Conradi–Hünermann–Happle syndrome with abnormal lamellar granule contents

Background Long‐term maintenance treatment with 0·1% tacrolimus ointment for the prevention of flares has been demonstrated to be well tolerated and effective in adults for the treatment of atopic dermatitis (AD) but its impact on health‐related utility has not been reported. Objectives The purpose of this study was to estimate utility changes associated with the use of tacrolimus ointment in the maintenance treatment of adults with AD. Methods Data were collected from a clinical trial investigating long‐term maintenance treatment with 0·1% tacrolimus ointment in adults with AD. All patients were treated with twice‐daily tacrolimus ointment during an open‐label period (OLP) of up to 6 weeks, with subsequent randomization to a double‐blind disease‐control period (DCP) of 12 months comparing tacrolimus ointment, used twice weekly as maintenance treatment, vs. the emollient vehicle as standard treatment. Health‐related utility (EQ‐5D_index) was estimated by Monte Carlo simulation from SF‐12 responses by application of a published response mapping algorithm and the U.K. tariff for EQ‐5D responses and SF‐6D responses, respectively. Results Evaluable data were available for 257 patients stratified into mild, moderate or severe AD with a median age at screening of 28 years [interquartile range (IQR) 22–38] and 40% male. At screening the median EQ‐5D_index across the strata was 0·848 units (IQR 0·704–0·882) for mild cases, 0·796 (0·737–0·876) for moderate cases, and 0·760 (0·661–0·823, P < 0·001) for those with severe disease. At the end of the OLP, mean utility improvement across all strata was 0·027 [95% confidence interval (CI) −0·011 to 0·065, P = 0·165] for mild cases, 0·046 (95% CI 0·015–0·064, P = 0·002) for moderate cases and 0·076 (95% CI 0·035–0·118, P < 0·001) for those with severe disease. At the end of the blinded DCP, repeated measures analysis showed an age‐ and sex‐adjusted mean change of 0·045 units (P < 0·001) for subjects treated with tacrolimus ointment over those treated with emollient vehicle. Conclusions Patients with AD of all severities showed considerable decrements in health‐related utility. However, treatment with 0·1% tacrolimus ointment was associated with clinically significant improvement in health‐related utility for patients with moderate and severe AD, which was sustained over a 12‐month maintenance period compared with those using standard treatment with an emollient vehicle.     

Mechanism of inhibitory action of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) in vitro: effect of tranilast on the release of arachidonic acid and its metabolites

We investigated the mechanism of inhibitory action of tranilast, one of the anti-allergic drugs, on the release of slow reacting substance of anaphylaxis (SRS-A). Ionophore A23187 (0.5 or 0.2 micrograms/ml)-induced SRS-A release from rat peritoneal exudate cells (PEC) or human leucocytes was inhibited by tranilast (10(-5)-10(-3) M). The IC50 (the concentration which gives 50% inhibition) of tranilast on these reactions was approx. 10(-4) M. Prostaglandin (PG)E2 release from sensitized purified rat mast cells (PMC) by a specific antigen (DNP-Ascaris) was markedly suppressed by tranilast (10(-3) M). Similarly, ionophore A23187-induced PGE2 and 6-keto-PGF1 alpha releases from rat PEC were inhibited by tranilast (10(-5)-10(-3) M). DNP-Ascaris antigen-induced 3H-arachidonic acid (AA), 3H-PGE2, 3H-PGF2 alpha and 3H-PGD2 releases from rat PMC were markedly suppressed by tranilast (10(-5)-10(-3) M), DSCG (10(-5)-10(-4) M) and mepacrine (10(-3) M). The activity of AA-converting enzymes such as 5-lipoxygenase, cyclooxygenase, PGI2 synthetase, and glutathione-S-transferase was hardly influenced by tranilast (10(-5)-10(-3) M). From these results, we suggest that the mechanism of the inhibitory action of tranilast on the release of SRS-A is related to the processes prior to dissociation of AA from the membrane phospholipids.     

Management of acute aortic dissections with a cylinder-type balloon catheter to close the entry

Despite recent advances in medical treatment, an acute aortic dissection is still now often fatal because of the seriousness of its condition. The currently available therapies include blocking the progress of dissection with intensive drug therapy, a process leading to the chronic stage. However, the dissection often proceeds rapidly and may result in death. Various surgical procedures have been attempted so far, but they produce highly invasive stress and high risks. Accordingly, we designed a cylinder-type balloon catheter and developed a new closing procedure, wherein a balloon catheter is introduced and inflated at the site with an intimal tear to maintain the blood flow to the distal vessels and also to close the entry. With this procedure, the complaints will be relieved or disappear, the progress of the dissection can be stopped, and the blood flow can be restored to the reduced and collapsed true lumen. When the blood in the pseudolumen becomes coagulated and organized, the balloon is removed. If this catheter is introduced from the femoral artery (similar to an intra-aortic balloon pumping method), the invasive stress will be further reduced. This method appears to be the most useful for DeBakey type III dissections. We are now intensively studying the safe and effective application of this balloon catheter under various clinical conditions.     

Study of the mechanism of inhibitory action of tranilast on chemical mediator release

We investigated the mechanism of inhibitory action of tranilast on chemical mediator release by antigen-antibody reactions. Tranilast (10(-5)-10(-3) M) inhibited antigen (DNP-Ascaris)-induced histamine release from sensitized purified rat mast cells (PMC), but did not show an obvious influence on intracellular cyclic AMP. 45Ca uptake into PMC induced by antigen (300 micrograms/ml) was obviously suppressed by tranilast (10(-6)-10(-3) M). Tranilast (10(-4) M) inhibited antigen-induced histamine release from and 45Ca uptake into PMC independently of the presence or absence of glucose in the medium. On the other hand, 2-deoxyglucose (10(-2) M) markedly inhibited both responses in the absence but not in the presence of glucose. Tranilast slightly inhibited Ca-induced contraction of guinea pig taenia coli, but had no influence on aggregation of rabbit platelets. Verapamil (10(-6)-10(-4) M) had no effect on antigen-induced histamine release, but it markedly suppressed Ca-induced contraction and platelet aggregation. From these results, we suggest that the mechanism of inhibitory action of tranilast on the release of antigen-induced chemical mediator from mast cells involves the suppression of Ca uptake, but that its mode of action is apparently different from those of 2-deoxyglucose and verapamil.     

Two novel mutations of the retinitis pigmentosa GTPase regulator gene in two Chinese families with X-linked retinitis pigmentosa

目的：检测引起两个中国家系产生X连锁视网膜色素变性的RPGR基因突变。方法：以人类基因组DNA为模板,用位于内含子的引物扩增出RPGR基因外显子1-19的PCR片段。PCR产物经SSCP分析后直接进行测序。通过比较病人和正常人相应的DNA顺序,检出基因突变位点。结果：在两个家系检测到两个新突变c1536delC和E332X,它们分别位于RPGR基因的第12和第9外显子（这是两个外显子首次发现的突变）。两突变均可导致翻译提前终止,产生不具备正常功能的截短蛋白。结论：两个突变是相应空系产生视网膜色素变性的遗传学基础,所得结果有助于分析RPGR蛋白功能。