Induction of Ph-negative normal clone and long-term survival by combined treatment with G-CSF plus middle dose cytosine arabinoside for patients with chronic myeloid leukemia in blastic transformation

Three patients with chronic myeloid leukemia (CML) in blastic transformation were treated with G-CSF plus middle dose cytosine arabinoside (Ara-C). G-CSF was administered (150 mg, s.c. or 300 mg, d.i.v./day) 24 hr prior to Ara-C (2-3 g/body, 6 hour d.i.v. for 2-5 days) and continued until the peripheral neutrophil count rose above 1,000/microlitre. As a supplement, VP-16 (80 mg/m2, for 2 days) was administered as warranted to control the growth of blastic cells. All 3 patients survived for more than 12 months with a favorable performance status. Normal karyotypes were detected in 2 of the patients after chemotherapy. One of those patients in paticular demonstrated normal bone marrow findings with the almost complete disappearance of the Ph-positive clone. In vitro cultures of peroxidase-negative CML blastic cells revealed that G-CSF stimulated the induction of blastic cells into the cell cycle and that blastic cell apoptosis was more pronounced in cells cultured with G-CSF plus Ara-C than with G-CSF or Ara-C alone. G-CSF plus middle dose Ara-C therapy appears to be a strong candidate for the treatment of CML in blastic transformation with a poor prognosis.     

Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism: results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research.

The incidence of acute pulmonary thromboembolism (APTE) in Japan is quoted as being extremely low compared with the United States, and the incidence and clinical characteristics of chronic pulmonary thromboembolism (CPTE) in Japan is unknown, so this study investigated these aspects of CPTE in 309 patients with APTE and 68 patients with CPTE. The ratio of the incidence of CPTE to APTE was 0.22 and there was no significant difference in age or sex between the APTE and CPTE patients. All of the predisposing factors for pulmonary thromboembolism, except for thrombophilia, were more frequently seen in the patients with APTE. There are some differences in the incidence and clinical characteristics of CPTE compared with APTE between Japanese and American patients in Japan, suggesting that the pathogenesis of CPTE in Japan may differ from that in the USA.     

Estimated numbers of patients with intractable respiratory diseases]

To estimate the number of patients with intractable respiratory diseases, we conducted a two-stage nationwide epidemiological survey in 1997. The first survey was performed at randomly sampled hospitals to identify the number of patients treated. The second survey sought detailed clinico-epidemiological data on the patients reported in the first survey. The response rates were 54% for the first survey and 62% for the second. Based on the survey findings, we derived the following nationwide estimates: 450 patients (95% confidence interval: 360-530) with chronic thromboembolic pulmonary hypertension; 230 (200-260) with primary pulmonary hypertension; 180 (150-210) with obesity-associated hypoventilation syndrome; 40 (30-50) with primary alveolar hypoventilation syndrome; 160 (140-180) with histiocytosis X; and 190 (150-230) with juvenile pulmonary emphysema.     

Specific gastroduodenoscopic findings in Crohn''s disease: Comparison with findings in patients with ulcerative colitis and gastroesophageal reflux disease

BACKGROUND: Crohn's disease patients often carry gastroduodenal lesions. However, few reports have addressed specific gastroduodenoscopic findings in Crohn's disease patients. METHODS: The gastroduodenoscopic findings of 63 Crohn's disease patients were examined. Those of 62 ulcerative colitis and 63 age- and gender-matched gastroesophageal reflux disease patients were also reviewed as controls. Findings of bamboo-joint-like appearance, gastric antral erosions, and duodenal lesions were the specific findings that were highlighted. RESULTS: Of 63 Crohn's disease patients, 47 (75%) had at least one of the specific gastroduodenoscopic findings, and the prevalence of these findings was significantly higher in Crohn's disease patients than in ulcerative colitis and gastroesophageal reflux disease patients (ulcerative colitis, 24/62, 39%; gastroesophageal reflux disease, 15/63, 24%, P < 0.0001). In particular, bamboo-joint-like appearance was almost unique to Crohn's disease patients (Crohn's disease, 28/63, 44%; ulcerative colitis, 3/62, 5%; gastroesophageal reflux disease, 0/63, 0%, P < 0.0001). Analysis of the relationship between the Crohn's disease patient's background and gastrodunodenoscopic findings revealed that both patients with disease affecting the ileum and those with previous gut operations were more likely to exhibit the specific gastroduodenoscopic findings (P = 0.030 and P = 0.043, respectively). CONCLUSION: Specific gastroduodenoscopic findings were observed in Crohn's disease patients. In particular, bamboo-joint-like appearance could be a unique marker of Crohn's disease.     

Lymphoid crisis with T-cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia

A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte-rosetting-, Leu-1+, Leu-5+, OKT-4+, OKT-8+, common ALL antigen-, HLA-DR-, cytoplasmic and surface immunoglobulin-, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase-, indicating T-cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T-cell characters: dot-positivity for acid phosphatase and beta-glucuronidase, and negative for acid alpha-naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T-lineage.     

