Radiographic Prediction of the Results of Long-term Treatment with the Pavlik Harness for Developmental Dislocation of the Hip

In 1957, Pavlik introduced the Pavlik harness as a useful treatment for developmental dislocation of the hip (DDH), and subsequent studies have documented favorable outcomes among patients treated with this device. However, there are only a few articles reporting how early radiographic measurements can be used to determine the prognosis after treatment with the Pavlik harness. In this study, 217 hips from 192 patients whose DDH treatment with the Pavlik harness was initiated before they were 6 months old and whose follow-up lasted at least 14 years (rate, 63.8%) were analyzed using measurements from radiographs taken immediately before and after harness treatment, and at 1, 2, and 3 years of age. Severin's classification at the final follow-up was I or II in 71.9% and III or IV in 28.1% of the hips, respectively. Avascular necrosis of the femoral head (AVN) was seen in 10% of the hips. Stepwise multiple regression analysis was performed to retrospectively determine whether any radiographic factors were related to the final classification as Severin I/II or III/IV. Receiver opera-ting characteristic (ROC) curves were drawn for these factors, and a Wiberg OE angle (Point O was the middle point of the proximal metaphyseal border of the femur) of 2 degrees on the 3-year radiographs was found to be the most useful screening value for judging the acetabular development of DDH cases after treatment with a Pavlik harness, with a sensitivity of 71% a specificity of 93%, and a likelihood ratio of 10.1.</p

ADHD患児とその保護者の服薬アドヒアランス調査

【目的】注意欠如・多動症（ADHD）の患児とその保護者が薬物治療をどのように評価し，治療に向き合っているのかを明らかにする。【方法】ADHDの診断を受け，メチルフェニデート徐放剤およびアトモキセチンを処方された小１から高３までの患児94 人と保護者106人に質問紙調査と半構造化面接を行った。【結果】90％以上で服薬は規則正しく行われており，薬物治療に対する肯定的な評価は，患児・保護者で約80 ～ 90％と高かった。一方で，全面的に賛成しているわけではなく，約80％の保護者が否定的な意見も持っていた．否定的評価をする要因は，保護者は副作用を含めた長期的な影響への不安，患児は服薬の煩わしさや胃腸症状が多かった。定期的な薬物治療を続けているにも関わらず，効果と不安等を天秤にかけて治療を継続することへの積極的な支持は，患児・保護者で約50 ～ 60％であった。【結論】小児では，低年齢のため客観的に自身の状況を判断し，見通しをもって治療に参加することが難しい場合がある。患児へは胃腸症状への対処を，保護者へは治療の見通しや副作用について丁寧な説明を繰り返すことによって，薬物治療への否定的評価が軽減され，服薬アドヒアランスが向上する可能性がある

Effect of single-dose extended-release oral azithromycin on anticoagulation status in warfarinized patients

Objective. The aim of this study was to investigate the possible influence of single-dose 2.0-g azithromycin (AZ-ER) on anticoagulation in patients taking warfarin. Study Design. Eighteen consecutive patients receiving long-term stable warfarin therapy were enrolled in this study. AZ-ER was administered 1 hour prior to tooth extraction. The international normalized ratio (INR) value was measured prior to AZ-ER administration as well as during, 1 day after, and 7 days after the tooth extraction. Additionally, the azithromycin concentration in the extraction wound as well as in the peripheral venous blood was assessed. Results. The changes in INR throughout the study period were not statistically significant (2-factor analysis of variance, NS). The azithromycin concentration in extraction wounds was higher than that in peripheral veins. Conclusions. The results of this study suggest that prophylactic administration of AZ-ER to patients receiving daily warfarin therapy with a stable coagulation status has no relevant effect on the anticoagulant effect of warfarin. (Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:148-151)ArticleORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY. 115(2):148-151 (2013)journal articl

Structural variation in the glycogen synthase kinase 3β and brain‐derived neurotrophic factor genes in Japanese patients with bipolar disorders

Background: Lithium is the first‐line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3β and brain‐derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium. Method: Fifty patients with BDs and 50 healthy subjects (mean age 55.0 ± 15.0 years; M/F 19/31) participated. We examined structural variation of the GSK3β and BDNF genes by real‐time PCR. We examined the influence of structural variation of these genes on the therapeutic responses to lithium and the occurrence of antidepressant‐emergent affective switch (AEAS). The efficacy of lithium was assessed using the Alda scale, and AEAS was evaluated using Young Mania Rating Scale. Results: Although we examined structural variations within intron II and VII of the GSK3® gene and from the end of exon IV to intron IV and within exon IX of the BDNF gene, no structural variation was found in BDs. Whereas 5 of 50 patients exhibited three copies of the genomic region within exon IV of the BDNF gene, all healthy subjects had two copies. No difference in the therapeutic efficacy of lithium was found between patients with three and two copies. No difference in the occurrence of AEAS was found between the two groups. Conclusion: The amplification of the BDNF gene influenced neither the therapeutic responses to lithium nor the occurrence of AEAS

Thrombin Activates Ca2+-permeating Nonselective Cation Channels through Protein Kinase C in Human Umbilical Vein Endothelial Cells

