A 48-year-old man with Buerger disease and intractable finger ulcers underwent successful transplantation of autologous peripheral blood-derived mononuclear cells pretreated with erythropoietin and blood donation to activate bone marrow function. Clinical symptoms on his finger ulcers improved significantly within 1 month after mononuclear cell transplantation, however, one of the intractable ulcers reappeared 2 months later. In total three transplantations were performed. Every cell transplantation revealed similar effectiveness 1 month later, and the interval of the subsequent disappearance of finger ulcers ranged from 3–6 months. There were no adverse effects based on this new therapy. These findings suggest that autologous peripheral mononuclear cell transplantation pretreated with erythropoietin and blood donation might be a non-invasive and safe alternatives for patients with Buerger disease and intractable finger ulcers.

Objective : Carvedilol is a non-selective β blocker with an α blocking activity. Since this drug is highly fat-soluble, it can pass through the blood-brain barrier, and thus may induce depression and lower QOL. In the present study, physicians and pharmacists collaborated to evaluate the antihypertension effect of carvedilol and post-administration changes in QOL. Furthermore, the relationship between QOL and antihypertension effect was analyzed.
Design : Self-controlled study.
Patients and Methods : Subjects were outpatients with hypertension above the age of 70 years who visited one of 42 medical institutions in Japan between April 1995 and March 1996. A total of 243 patients were registered, and 10-20 mg of carvedilol was administered once a day for six months. Pharmacists assessed the QOL of these patients by asking 82 questions on three separate occasions : before administration and one and six months after administration. The antihypertensive effect of this drug was investigated in patients in whom all three QOL questionnaires were collected. The main test items were antihypertensive effect, changes in QOL (subjective QOL with a special emphasis on patient psychology), and the relationship between antihypertensive effect and QOL. The antihypertensive effect of this drug was statistically analyzed by a paired t-test, and changes in QOL were statistically analyzed using generalized estimating equations.
Results : All three QOL questionnaires were collected from a total of 146 patients. Their pre-administration systolic blood pressure was 159.6±1.4 mmHg, and diastolic blood pressure 94.0±0.9 mmHg, and their blood pressure decreased significantly one month after the start of administration. This antihypertensive effect of carvedilol persisted, and the systolic and diastolic blood pressure of these patients six months after the start of administration was 141.1±1.2 and 85.2±0.7 mmHg, respectively (significant decreases when compared to pre-administration levels ; both p<0.05).
Subjective QOL improved significantly after carvedilol administration. And, changes were not seen in sexual function. Changes in the five categories of subjective QOL were as follows : psychological stability, disease-induced inconvenience, and independence improved significantly after carvedilol administration, but changes were not seen in gratification or vitality. However, improvements in subjective QOL did not correlate with improvements in blood pressure.
Conclusions : The results of the present study showed that carvedilol improved QOL without negatively affecting sexual function. Subjective QOL reflects the psychological well-being of patients. In the present study, psychological stability, disease-induced inconvenience, and independence improved significantly, but changes were not seen in gratification or vitality. Since β blockers can suppress the central nervous system, they can reduce psychological stability, gratification and vitality. Even though carvedilol is highly fat-soluble, the results of non-clinical studies have shown that it does not suppress the central nervous system as much as propranolol. The results of the present study showed that carvedilol does not strongly suppress the central nervous system of humans. Moreover, significant changes in QOL were not seen between one and six months after the start of administration of carvedilol, suggesting that it is possible to estimate the QOL of patients on antihypertensive therapy after six months of administration by assessing their QOL one month after administration.

We investigated the possible association between genetic polymorphisms in the dopamine receptor and serotonin transporter genes and the responses of schizophrenic patients treated with either risperidone or perospirone. The subjects comprised 27 patients with schizophrenia who were clinically evaluated both before and after treatment. The genotyping of the polymorphisms of the dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene (5HTT)(variable number of tandem repeats; VNTR) were performed using the real-time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were no significant correlations between clinical response and polymorphism in the case of risperidone, and for perospirone treatment it was impossible to analyze the clinical evaluation due to the absence of genotype information. On the other hand, in DRD4 there were significant correlations in the two-factor interaction effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample represents a serious limitation, these results suggest that variants in DRD4 are a predictor of whether treatment will be more effective with risperidone or with perospirone in individual patients.
Genotype ; Hand ; Humans ; Isoindoles ; Polymorphism, Genetic ; Real-Time Polymerase Chain Reaction ; Receptors, Dopamine ; Receptors, Dopamine D2 ; Receptors, Dopamine D4 ; Risperidone ; Schizophrenia ; Serotonin Plasma Membrane Transport Proteins ; Tandem Repeat Sequences ; Thiazoles

Objectives: To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). Methods: This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. Results: Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. Conclusions Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.

Objectives: To compare the effect of eldecalcitol and alfacalcidol on skeletal microstructure by highresolution peripheral QCT (HR-pQCT). Methods: This was a substudy of a randomized, double-blind, active comparator trial. Five female osteoporotic patients with 1-year 0.75 mg/day eldecalcitol and 5 with 1-year 1.0 mg/day alfacalcidol completed HR-pQCT scans before and after treatment were enrolled. Results: Total vBMD [1.67 ± 1.06% (mean ± SD), P ¼ 0.043 versus baseline] and trabecular vBMD (2.91 ± 1.72%, P ¼ 0.043) at the radius increased in eldecalcitol group, while total, trabecular, and cortical vBMD tended to decrease in alfacalcidol group, with a significant reduction in cortical vBMD at the tibia (0.88 ± 0.62%, P ¼ 0.043). Cortical area (1.82 ± 1.92%, P ¼ 0.043) at the radius and thickness (0.87 ± 1.12%, P ¼ 0.043) at the tibia increased in eldecalcitol group, while these parameters decreased with alfacalcidol at the tibia (1.77 ± 1.72%, P ¼ 0.043 for cortical area; 1.40 ± 2.14%, P ¼ 0.042 for cortical thickness). Trabecular thickness at the radius (1.97 ± 1.93%, P ¼ 0.042) and number at the tibia (3.09 ± 3.04%, P ¼ 0.043) increased by eldecalcitol but did not increase by alfacalcidol. Trabecular separation decreased by eldecalcitol (2.22 ± 2.43%, P ¼ 0.043) but tended to increase by alfacalcidol at the tibia. Conclusions Eldecalcitol has the greater potential to improve cortical and trabecular microstructure at the peripheral bone than alfacalcidol which needs further more studies.

BACKGROUND: Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment. METHODS: A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.3+/-35.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively. RESULTS: After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 167+/-63 to 151+/-49 mg/dL (P<0.01), and from 7.5%+/-1.3% to 6.9%+/-0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease. CONCLUSION: Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment.
Blood Glucose ; Body Mass Index ; Coronary Artery Disease ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Dipeptidyl-Peptidase IV Inhibitors ; Hemoglobin A, Glycosylated ; Humans ; Retrospective Studies ; Treatment Outcome