Vortioxetine Treatment for Depression in Alzheimer’s Disease:A Randomized, Double-blind, Placebo-controlled Study

Objective@#Vortioxetine, a new antidepressant, has been demonstrated to have effects on depression and cognitive function. This study aimed to investigate the anti-depressive efficacy of vortioxetine through a well-designed double-blind, placebo-controlled study in Alzheimer’s disease (AD) patients, and to confirm the presence of secondary benefits, including the improvement of cognitive function and activities of daily living (ADL). @*Methods@#The present study included 100 AD patients with depression who were assigned randomly to 12 weeks of daily treatment with either vortioxetine or placebo. The primary efficacy measure was the change in the Cornell Scale for Depression in Dementia score from baseline to 12 weeks. Several secondary efficacy measures were evaluated, including the Korean version of the Short form of Geriatric Depression Scale and several cognitive function domains. The safety and tolerability of vortioxetine were also assessed. We performed modified intention-to-treat analysis using mixed modeling (the Mixed Models for Repeated Measures). @*Results@#There was no statistically significant difference between the two groups in terms of depressive symptoms, cognitive functions, and ADL. Further, the percentage of adverse events and drug discontinuation between the vortioxetine and placebo groups was similar. @*Conclusion@#Our results suggest that vortioxetine might not be effective in reducing depressive symptoms or cognitive impairment in AD patients with depression. However, general drug tolerance and patient safety were similar to those of placebo. Thus, additional studies are needed to replicate the effectiveness and tolerability of vortioxetine in AD patients with depression.

LB30057, a Direct Thrombin Inhibitor, the Effect of Restenosis in Porcine Coronary Injury Model

BACKGROUND AND OBJECTIVES: In a previous study, LB30057 was found to inhibit smooth muscle cell proliferation in a dose dependent manner, and prolonged 1 4-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in a rat carotid balloon injury model. The prolonged administration of LB30057, an orally active direct thrombin inhibitor, was evaluated and found to be a potential inhibitor of restenosis in a porcine coronary injury model. MATERIALS AND METHODS: An oversized balloon injury and a stent injury were given to the right coronary artery and left anterior descending artery, respectively, in the porcine model. LB30057 (50mg/kg) or a placebo was administrated for 28 days, using an osmotic pump, starting 6 hours prior to the injury until sacrifice on the 28th day. The drug concentration and antithrombotic effects (aPTT, thrombin-anti thrombin complex levels) were measured, and a histo-morphometric analysis performed 28 days later. RESULTS: The drug concentrations were 271+/-1 24 and 67+/-52 ng/mL on days 1 and 28 after injury in the drug group. The TAT (thrombin-antithrombin complex) levels were significantly lower in the drug than the control group on the 2nd and 7th days after injury (p<0.05). There were no significant differences in the injury scores, and the luminal, intimal and medial areas between the two groups. CONCLUSION: Prolonged administration of LB30057, using an osmotic pump, was not effective in reducing the restenosis in our pig coronary injury model.

Mitoxantrone Based Chemotherapy Regimen for Remission Induction in Children with Refractory Acute Myeloid Leukemia / 대한소아혈액종양학회지

PURPOSE: The effect of salvage chemotherapy using mitoxantrone based regimen for refractory AML (RAML) was analyzed. METHODS: Between January 1990 and March 2001, we treated 26 RAML. Ten patients received salvage chemotherapy with mitoxantrone based regimen and 16 patients with regimen devoid of mitoxantrone. RESULTS: Of total 54 AML patients treated during this period, 48 cases were available for analysis. RAML patients were 26 cases (54.1%) and M:F ratio was 2.3:1. FAB M2 and M4 were 8 each, and 7 cases were M7. There were 1 case of M1, M5 and M6 each. Eleven (42.3%) of them showed chromosomal abnormalities with variable karyotypes. Patients on mitoxantrone regimen all achieved complete remission (CR), while mitoxantrone devoid regimen achieved CR in only 56.2%. Allogeneic bone marrow transplantation was done in 5 cases (19.2%) of RAML, who are all alive with the median survival duration of 18 months. In mitoxantrone based regimen, 4 cases developed congestive heart failure and 5 had severe infection due to prolonged myelosuppression. In non-mitoxantrone group, 5 of 7 cases who failed to achieve CR died of sepsis. CONCLUSION: The mortality of RAML patients who are refractory to salvage chemotherapy remains very high. This study suggests that mitoxantrone based chemotherapy is effective in achieving complete remission as well as in prolonging survival in RAML patients.