We analyzed Ca-permeating nonselective cation channels (NSCs)mediating thrombin-induced contraction of human umbilical vein endothelial cells (HUVECs). A Ca chelater, BAPTA-AM (10μM), significantly inhibited the thrombin-induced contraction of HUVECs.Thrombin induced inward currents at -60 mV in the presence of intracellular MgATP. Removal of extracellular Caﾌﾞｸﾞsignificantly decreased the currents. A selective phospholipase C inhibitor, U73122 (1μM) but not its inactive analogue, U73343 (1μM) almost completely inhibited the currents. Neither a selective inhibitor of Caﾌﾞｸﾞ-ATPase of endoplasmic reticulum, thapsigargin (1μM)nor a diacylglycerol analogue, 1-oleoyl-2-acetyl-glycerol (30μM)activated the currents. However, a selective protein kinase C inhibitor, bisindolylmaleimide I (500 nM) significantly inhibited the currents.The thrombin-induced currents were significantly inhibited by SKF96365 (50μM)but not by La(1mM), ruthenium red (10μM) or flufenamic acid (100μM). As assessed with RT-PCR, HUVECs expressed transient receptor potential(TRP)M4,7,TRPV1,2,4,TRPC1,4 and 6 subunits of NSCs.These results indicate that thrombin activates Ca-permeating NSCs containing TRPC4 through protein kinase C in HUVECs. Thus,drugs specifically inhibiting TRPC4-containing channels might be effective to control fatal diseases such as sepsis where thrombin mediates the vicious cycle between inflammation and coagulation.Article信州医学雑誌 59(1): 13-26(2011)departmental bulletin pape

Characterization of autonomous Dart1 transposons belonging to the hAT superfamily in rice

An endogenous 0.6-kb rice DNA transposon, nDart1-0, was found as an active nonautonomous element in a mutable virescent line, pyl-v, displaying leaf variegations. Here, we demonstrated that the active autonomous element aDart in pyl-v corresponds to Dart1-27 on chromosome 6 in Nipponbare, which carries no active aDart elements, and that aDart and Dart1-27 are identical in their sequences and chromosomal locations, indicating that Dart1-27 is epigenetically silenced in Nipponbare. The identification of aDart in pyl-v was first performed by map-based cloning and by detection of the accumulated transposase transcripts. Subsequently, various transposition activities of the cloned Dart1-27 element from Nipponbare were demonstrated in Arabidopsis. Dart1-27 in Arabidopsis was able to excise nDart1-0 and Dart1-27 from cloned sites, generating footprints, and to integrate into new sites, generating 8-bp target site duplications. In addition to Dart1-27, Nipponbare contains 37 putative autonomous Dart1 elements because their putative transposase genes carry no apparent nonsense or frameshift mutations. Of these, at least four elements were shown to become active aDart elements in transgenic Arabidopsis plants, even though considerable sequence divergence arose among their transposases. Thus, these four Dart1 elements and Dart1-27 in Nipponbare must be potential autonomous elements silenced epigenetically. The regulatory and evolutionary implications of the autonomous Dart1 elements and the development of an efficient transposon-tagging system in rice are discussed

Cytochrome P450 3As Gene Expression and Testosterone 6 beta-Hydroxylase Activity in Human Fetal Membranes and Placenta at Full Term

Expression levels of cytochrome P450 (CYP) 3A4, CYP3A5 and CYP3A7 mRNAs in placentas and fetal membranes, which were split into amnion and chorion leave attached decidua (chorion/decidua), obtained from pregnant women with normal delivery (5 subjects) and Caesarean section (15 subjects) were determined. These CYP3A mRNAs were also expressed in amnion and chorion/decidua together with placenta, although the expression level of these mRNAs was strikingly different between subjects. The expression level of the CYP3A4 mRNA in the placenta was about 2-fold higher than those in amnion and chorion/decidua. On the other hand, the expression levels of CYP3A5 and CYP3A7 mRNAs were highest in chorion/decidua. The immunologically related protein(s) with CYP3A7 was detected in all tissues examined. Testosterone 6 beta-hydroxylase activity in homogenate of human placenta, amnion and chorion/decidua were 26.6, 3.7 and 4.6 pmol/h/mg protein, respectively. These results suggest that CVP3As in fetal membranes have the metabolic function to protect the fetus from exposure to drugs.ArticleBIOLOGICAL & PHARMACEUTICAL BULLETIN. 33(2):249-254 (2010)journal articl

Mechanisms of CYP3A Induction by Glucocorticoids in Human Fetal Liver Cells

Human fetal liver (HFL) cells express major drug metabolic enzymes CYP3A4, CYP3A5 and CYP3A7. In the fetal hepatocytes, betamethasone and dexamethasone (DEX) markedly enhanced the expression levels of CYP3A4 and CYP3A7 mRNAs and slightly increased the expression level of CYP3A5 mRNA. Interestingly, a high correlation between the CYP3A induction ability and the intensity of anti-inflammatory effect was observed. Human glucocorticoid receptor (GR) small interfering RNA clearly attenuated the expression level of GR mRNA, and diminished the DEX-stimulated CYP3A4, CYP3A5 and CYP3A7 expression in HFL cells. These findings indicate that GR mediates the induction of CYP3A4 and CYP3A7 expression in human fetal hepatocytes as well as the CYP3A5.ArticleDRUG METABOLISM AND PHARMACOKINETICS. 27(6):653-657 (2012)journal articl