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Background-The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. Methods and Results-Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684Ϯ549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1Ϯ0.7 to 1.5Ϯ1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. Conclusions-In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Waon therapy is safe, improves clinical symptoms and cardiac function, and decreases cardiac size in CHF patients. Waon therapy is an innovative and promising therapy for patients with CHF.

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Protein S-K196E mutation as a genetic risk factor for deep vein thrombosis in Japanese patientsDeep vein thrombosis (DVT) is a multifactorial disease caused by interactions between acquired risk factors and coagulation abnormalities. 1 In whites, the factor V-Leiden and the prothrombin-20210GϾA are widely recognized as genetic risk factors for DVT. However, these 2 mutations are not present in Japanese populations, and little is known about the genetic risk factors for DVT in these populations. In this study, we evaluated the genetic contributions of 5 polymorphisms in Japanese DVT patients. The plasminogen-A620T mutation, formerly referred to as plasminogen-Tochigi, and the protein S-K196E mutation, formerly referred to as protein S-Tokushima, exhibited decreased activities of plasminogen and protein S despite normal antigen levels. 2-4 The ADAMTS13-P475S mutation exhibited low von Willebrand factorcleaving activity in vitro. 5 The factor XII-4CϾT substitution in the 5Ј-untranslated region, formerly referred to as 46CϾT, showed decreased plasma levels of both antigen and activity. 6 The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism is related to in vitro differences in transcription activity. 7 We genotyped subjects for these 5 polymorphisms and compared their genotypic frequencies between 161 DVT patients and 3655 population-based controls. The protocol for this study was approved by the ethical review committee, and only those subjects who provided written informed consent for genetic analyses were included in this study. All participants of this study were Japanese. The controls were from a general population randomly selected from the residents of Suita City located in the second largest urban area in Japan (the Suita Study). 8 One hundred sixty-one DVT patients, 78 men and 83 women, were registered by the Study Group of Research on Measures for Intractable Diseases, working under the auspices of the Ministry of Health, Labor, and Welfare of Japan. Six centers (Tochigi, Tokyo, Nagoya, Kyoto, and 2 in Osaka) participated in this study. The patients' mean age was 49.5 years (range, 12-87 years) and their mean body mass index was 23.6 Ϯ 3.3. Thirteen percent of patients had a family history of thrombosis, and 16% of the patients had recurrent thrombosis.Of all the polymorphisms tested, only the frequency of protein S-K196E was statistically different between the 2 groups ( 2 ϭ 38.3, P Ͻ .001) ( Table 1). No other frequency differences were statistically significant. Two DVT patients were homozygous for the protein S-196E allele; however, no homozygotes were identified in the control group. One patient with the 196EE genotype first developed DVT following surgery at age 47, while the other patient developed DVT during pregnancy at age 32.The mutant protein S with the E allele has already been intensively studied as protein S-Tokushima. 11 The protein S mutant showed the reduced activated protein C cofactor activity compared with wild-type protein S, suggesting a direct link between the protein S-...