A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: A population-based,cross-sectional analysis

BackgroundEnhanced oxidative stress or defective anti-oxidant defenses are related to the pathogenesis of depressive symptoms. Lycopene is the most powerful antioxidant amongst the carotenoids. The aim of this study was to investigate the relationship between different vegetables, including tomatoes/tomato products (a major source of lycopene), and depressive symptoms in a community-based elderly population.MethodsWe analyzed a cross-sectional survey including 986 community-dwelling elderly Japanese individuals aged 70 years and older. Dietary intake was assessed using a valid self-administered diet-history questionnaire, and depressive symptoms were evaluated using the 30-item Geriatric Depression Scale with 2 cut-off points: 11 (mild and severe) and 14 (severe) or use of anti-depressive agents.ResultsThe prevalence of mild and severe and severe depressive symptoms was 34.9% and 20.2%, respectively. After adjustments for potentially confounding factors, the odds ratios of having mild and severe depressive symptoms by increasing levels of tomatoes/tomato products were 1.00, 0.54, and 0.48 (p for trend <0.01). Similar relationships were also observed in the case of severe depressive symptoms. In contrast, no relationship was observed between intake of other kinds of vegetables and depressive symptoms.LimitationsThis is a cross-sectional study, and not for making a clinical diagnosis of depressive episodes.ConclusionsThis study demonstrated that a tomato-rich diet is independently related to lower prevalence of depressive symptoms. These results suggest that a tomato-rich diet may have a beneficial effect on the prevention of depressive symptoms. Further studies are needed to confirm these findings.     

Effects of Helicobacter pylori eradication therapy on hyperammonaemia in patients with liver cirrhosis.

BACKGROUND AND AIMS: Helicobacter pylori has strong urease activity. Ammonia produced by H pylori in the stomach can be a source of systemic ammonia in patients with hepatic dysfunction. The effect of the eradication of H pylori on hyperammonaemia was examined in patients with liver cirrhosis. SUBJECTS AND METHODS: Ammonia concentrations in blood and gastric juice were analysed in 50 patients with liver cirrhosis and hyperammonaemia. All patients were first treated with a low protein diet, kanamycin, lactulose, and branched chain enriched amino acid solution. Hyperammonaemia remained in 18 patients. These 18 patients were divided into three groups according to the status of H pylori infection; those with a diffuse distribution of H pylori in the stomach (group I), those with a regional distribution (group II), and those without H pylori (group III). These patients were given 30 mg iansoprazole, 1000 mg amoxicillin, and 400 mg clarithromycin or 500 mg metronidazole for two weeks to eradicate H pylori. RESULTS: In group I ammonia concentrations in blood and gastric juice were significantly reduced after H pylori eradication. The blood ammonia concentration at 12 weeks after the eradication was still significantly lower than that before eradication. In groups II and III the ammonia concentrations in blood and gastric juice were not significantly reduced after eradication therapy. CONCLUSIONS: The diffuse distribution of H-pylori in the stomach contributes partly to hyperammonaemia in patients with liver cirrhosis, and the eradication of H pylori is effective in patients with hyperammonaemia with diffuse H pylori infection in the stomach.     

Modifiable factors for the length of life with disability before death: mortality retrospective study in Japan

BACKGROUND: Past studies have measured and described the length of life with disability before death, but there has been no study of the relationship between modifiable lifestyle factors and duration of disability. OBJECTIVE: To examine whether there are modifiable factors influencing the length of life with disability before death. METHODS: The study was designed as a retrospective observation of the deceased who had earlier been enrolled in a prospective cohort study.During the follow-up period (1996-1999), we documented 781 deaths among those who were 70-79 years of age at the baseline survey in 1994 (n=10,216). In 2000, we interviewed family members of the deceased about the duration of the subjects' disability before death (n=655). RESULTS: The median duration of disability before death was approximately 6 months. Both higher Body Mass Index (BMI) and shorter time spent walking were significantly associated with an increased risk of long-term disability (more than 6 months). The odds ratios of long-term disability were 1.3 in those with BMI 20-25 and 2.1 in those with BMI>25, compared with BMI<20. The odds ratios of long-term disability were 1.3 in those walking for 0.5-0.9 h/day and 1.7 in those walking for <0.5 h/day, compared with those walking for >1.0 h/day. These relationships were unchanged after stratification for causes of death. CONCLUSION: Weight control and walking in later life may shorten the length of life with disability before death.     

Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression

BACKGROUND/AIMS: Chemoprevention should be a promising approach to improve the prognosis of the patients with hepatocellular carcinoma (HCC). Angiogenesis is now recognized as a crucial step not only in tumor growth, but also in early carcinogenesis. The aim of this study was to elucidate the combination effect of the clinically used vitamin K(2) (VK) and the angiotensin-converting enzyme inhibitor, perindopril (PE), on hepatocarcinogenesis, especially in conjunction with angiogenesis. METHODS: In a diethylnitrosamine-induced rat hepatocarcinogenesis model, the effects of VK and PE on the development of liver enzyme-altered preneoplastic lesions and angiogenesis were examined. RESULTS: Treatment with both VK and PE markedly inhibited the development of preneoplastic lesions in association with suppression of neovascularization in the liver. The combination treatment with VK and PE exerted a more potent inhibitory effect as compared with the single agent treatments. The in vitro study demonstrated that VK and PE inhibited the endothelial cell (EC) tubular formation. VK also suppressed the EC proliferation in a dose-dependent manner. CONCLUSIONS: The combination of VK and PE exerted a chemopreventive effect against rat liver carcinogenesis via suppression of angiogenesis. Since both agents are widely used in the clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against HCC in the future.