A Case of de novo Interstitial Deletion of 17 Chromosome

This is the first reported case of a unique interstitial deletion involving the long arm of chromosome 17 in a Korean male infant born to parents with normal karyotype. The patient presented with multiple congenital malformations suggestive of chromosomal anomaly including round face, upslanted palpebral fissure, hypertelorism, posteriorly rotated low set ear, micrognathia, microcephaly, finger- like thumb, bilateral hearing loss, cryptorchidism, and severe developmental delay found upon outpatient follow-ups. A table of comparison is shown in between our case with previously reported 3 cases by Park, et al.(1992), Dallapiccola, et al.(1993), and Khalifa, et al.(1993).

A Case of Disseminated Lymphangiomatosis Involving Mediastinum, Bone, Spleen and Retroperitoneum in an Asymptomatic Healthy Child

Lymphangiomatosis, a benign tumor consisting of a cluster of dilated lymphatic channels, is very unusual. Most lymphangiomatoses are found in the neck and head area. Less than 5% are diagnosed intraabdominally and they are very infrequently encountered in the retroperitoneal area. Herein, we report a rare case of asymptomatic lymphangiomatosis of a 13 year-old boy during a routine chest radiologic exam at school who had disseminated lymphangiomatosis involving anterior mediastinum, multiple bone, spleen and retroperitoneum, which presented occasionally.

LB30057, A Direct Thrombin Inhibitor, Inhibits Vascular Smooth Muscle Cell proliferation in vitro and the Neointimal Hyperplasia in Rat Carotid Injury Model

BACKGROUND: Recent data showed prolonged administration of direct thrombin inhibitor might be needed to counteract the persistent thrombin activity and reduce the neointimal hyperplasia after arterial injury. We hypothesized that prolonged administration of LB30057, orally active direct thrombin inhibitor, might inhibit the vascular smooth muscle cell (SMC) proliferation in vitro and neointimal hyperplasia in rat carotid injury model. METHODS: In phase I, thrombin stimulated [methyl-3H] thymidine uptake was measured after LB30057 administration in cell culture study using rat aortic SMC. In phase II, LB30057 (low-dose: 5mg/kg, bid: mid-dose: 25mg/kg, bid: high-dose: 50mg/kg, bid) or placebo was administrated orally twice a day starting from 30minutes before injury until sacrifice for 14days in separated 2 sets of experiment. The histo-morphometric analysis for lumen area, intimal area, medial area, intima-to-medial ratio was performed. RESULTS: In vitro rat aortic SMC culture study, LB30057 inhibited thrombin-induced thymidine uptake. The mean neointimal area was significantly less in high-dose and mid-dose group than placebo group (high-dose vs. placebo: 0.14+/-0.02mm2 vs. 0.25+/-0.02mm2: mid-dose vs. placebo: 0.16+/-0.02mm2 vs. 0.29+/-0.03mm2, p<0.005) respectively and the mean ratio of neointima to medial area were significantly less in high-dose and mid-dose group than in placebo group (high-dose vs. placebo: 1.20+/-0.57 vs. 1.94+/-0.67, mid-dose vs. placebo: 1.58+/-0.29 vs. 2.39+/-0.27, p<0.05). There was no significant difference in the mean area of internal elastic lamina, external elastic lamina and mean luminal area between groups. In 2nd set experiment, the mean neointimal area (placebo: 0.29+/-0.03mm2, mid-dose: 0.16+/-0.02mm2: p<0.005), the mean area of internal elastic lamina and external elastic lamina were significantly less in mid-dose group than in placebo group. The mean ratio of neointima to medial area was significantly less in mid-dose group(1.58+/-0.29) than in placebo group (2.39+/-0.27) (p<0.05). CONCLUSION: LB30057 inhibits SMC proliferation in a dose dependent manner. Prolonged 14-day oral administration of LB30057 is effective in reducing the neointimal hyperplasia in rat carotid balloon injury model.