of IL-4/IL-13 signals successfully controlled Th2-type chronic dermatitis. IL-4DM DNA treatment is a potent therapy for AD and related diseases.

Amiodarone does not affect brain injury in a rat model of transient forebrain ischemia.

OBJECTIVES: Although amiodarone may cause neurotoxicity that can affect patient outcomes when used during cardiopulmonary resuscitation (CPR), it has been commonly prescribed during CPR. This study investigated the possible neurotoxic effects of amiodarone in a rat model of transient forebrain ischemia. DESIGN: A prospective laboratory animal study was carried out. SETTING: Animal laboratory. MATERIALS: Male Sprague-Dawley rats. INTERVENTION: Eight minutes of forebrain ischemia was induced in rats by bilateral carotid occlusion and hypotension (mean arterial pressure=35mmHg) under isoflurane (1.5%) anesthesia. Amiodarone (0, 50, 100 and 150mg/kg) with saline was injected intraperitoneally 10min after ischemia. Rats given 0mg/kg of amiodarone were used as saline-treated controls. Sham operated rats received no treatment. VARIABLES OF INTEREST: Animals were evaluated neurologically on postoperative days 4-7, and histologically after a one-week recovery period. RESULTS: The greatest improvement in water maze test performance corresponded to the sham operated group (p=0.015 vs. saline-treated controls). No differences in performance were seen in amiodarone-treated rats compared with saline-treated controls. In the control group, 45% of the CA1 hippocampal neurons survived, compared with 78% in the sham operated group (p=0.009). Neuron survival after ischemia in the amiodarone treatment groups (50, 100 and 150mg/kg) (58%, 40% and 36%, respectively) and in the control rats did not differ significantly. CONCLUSIONS: The administration of amiodarone immediately after transient forebrain ischemia did not worsen spatial cognitive function or neuronal survival in the hippocampal CA1 region in rats. The current results must be applied with caution in humans. However, they indicate that the potential neurotoxicity induced by amiodarone during resuscitation after cardiac arrest may be negligible.

The influence of temperature during water-quench rapid heat treatment on the microstructure, mechanical properties and biocompatibility of Ti6Al4V ELI alloy.

This study investigates the influence of a rapid heat treatment followed by water-quenching on the mechanical properties of Ti6Al4V ELI alloy to improve its strength for use in implants. Prior to the experiment, a dilatometry test was performed to understand the progressive α-to ß-phase transformation taking place during heating. The results were then used to carry out heat treatments. Microstructure was analysed using SEM, EBSD, EDX and XRD techniques. Vickers micro-hardness, tensile and high cycle rotating bending tests were used to analyse the influence of the $\alpha'$-phase fraction on the strength of the studied alloy. Results show that this process can provide a Ti6Al4V ELI alloy with a better Yield Strength (YS)/uniform deformation (εu) ratio and improved high cycle fatigue strength than those observed in the current microstructure used in medical implants. Lastly, cytotoxicity tests were performed on two types of human cells, namely MG63 osteoblast-like cells and fibroblasts. The results reveal the non-toxicity of the heat-treated Ti6Al4V ELI alloy.

Vascular endothelial growth factor in monochorionic twins with twin-twin transfusion syndrome.

OBJECTIVE: The purpose of this study was to determine vascular endothelial growth factor (VEGF) concentrations in the donor and the recipient in monochorionic twin pregnancies with twin-twin transfusion syndrome (TTTS) and single pregnancies in order to investigate the involvement of VEGF in the pathophysiology of TTTS. METHODS: Six twin pregnancies in 11 monochorionic twin pregnancies complicated with TTTS and 11 single control pregnancies were compared. Gestational age-matched fetal blood and placental samples were obtained at birth. Serum VEGF concentration in the umbilical vein was measured by an enzyme-linked immunoabsorbant assay. Tissue protein expression of VEGF was determined by using immunohistochemistry. Western blot analysis and scanning densitometry were used to quantify and compare the VEGF expression in the terminal villi. RESULTS: Serum VEGF concentrations in the umbilical vein in both donors and recipients tended to be higher than those in the controls. Immunolocalization of VEGF in terminal villous placenta samples in both donors and recipients was mainly observed in the syncytiotrophoblastic layer and vascular endothelial cells with less intense staining in stromal cells. The expression of VEGF in the donor placenta increased significantly (p=0.006) compared to that in the control placenta, but the expression of VEGF in the recipients tended to be higher than in the controls. CONCLUSION: Intrauterine circulatory imbalance may induce changes in VEGF expression and these alterations may be involved in both donor and recipient in the pathogenesis of TTTS, due to the maintenance of hemodynamic stability between the circulation of the twins.

Non-contact determination of arterial blood pressure alterations induced by blood loss using laser irradiation on the common carotid artery.

In order to avoid the secondary exposure of medical personnel to toxic materials under biochemical hazard conditions, we have reported a method for non-contact monitoring of heart and respiratory rates, using microwave radar or laser irradiation. In large-scale disasters, it is important to be able to diagnose shock without touching patients. We evaluated a non-contact method of monitoring arterial blood pressure alterations of New Zealand rabbits induced by blood loss, using He-Ne laser reflection on the common carotid artery. PVR was significantly correlated with systolic blood pressure (r = 0.95, p < 0.01), where PV = peak voltage of reflected laser amplitude, and PVR = PV(present moment state)/PV(normal state). The following formula was derived using the least-squares linear fitting: SBP = 69.6 PVR + 8.2, in which SBP is the systolic blood pressure. Before blood withdrawal, the mean blood pressure, heart rate and haematocrit were 68 +/- 3 mmHg, 154 +/- 10 bpm and 40 +/- 2%, respectively. After intervention, the mean blood pressure, heart rate and haematocrit were 38 +/- 5 mmHg, 197 +/- 25 bpm and 30 +/- 2%, respectively. The proposed non-contact method appears promising for future clinical application in determining arterial blood pressure alterations. It is likely to be useful in reducing the risk of secondary exposure to toxic chemicals or infectious organisms in the case of large-scale disasters.